Popular in Course
verified elite notetaker
Popular in Department
This 87 page Reader was uploaded by Corinne Caro on Monday October 5, 2015. The Reader belongs to a course at a university taught by a professor in Fall. Since its upload, it has received 6 views.
Reviews for Chapter-2The-Cell.pdf
Report this Material
What is Karma?
Karma is the currency of StudySoup.
Date Created: 10/05/15
Chapter 2 The Cell Structure and Function Biomolecules biomolecules 0 molecules that are synthesized by living organisms and contain carbon atoms 0 common biomolecules contain oxygen nitrogen hydrogen 0 biomolecules include carbohydrates lipids nucleotides protein carbohydrates 0 polar molecules dissolve in water 0 carbohydrates classi ed into monosaccharides disaccharides and polysaccharides monosaccharides are simple sugars composed of one single unit EX glucose an important source of energy for our cells fructose and galactose Disaccharides are carbohydrates formed by the covalent bonding of two monosaccharides EX sucrose composed on glucose and fructose AKA table sugar and lactose found in milk Polysaccharides are formed by covalent bonding of several monosaccharides EX glycogen a polymer of glucose subunits and is found in animal cells starch polysaccharide found in plants cellulose another polysaccharide found in plants 0 Synthesis and breakdown of saccharides Synthesis through condensation Condensation a type of reaction that links monosaccharides together 0 water is produced in the process breakdown through hydrolysis hydrolysis a reaction in which water splits the disaccharides or polysaccharides into their monosaccharide subunits o Lipids a diverse group of biomolecules that contain primarily a carbon and hydrogen atoms linked together by covalent bonds 0 Generally nonpolar molecules that do not dissolve in water 0 May sometimes contain other molecules making it polar amphipathic Amphipathic9 a molecule that contains both polar and nonpolar regions 0 5 main classes of lipids 1 triglycerides 2 ketones 3 phospholipids 4 eicosanoids 5 steroids 0 1 Triglycerides o 3 ph Composed of one glycerol molecule and three fatty acid molecules Glycerol threecarbon alcohol that functions as the backbone of triglyceride Fatty acid long chain of carbon atoms with a carboxyl group COOH at one end NONPOLAR Saturated no double bonds Unsaturated double bonds or more Triglycerides formed by linking each of the three fatty acids to a different carbon in the glycerol backbone NONPOLAR Nonpolar do not dissolve in water because of the presence of nonpolar carbontocarbon and carbon tohydrogen bonds ospholipid phospholipids lipids that contain a phosphate group consists of a glycerol backbone linked by two fatty acid chains and a phosphatecontaining group has a hydrophilic head polar and a hydrophobic tail nonpolar phospholipids are amphipathic molecules the polar region dissolves in water faces the water environment and nonpolar does not face each other forming hydrophobic interior forming bilayer core structure in cell membranes micelle a spherical structure composed of a single layer of phospholipids functions in the transport of nonpolar molecules in an aqueous environment surfacants another type of phospholipid found in thelungs o 4 eicosanoids eicosanoids9 modi ed fatty acids that function in intercellular communication polar molecules and include prostaglandins and thromboxanes o 5 steroids steroids threecarbon rings and one vecarbon ring most common is cholesterol 0 important component of plasma membrane and a precursor for the formation of bile salts for the liver as well as to steroid hormones testosterone estradiol cortisol and D3 amino acids and proteins 0 proteins polymers of amino acids relatively small biomolecules that contain a central carbon an amino group an R group hydrogen and carboxyl group 0 4 amino acids alanine tyrosine glutamate lysine 0 proteins play a role in intercellular communication 0 polymers are formed by joining two amino acids together using a peptide bond9 polypeptides they are called a peptide bond forms between the carboxyl group of one and the amino acid of another through condensann peptides short chains of amino acids less than 50 aminos proteins contain more than 50 protein structure includes primary secondary tertiary quaternary primary cord stretched out 0 normal sequence of amino acids secondary the coiled cord 0 folding pattern produced by hydrogen bonds between carboxyl and amino group 0 alpha and beta tertiary loops and bends in the coiled cord 0 folding produced by R groups 0 different interactions include hydrogen bonds ionic bonds van der Waals forces and covalent bonds 0 disul de bridges form in covalent and are important in antibodies and insulin quaternary existence of two cords wrapped together 0 exist only in proteins containing more than one polypeptide chain 0 ex hemoglobin 0 proteins can be classi ed into brous or globular brous elongated strand EX tropomyosin collagen globular irregular and bulkyEX receptors carrier proteins o lipoproteins found in blood and important in transport of lipids o glycoproteins carbohydrate attached important in cell recognition nucleotides and nucleic acid 0 nucleotides function in the transfer of energy within cells and form genetic material of cells 0 nucleotides contain 5carbon carbohydrate nitrogenous base and one phosphate groups carbohydrate is either deoxyribose or ribose nitrogenous base in nucleotides include two classes pyrimidines contain a single carbon ring and Cytosine Thymine and Uracil purines contain a double carbon rin and include Adenine and Guanine nucleotide monophosphate one phosphate diphosphate 2 triphosphate 3 several nucleotides play a role in energy exchange 0 polymers of nucleotides include nucleic acids Cell Structure function in storage and expression of generic info DNA deoxyribonucleic acid found in cell nucleus and RNA ribonucleic acid found in cell nucleus and cytosol both DNA double stranded and RNA single stranded are polymers of nucleotides bases in DNA A adenine G guanine C cytosine T thymine 3 carbohydrate ends and 5 phosphate end 0 double stranded and held together by bonding between bases by the law of complementary base pairing9 whenever two strands of nucleic acid are held together by hydrogen bonds G is paired with C and A with T of the opposite strand or A with U in RNA bases in RNA A adenine G guanine C cytosine U uracil synthesize RNA from DNA Each cell is bound by a plasma membrane 0 Plasma membrane separates the cell from the extracellular uid FUNCTION maintains boundary of cell anol integrity of cell structure embosses proteins serve multiple functions Inside the cell are 2 components 0 Nucleus membranebound structure that contains the genetic information FUNCTION houses DNA Which dictates cellular function anol protein synthesis 0 Cytoplasm includes everything inside the cell except the nucleus Consists of two parts Cytosol gellike intracellular uid Organelles structures made up of a variety of macromolecules that carry speci c functions 0 Membrane bound and nonmembranous FUNCTION cell metabolism storage Structure of the plasma membrane 0 Consists of phospholipids cholesterol proteins and carbohydrates Phospholipid bilayer o Membrane considered uid because the phospholipids and other molecules are not linked by chemical bonds and can move laterally 0 Cholesterol molecules found in lipid bilayer o Aquaporins found in membrane Aquaporins proteins that form pores in the membrane through which water passes o Membrane proteins 2 main proteins integral membrane proteins and peripheral membrane proteins Integral membrane proteins embedded within the lipid bilayer are amphipathic Transmembrane proteins type of integral protein that span the lipid bilayer and surface when exposed to both cytosol and extracellular uid 0 Include channels and carrier proteins proteins facing cytosol function as enzymes to catalyze chemical reaction or as receptors 0 Peripheral membrane proteins9 loosely bound to the membrane by associations with integral membrane proteins or phospholipids 0 Located on cytosolic surface and function as part of the cytoskeleton Membrane carbohydrates 0 Covalently bonded with membrane lipidsproteins to form glycolipids or glycoproteins o On extracellular surface and have 2 functions Form glycocalyx a protective layer that also functions in holding cells together Cell recognitions labeling the cell as distinct type Structure of the nucleus 0 Chromatin DNA that exists in thin threads 0 Nuclear envelop9 consists of two membrane and surrounds the nucleus Within nucleus is the nucleolus which is the site of synthesis for rRNA Nucleus functions as transmission and expression of genetic info 0 Nuclear pores allow selective movement of molecules between nucleus and the cytoplasm Contents of the cytosol o Gellike uid 0 Enzymes found that catalyze chemical reactions EX enzyme that breaks down glucose through glycolysis o lnclusions9 masses in the cytosol that stores energy in the form of triglycerides and glycogen o Secretory vesicles stores molecules to be secreted Endoplasmic Reticulum ER 0 Endoplasmic reticulum9 elaborate network of membranes enclosing an interior compartment called lumen Rough ER RER ribosomes presnet Smooth ER SER o Ribosomes9 function In protein synthesis 0 the ER important for synthesis of biomolecules proteins in RER lipids in SER triglycerides steroids and calcium ion storage SER in liver cells function to detoxify Golgi Apparatus o Consists of membranebound attened sacs called cisternae 0 One side faces ER cis face and other the plasma membrane trans face 0 Functions to process molecules synthesized in the ER and packages into vesicles for transport Mitochondria 0 Bound by 2 membranes 0 lntermembrane space9 area between two membranes o Mitochondrial matrix innermost compartment Houses electron transport chain Folded into tubules calles cristae o Mitochondira is the powerhouse of the cell because most ATP is formed here 0 Red blood cells lack mitochondria Lysosomes 0 Small spherical organelles surrounded y a single membrane 0 Contain enzymes that degrade debris recycle and eliminate waste product Peroxisomes o Spherical organelles that function in the oxidation and degradation of molecules such as amino acids fatty acids and toxic foreign matter 0 Produces hydrogen peroxide H202 o Abundant in the liver and kidney cells Ribosomes nonmembranous o Composed of rRNA and proteins and function in protein synthesis 0 Small subunit and large subunit 0 Proteins synthesized in RER will be packaged and sent to golgi Vaults nonmembranous 0 Used for cancer treatments 0 Barrel shaped comprising proteins and vault RNA vRNA 0 Function unknown but assist in intracellular transport and chemical signal for cell survival Centrioles nonmembranous o Cylindrical structures consisting of bundles of protein lament 0 Each cell has 2 0 Function in directing development of mitotic spindle during cell division Cytoskeleton 0 Flexible lattice of brous proteins or laments which gives the cell structure and support 0 Funtionfor structural support of the cell an cell movementcontraction 3 types form cytoskeleton micro laments smallest o EX actin which function in muscle contraction movement and cytokinesis Actin provide support for microvilli Actin is a globular protein calles G actin Intermediate laments larger diameter 0 Strongermore stable 0 EX keratin which is found in skinhair cells 0 EX myosin which is found in muscle cells Microtubules largest diameter 0 Undergo assemblydisassemny 0 Provide strength and from spindle bers during cell division 0 Components of cilia and agella Hairlike protrusions Flagella only found in human sperm CelltoCell Adhesions Cells are held together by membrane proteins called cell adhesion molecules 0 3 types tight junctions found in epithelium tissue digestive tract limiting molecule movement from lumen to blood specialized for molecular transport occludins o integral proteins that fuse adjacent cells together 0 form an impermeable barrier o transepithelial transport solutes cross epithelial layer to go from one side to the other desmosomes lamentous junction between cells 0 found in tissue subject to mechanical stress heart uterus skin 0 provide strength so cells do not tear apart when under stress gap junctions found in smooth muscle and in the heart composed of membrane proteins called connexons linking the cytosol of two adjacent cells 0 ions and molecules moving between cells act as a signal electrical and metabolic 0 allow communication to be direct allow passage of nutrients and some chemical messengers General Cell Functions metabolism 0 refers to all chemical reactions that occur in the body anabolism the synthesis of large molecules 0 requires energy catabolism break down of large molecules releases energy cellular transport 0 process of moving in and out of the cells in called membrane transport 0 nonpolar molecules can pass through the plasma membrane and diffuse across the phospholipid bilayer small polar molecules can also permeate large polar molecules cannot o polar molecules only with assistance from transmembrane proteinscarriers ions and water move through channels proteins and macromolecules are too large for carrier proteins or channels so they move through packaging into vesicles through vesicular transport lntercellular communication 0 Coordinate cell activity for homeostasis 0 Direct Gap junctions EX cAMP Ca 2 0 Indirect Chemical messengers that reach target cells by acting on a receptor on that cell EX insulin released by pancreatic B cells act on insulin receptors in most cells to facilitate glucose uptake EX ADH released into the blood by exocytosis reaches target cells in the kidney binding to receptors that stimulate the insertion of water channels into the kidney which increases water conservation Protein Synthesis in DNA are the codes for all proteins 0 the genetic code is universal and found among all animals 0 gene a portion of DNA holding the genetic code for particular proteins 0 genome the collection of genes in a given species 0 triplet a nucleotide sequence that codes for a speci c amino acid Steps of protein synthesis 0 Code for proteins Genetic code 0 DNA is transcribed in the nucleus to form a complimentary mRNA 0 mRNA moves from the nucleus to the cytoplasm 0 mRNA is translated by ribosomes to form the correct amino acid sequence of proteins in the cytoplasm The role of the genetic code 0 Only the template strand of DNA contains the actual code 0 A sequence of three bases is called a triplet A triplet codes for a speci c amino acid during transcription code passed on to mRNA whose base sequence will be complimentary to the template strand codon 3 base sequence of the triplet of the complimentary strand that will code for the same amino acid 0 codes for 20 amino acids triplet and codon 3base sequence 4 bases 4quot364 codons each codon codes for one amino acid EX CCC proline One amino acid can be coded by more than one codon EX CCC proline CCG9proline One initiation codon AUG9 methionine 3 termination codons nothing coded Figure 223 Thematic Ema Gene a Double strand of DNA 39 Triplet Triplet l9 Template strand V ufDN lei mRNlli W m Curl Ell l Calcium Carrion Transcription 0 Process RNA is synthesized using info contained in DNA happens in nucleus transcribed mRNA codons which are complementary to the code in DNA triplets b o 3 types of RNA can be transcribed from DNA each involved in protein synthesis mRNA messenger rRNA ribosomal tRNA transfer 0 Role of RNA polymerase enzyme First step is uncoiling the two strands RNA polymerase bind to a promoter sequence of DNA and uncoils it 0 Section of DNA with the gene is identi ed by the promoter sequencea speci c base sequence to which the enzyme RNA polymerase can bind Base uracil in RNA replaces thymine in DNA 0 PremRNA undergoes posttranscriptional processing in the nucleus before the nal mRNA product moves to the cytoplasm Posttranscriptional processing 0 Following transcription premRNA undergoes further processing Transcribed introns must be removes so that exons can be spliced togehet CAP is added to the 5 end and a poly A tall several nucleotides with the adenine base to the 3 end 0 Introns O O O Regions within a gene that contain excess bases that do not code May play a role in regulating transcription Must be removed before mRNA leaves the nucleus Exons The remaining coding segments Posttranscriptional processing is the addition of a chemical group 5 CAP necessary for initiating translation 3 poly A tail protects mRNA from degradation in the cytoplasm after processing is complete mRNA enters cytoplasm and translation can occur Translation occurs in cytoplasm and associated with ribosomes 0 Process polypeptides are synthesized using mRNA codons as a template for assembly of the correct amino acids tRNA will carry the appropriate amino acid to the ribosome based on interactions with the mRNA codon hydrogen bonding between complementary base pairs is responsible for the cloverleaf structure of tRNA tRNA binds to speci c amino acid on one end and on the other contains an anticodon that recognizes the complementary mRNA codon anticodon is the complimentary to the mRNA codon interaction between the mRNA and tRNA ensures the correct amino acid is added to the polypeptide chain 2 tRNA binding sites P site holds the tRNA with the last amino acid added to the polypeptide chain A site holds tRNA with the next amino acid to be added to the polypeptide chain initiation of translation initiation factors bind to the CAP region of an mRNA molecule and to the small ribosomal subunit triggering the binding of the small ribosomal subunit to the mRNA a tRNA with the anticodon complementary to the initiation codon of mRNA bind to the mRNA by the law of complementary base pairing the large ribosomal subunit binds such that the rst tRNA is located in the P site of the ribosome and the initiation factors are released following initiation tRNA molecules will occupy sites on the ribosome according to the complementary base pairing between the anticodon of the tRNA and the codon of the mRNA the tRNA carries the appropriate amino acid to be added to the polypeptide chain Enzymes in the ribosome catalyze the formation of a peptide bond The rst tRNA molecule is released from the P site of the ribosome and the ribosome moves down the mRNA molecule one codon putting the second tRNA in the P site A new tRNA occupies the A site bringing with it the next amino acid to be added to the chain This process continues until a termination codon is reached on the mRNA and the polypeptide is released and the ribosome and mRNA dissociates Destination of Proteins and Packaging of proteins 0 Determined by the leader sequence Leader sequence9 the rst functioning sequence of amino acids that is translated in a polypeptide chain Translation of the leader sequence requires ribosomes Free in the cytosol Attached to the RER If there is no leader sequence the protein remains in the cytosol To RER and SER eventually will go to the Golgi where it goes through posttranslational processing Posttranslational processing changes in the initial polypeptide chain in order to produce the nal protein product 0 Removal of the leader sequence 0 Cleavage of excess amino acids 0 Addition of a chemical group Lipids Carbohydrates glycosylation Important for protein folding stability and celltocell adhesion o Packaged rst in small transport vesicles by smooth ER 0 Fuse with the Golgi o Polypeptide travels to the trans face of the Golgi o Packaged into vesicles and targets them into the appropriate location 0 Synthesis of proteins on the ER When the leader sequence causes the ribosome to attach to the ER translation continues with the polypeptide forming in the lumen of the RER The polypeptide then moves to the lumen of the SER where it is packaged and transported into a vesicle The membrane transport vesicle fuses with the membrane of a cisterna on the cis face of the Golgi releasing the polypeptide into the lumen of the golgi The golgi packages the polypeptide into a vesicle and targets the vesicle to the appropriate location which could be a lysosome or the plasma membrane Regulation of protein synthesis and degradation 0 Regulation Some mRNA binds to proteins in the cytoplasm to render it inactive until an appropriate chemical signal is received Regulation of transcription at the level of RNA polymerase binding typically occurs at this step Induced turned on Repressed turned off Regulation of translation during initiation Active initiating factors turned on lnactive initiating factors turned off 0 Degradation Proteasomes contain proteases Proteases degrade proteins Ubiquitin Chemical tag to target proteins to move to the proteasome to be degraded Protein hat will cause rapid degradation in shortlived protein Cell Division most cells have a limited life span types of cell division 0 mitosis occurs in most cells replaces cells O meiosis occurs in reproductive cells begins with DNA replication Replication of DNA 0 0 Copying DNA replication Chromosome one complete DNA molecule plus associated proteins Humans have 23 pairs of chromosomes One paternal one maternal All 23 pairs make up the human genome Chromosomes are coiled around histones Chromatin chromosomes scattered in the nucleus During DNA replication each strand of DNA serves as a template for the synthesis of a new strand semiconservative Process starts with helicase an enzyme that causes a section of DNA to unwind and separate forming a replication fork The nucleotides align according to the law of complementary base pairing and the enzyme DNA polymerase catalyzes a reaction that adds the next nucleotide to the growing polynucleotide chain 0 The leading strand synthesized from the 5 to 3 parents strand and the lagging strand from the 3 to 5 parents strand 0 The lagging strand has okazzaki fragments that enzyme DNA ligase will link The Cell Cycle 0 O O lnterphase includes the periods between cell division and includes the four phases GO reenterexit cycle 61 growth S DNA replication 62 growth Mitosis and cytokinesis are the periods of actual cell division Mitosis includes 5 or 6 stages 1 Prophase chromatin pairs condense microtubules disassemble into tubulin components which form the mitotic spindle centriole pairs move to opposite poles of the cell mitotic spindle develops between centriole pairs 2 prometaphase nuclear envelope breaks down nucleolus is no longer visible centrioles are at opposite poles of the cell chromosomes become linked at centromeres to spindle bers 3 metaphase chromosomes are aligned in a plane at the middle of the cell 4 Anaphase chromatid pairs separate chromosomes move along the mitotic spindle towards opposite poles 5 telophase new nuclear envelopes develop chromosomes begin to decondense to chromatin mitotic spindle breaks down 6 Cytokinesis division of the cytoplasm divides by cleavage Chapter 3 Cell Metabolism Types of Metabolic Reactions 0 Metabolism the sum total of all chemical reactions that occur in cells 0 Energy metabolismreactions involved in energy storage and use 0 Chemical reactions involve reactants and products 39 Reacta nts products Forward reactants transformed into products Reverse products transformed into reactants Reactions bidirectional referring to overall net direction 0 Chemical reactions occurring in the body Catabolic9 breakdown of larger molecules into smaller Proteins into amino acids Glycogen broken down when digested Anabolic synthesis of larger molecules from smaller reactants Amino acids into proteins Glycogen from glucose 0 a series of reactions9 metabolic pathways A9B C9D Starting material initial substrate Yielding product end product Substances in the middle intermediates 3 types of metabolic reactions 0 1 Hydrolysis and condensation Hydrolysis water reacts with molecules breaking the bond that links molecules together AB H20 a A OH HB 0 Water molecules splits into a hydroxyl group and a hydrogen EX sucrose HZO glucose fructose Condensation reverse of hydrolysis involves joining together of two or more smaller molecules to form a larger one AOH HB a A B H20 0 Water molecule forms EX glucose fructose9sucrose H20 0 2 Phosphorylation and dephosphorylation phosphate group is addedremoved Phosphorylation addition of a phosphate P A P a AP EX ADP P a ATP H20 0 Formation of ATP from ADP Dephosphorylation9 removal of phosphate group AP a A P ATP H20 a ADP P also a hydrolysis reaction 0 3 Oxidationreduction central to energy metabolism ex cellular metabolism includes oxidation of glucose to water and carbon dioxide oxidative phosphorylation is primary nechanism for synthesis of ATP oxidation removes electrons oxygen is special in pulling electrons away reduction addition of electrons 2 H 2 e H2 A B 9 AB A is oxidized and B reduced Metabolic Reactions and Energy 0 Energy capacity to do work 0 Energy and the law of thermodynamics Kinetic energy associated with motion Includes thermal radiant electromagnetic electrical Potential energy stored energy that can eventually be converted to kinetic Includes chemical mechanical nuclear and gravitational First law of thermodynamic Energy in a closed system is constant 0 Energy can neither be created nor destroyed o The human body is an open system Second laW of thermodynamics Natural processes proceed in the direction that spreads out energy 0 Breaking large molecules to smaller 0 Movement of molecules from high to low concentration through diffusion Energy changes in reactions 0 All reactions involve an exchange of energy 0 Molecules posses energy 0 Reactants enter a reaction with a certain amount of energy and products come out with less Extra energy is released in another form EX combustion of gasoline reactants a products energy 0 Eproducts Ereactants o exergonic reaction energy releasing AE negative reactants posses more energy so proceeds spontaneously released energy may power an energyrequiring reaction catabolic reactions 0 endergonic reaction9 an energyrequiring reaction AE positive 39 products possess more energy so does not proceed spontaneously energy input is required anabolic reactions 0 AE expressed in calories orjoules calorie the amount of energy that must be put into 1 gram of water to raise its temperature by 1 degree Celsius 0 chemical energy energy stored in the chemical bond holding molecules together form of potential energy How the energy change of a reaction determines its direction 0 EX burning paper is exergonic proceeds in the forward direction 0 Truth of nature systems have a natural tendency to go from states of higher potential energy to lower 0 Free energy is the energy extracted from a molecule o Catabolic reactions occur spontaneously in cells and anabolic require energy Anabolic are able to occur in cells because they are coupled with catabolic reactions The energy released from catabolic is used to drive anabolic Chemical equilibrium 0 Equilibrium there is no net reaction direction Reactants are converted into products at the same rate products to reactants AE0 The law of mass action 0 The law of mass action an increase in the concentration of reactants relative to products tends to push a reaction forward and an increase in the concentration of products relative to reactants tends to push a reaction in reverse Equilibrium constant relationship between reactants and products at equilibrium K Equilibrium constant greater than 1 exergonic reaction Less than 1 endergonic Reactions allowed to proceed until equilibrium More reactants are then added and causes the production of more product Activation Energy 0 Transition state Reactant and products are not transformed suddenly Instead go under a highenergy intermeadiate form called a transition state Continuous and gradual Activation energy barrier hump that arises because the potential energy of the transition state is greater than that of either the reactants or products Activation energy 39 barrier Reactants Energy Products Extent of reaction zml l O For reactants to become products or vice versa molecules must have suf cient potential energy to surmount activation barrier To do so require extra energy called activation energy difference between the energy of the transition state and energy of reactant or products Extra energy comes from molecules colliding with each other 0 More quickly two molecules are about to collide the more potential energy they gain If less than the activation energy they will not enter transition state The activation energy barrier limits how fast a reaction can go Reaction Rates rate how fast reactants are consumed and products are generated rate is important in physiology because body function requires that reactions proceed at a rate that matches the body s needs hypothermia decline in the body temperature causes metabolic reactions to slow Factors Affecting the Rates of Chemical Reactions 0 1 reactant and product concentrations reaction rate refers to net rate difference between a forward reaction and reverse according to the law of mass action any increase in the concentration of reactants increases the forward rate and increase in concentration for products increases reverse rate increase in concentration of reactants increases net forward but increase in product decreases net forward also as the concentration of molecules increases collisions occurring also increase at that time o 2 temperature increase in temperature increase rate decrease temperature decrease rate hypothermia and hyperthermia o 3 the height of activation energy barrier decreased height increased rate increased height decreased rate The role of Enzymes in Chemical Reaction enzymes biomolecules proteins specialized to act as catalysts increase reaction rates 0 function by decreasing the activation energy for a speci c chemical reaction 0 Enzymes identi ed by suf x ase EX RNA polymerase DNA uncoilingsynthesis of RNA DNA polymerase DNA uncoilingsynthesis of DNA protein kinase phosphorylation phosphoprotein phosphatase dephosphorylation Mechanism of Enzyme Action 0 Enzymes rst bind to a reactant molecule a substrate a binding step When substrate binds it is through a weak interaction Hydrogen bond ionic not covalent Ligand is any molecule that binds to a protein 0 If stays bound it will be converted to a product in the catalytic step Can also happen in reverse by binding to product 0 Enzymes are neither consumed nor altered in the reaction Enzyme PropertiesSubstrate Speci city o Enzymes are speci c for one set of substrategroup of substrates Recognize and bind EX pepsin enzyme secreted by cells in the stomach and breaks proteins in food into smaller polypeptides Pepsin can also act on any other protein as long as it has certain amino acids 0 Basis of substrate speci city relates to complementary shape of enzymesubstrate 0 Enzyme has active site for substrate 2 models lock and key model 0 does not explain reversibility of enzyme reactions 0 substrate matches active site Figure 3133 The we manualth spec39lm lty In tnernecnanlsm warrenzyrne action 5m Enzyme free tc bind 1with substrate mclecule v quot Substrate binds tc enzyme mulecule substrate may leave active site 39 unchanged hl leaves quot enzyme Enzymesubstrate v 39 cum plea quotall Substrate may beccnverted quot 39 tc preduct by enzyme mil3 Product damn O induced t model 0 explains reversible reactions 0 active site approximately ts substrate and product like foot ts a sock 0 when substrate begins binding conformational change occurs in enzyme to t better and reaction takes place Figure 37 Induced m quotmm9mm activity Substrate produat Substrate Product Va ewEW mm Enzyme En zyme E n name Enzyme m39zmm III 0 Cofactors and Coenzymes o Cofactors ions or molecules nonprotein required by the enzyme for it to be active by binding tightly to certain amino acids holding enzyme in normal conformation EX iron copper zinc o Vitamins9 organic molecules of which trace amount is required for proper functioning Contained by other enzymes Some vitamin derived factors function as coenzymes9 molecules that do not themselves have catalytic activity but participate directly in the reactions catalyzed by enzymes Transfer chemical groups during chemical reactions 3 coenzymes important in energy metabolism 0 FAD from vitamin BlZ ribo avin Participate as hydrogen carrier Reduced to FADH2 0 NAD from vitamin BB niacin Participate as hydrogen carrier Reduced to NADH o Coenzyme A CoA from vitamin BS pantothenate Role in glucose oxidation Factors Affecting the Rates of EnzymeCatalyzed Reactions Enzymes cannot affect the direction of a reaction or energy releasedrequired only the rate at which reaction occurs Enzyme catalytic rate how many molecules are generatedunit time Some generate thousandssecond and some 1min Rate of enzyme reaction affected by 1 catalytic rate 0 catalytic rate how many product molecules is generated per unit time re ects how fast an enzyme can carry out the catalytic step rate of enzymatic reaction increases as catalytic rate increases 2 substrate concentration increase as substrate concentration increases law of mass action enzyme concentration low more time passes before next substrate binds at high concentration curve levels off indicating any increase will fail to raise rate 0 enzyme 100 saturated 3 enzyme concentration the rate of enzyme reaction increases as enzyme concentration increases law of mass action 4 af nity of enzyme to substrate af nity how tightly substrate binds to active site high af nity higher rates 0 high af nity enzyme able to generate more product 0 can reach 100 saturation where rate will no longer increase 0 temperature and pH also affect rate of enzymecatalyzed reactions enzyme activity declines if pH or temperature become too lowhigh Regulation of Enzyme Activity 0 1 allosteric regulation each enzyme has an active site and a regulatory site for modulators induce a change in enzyme conformation that alters the shape of the active site can increasedecrease activity af nity o increase activation o decrease inhibitor occurs in weak interaction so is reversible o 2 covalent regulation covalent regulation changes in an enzyme s activity occur as a result of the covalent bonding of a speci c chemical group to a site on the enzyme enzymes exist in activeinactive state changing state requires formation of a covalent bond between enzyme and chemical group breaking bond requires other enzyme most common chemical group phosphate o EX additionremoval or phosphate Phosphorylation catalyzed by protein kinase Dephosphorylation catalyzed by phosphatase 0 3 feedback inhibition enzyme that catalyzes the slowest reaction rate limiting enzyme feedback inhibition an intermediate product of metabolic pathway allosterically inhibits enzyme that catalyzed an earlier reaction regulates enzyme activities so as to hold rates of metabolic pathways steady allosteric inhibition in feedback inhibition is end protrude of the metabolic pathwayendproduct inhibition enzyme allosterically inhibited is ratelimiting enzyme could be branched pathways converted to eitheror o 4 feedforward activation rare feedforward activation involved the activation of an enzyme by an intermediate appearing upstream in a metabolic pathway helps keep reaction rates steady under normal conditions ATP The Medium of Energy Exchange energy released by exergonic reactions used to synthesize adenosine triphosphate ATP serves as temporary energy storage temporary because eventually is broken down to ADP and Pi 0 synthesized from ADP and a phosphate ADP Pi energy a ATP H20 A condensation reactionphosphorylation reaction ATP synthesis occurs through 0 1 substratelevel phosphorylation phosphate group is transferred from a metabolic intermediate to ADP to form ATP EX creatine phosphate donates phosphate to ADP o 2 oxidative phosphorylation ADP binds with a free inorganic phosphate Pi to form ATP 39 requires the electron transport system 0 when cells need energy for work obtain it by hydrolyzing ATP Glucose Oxidation The Central Reaction of Energy Metabolism glucose can be used to produce and store energy to maintain all body processes we derive most of our energy from reaction of oxygen with glucose 0 when oxygen reacts with glucose energy is released 0 C6H1206 6 02 6 C02 6 H20 energy AE 686 kcalmole net energy negative because releases more energy than used for ATP synthesis proceed forward because AE is negative Coupling Glucose Oxidation to ATP Synthesis 0 When cells use glucose oxidation to make ATP energy released in the reaction is used to drive energyrequiring process of ATP synthesis 0 Breakdown of ATP releases energy used to perform cellular work 0 Body heat is heat generated as a byproduct of metabolic reactions Stages of Glucose Oxidation Glycolysis the Krebs Cycle and Oxidative Phosphorylation Oxidation of glucose occurs in 3 stages 0 1 Glycolysis 39 takes place in cytosol quotsplitting of sugarquot through 10 enzymecatalyzed reactions each glucose molecule 6 carbons broken down in to two pyruvate 3 carbon in the process 2 netATP produced 4 total but 2 consumed 2 NAD molecules reduce to NADH No 02 consumed no C02 produced First step in cycle and if oxygen in ETC not available later pyruvate converted to lactic acid REACTION glucose 2 NAD 2 ADP 2 Pi 9 2 pyruvate 2 NADH 2 H 2 ATP 0 15 Linking step from GLYCOLYSIS to KREBS CYCLE unidirectional 39 pyruvate enters mitochondrial matrix where pyruvate is converted to acetyl CoA Acetyl CoA initial substrate to enter Krebs Cycle 1 NADH molecule produced per pyruvate 2 total 1 C02 per pyruvate produced 2 total REACTION pyruvate CoA NAD9acetyl CoA C02 NADH H o 2 Krebs cycle AKA citric acid cycle TCA cycle occurs in mitochondrial matrix and is cyclical acetyl CoA initial substrate by the end of each cycle 1 ATP produced 2 C02 molecules produced as waste 3 NADH 3Hproduced 1 FADH2 produced As glucose generate 2 acetyl CoA so cycle turns twice Oxygen was not consumed REACTION acetyl CoA 3 NAD FAD ADP Pi 3 H2092 C02 3 NADH 3 H FADH2 ATP CoA BY KREBS CYCLE NET GAIN OF 4 ATP 0 3 Oxidative phosphorylation requires oxygen most ATP formed occurs in inner mitochondrial membrane involves 2 processes simultaneously 1 Electron Transport Chain transport in the inner mitochondrial membrane of H atomselectron 2 Chemiosmotic Coupling harnessing of energy to make ATP through ATP synthase reduced coenzymes NADH and FADH2 serve as energy source for making ATP by releasing electrons in ETC Electron 7739an5p0rt Chain lnner mitochondrial membrane Chain of molecules that undergo oxidation reduction reactions and energy released used to synthesize ATP through oxidative phosphorylation and ATP synthase Cytochromes and ironsulfur proteins attached to large complexes that hold electrons 0 As they move through complexes energy is released which is used to transport hydrogen ions across the inner mitochondrial membrane creating the concentration gradient Electrons carried to ETC by coenzymes NADH and FADH2 o NADH to avin mononucleotide FMN 1St electron acceptor and becomes oxidized to NAD and FMN reduced 3 ATP synthesized for every pair of electrons released by NADH NADH HNAD2H2e o FADH2 bound to another enzyme so donates electrons to coenzyme Q where FADH oxidized to FAD and coenzyme Q reduced 1 or2ATP produced by each FADH2 net reaction NADH H 12 02 a NAD H20 energy electrons move to the nal electron acceptor 02 oxygen 0 net reaction FADH2 12 02 a FAD H20 energy released electrons and protons come together again in the mitochondrial matrix to form water as an endproduct Chemiosmotic Coupling Energy used to make ATP Chemiosmotic coupling9 couples electron transport to ATP synthase by using energy released in the electron transport chain to transport hydrogen ions across the inner mitochondrial membrane AGAINST their concentration gradient which is used to make ATP ATP synthase catalyzes the formation of ATP resides in the inner mitochondrial membrane 10 molecules of NADH and 2 molecules of FADH2 are generated for every glucose molecule oxidized34 ATP made during oxidative phosphorylation net reaction 10NADH 10 H 2 FADH2 34ADP 34 Pi 602 10 NAD 2 FAD 12 H20 34 ATP Summary of glucose oxidation 0 For every glucose molecule 6 02 consumed 6 C02 and H20 produced overall PER GLUCOSE 38 ATP Net reaction glucose 6 02 38 ADP 38 Pi 6C02 6H20 38ATP Glucose Catabolism in the Absence of Oxygen Low oxygen availability electron transport chain backs up Krebs cycle stops glycolysis continues only if NADH is oxidized Oxygen is the last acceptor so and supplies tissues on a conUnualbasE 0 Consumption depends on tissues metabolic demand In the event of low oxygen availability enzyme lactate dehydrogenase LDH converts pyruvate to lactate and allows electrons to be unloaded in another reaction yielding free NAD ensuring cells have a steady supply of NAD which allows glycolysis to continue in lack of oxygen Conversion of pyruvate to lactate o Allows muscles to operate in low oxygen 0 ATP production is inef cient 0 When oxygen levels return lactate converted back to pyruvate gluconeogenesis and oxidative phosphorylation returns 0 Build up of lactate is disruptive and removed through liver where converted back 0 Cori cycle most of the lactate is produced in muscle cells transported by blood to liver converted to glucose and transported by blood to muscle cells Energy Storage and Use Metabolism of Carbohydrates Fats and Protein the body is able to draw on fats and proteins as alternatives when glucose is scarce when supply of glucose is plenty glucose storage called glycogen oneway reactions are irreversible and require a lot of energy to go in reverse 0 can be a bypass reaction different route that skips enzymes that catalyze forward reaction 0 when in forward enzymes catalyzing bypass are turned off 0 when in bypass enzymes catalyzing forward are turned off Glycogen Metabolism carbohydrate O Glycogen a branchedchain molecule found in animal cells similar to starch in plants Stored in the liver and kidney Have enzyme glucose6phosphatase which converts to glucose Only glucose can leave the cell not quot 0 When glucose is abundant stored as glycogen through9glycogenesis Breakdown of glycogen into individual glucose glycogenolysis Gluconeogenesis Formation of New Glucose o Nervous system requires uninterrupted supply of glucose or loss of consciousnessdeath Glucose can be synthesized from noncarbohydrate precursors via9 gluconeogenesis Gluconeogenesis is carried out by the liver because the liver has enzymes to run glycolysis in reverse Glucose made from o Glycerol Produced by the breakdown of triglycerides Triglycerides lipases a glycerol 3 fatty acids 0 Once glycerol broken down 0 20 ATP Fatty acids cannot be converted into glucose 0 Lactate 0 Amino acids Produced by the breakdown of proteins Certain amino acids can be converted to glucose after rst converted to pyruvate ln gluconeogenesis 0 glycerol is rst converted to glycerol phosphate 0 lactate is rst converted to pyruvate 0 products then proceed glycolysis in reverse so more glucose is generated Acetyl CoA cannot be converted into glucose Fat Metabolism o Fats synthesized to store energy and can be used for energy Adipose tissue stores energy triglycerides stored here Lipids have greater energy per weight than ca rbsproteins 0 Most energy is stored in triglycerides 3 fatty acids glycerol 0 Lipolysis rst stage of fat breakdown separation of fatty acids from glycerol molecule Fatty acids catabolized to acetyl CoA by process9 beta oxidation which occurs in mitochondrial matrix Fatty acids a betaoxidation 2 C at a time 0 Each 2 C a acetyl CoA NADH FADH o Acetyl CoA a Krebs cycle 0 NADH FADH a electron transport chain 0 17 ATP from each 2 C If triglycerides are broken down at a quick rate ketones are generated as byproduct This is good because the nervous system utilizes ketones as an alternative to partial glucose Ketones are acids and produce a state of ketoacidosis so they can alter acidbase balance 0 Lipogenesis synthesize fats from other nutrients Protein Metabolism o Proteolysisabreakdown of proteins to amino acids 0 Amino acids are then deaminated Amino group NH2 is removed Producing keto acid ammonia o Keto acid is then converted to pyruvate or acetyl CoA and goes to Krebs cycle 0 Other amino acids cannot be synthesized and must be obtained in the diet Known as essential amino acids Essential nutrient9any biomolecule necessary for proper body function that cannot be synthesized in cell Isoleucine lucine lysine methionine phenylalanine threonine tryptophan valine CHAPTER 4 CELL MEMBRANE TRANSPORT l FACTORS AFFECTING THE DIRECTION OF TRANSPORT To get started right away just tap any placeholder text such as this and start typing A Energy Difference Energy difference in the molecule on the two sides of the membrane determines the direction of spontaneous transport passive transport and need for energy to move the molecule against the energy gradient active transport B Passive Transport vs Active Transport vi vii Viii Spontaneouspassive movement occurs from areas of high energy to areas of low energy When they need to move in opposite direction it requires an input of energy Energy of solute depends on solute concentration and charge if solute is ion energy increases as solute concentration increases Solutes move passively from an area where they are in greater concentration to an area where they are in lesser concentration To move from an area of low concentration to high requires input of energy Active transport transport of molecules across a membrane if it requires energy Passive transportdoes not require energy Simple diffusionthe movement of a molecule into or out of the cell by its own thermal motion one form of passive transport Active transport is always mediated by transport proteins referred to as pumps Glucose example 1 Concentration is 1 mM in intracellular uid but it is nearly 6mM in extracellular uid 2 If glucose is allowed to move spontaneousy across membrane of typical cell it Will move from area of higher concentration to area of lower concentration move into cell 3 Transport of glucose in opposite direction from lower to higher is active because it requires energy and does not occur spontaneous y C Driving Forces Acting on Molecules Driving forceany difference in energy existing across a membrane that tends to push molecules in one direction or another Direction is always higher to lower Driving forces can arise as a result of concentration differences or other factors that affect molecular energies Molecules are generally in uenced by three types of driving forces chemical electrical and electrochemical 1 Chemical Driving Forces a Concentration gradient when a substance is present in different concentrations on either side of a membrane this exists across a membrane When molecules are moving from higher to lower concentration we can say that they are moving down a concentration gradient movement in the opposite direction is up a concentration gradient Concentration gradient is a force that quotpushesquot molecules in a particular direction Chemical driving force the direction of which is always down the concentration gradient The rate at which a substance is transported varies with the size of the concentration gradient and generally increases as the size of the gradient increases When more than one substance is present as is the case with real cells more than one concentration eXists Any chemical driving force that might be acting on a given substance depends only on the concentration gradient of that particular substance Chemical driving force is fundamentally different does not act the same as the force of gra vity does when molecules move across a membrane down a concentration gradient they do so simply because more molecules are present on one side of the membrane than the other Individual molecules are not pushed down the gradient but are equally likely to move in either direction j PAGE 96 for Photos to help Visualize 2 Electrical Driving Forces a Electrical driving forces arise due to membrane potential a difference in electrical potential or voltage that exists across the membrane of most cells b Membrane potential re ects an unequa distribution of positively charged ions and negatively charged ions across the plasma membrane c The membrane potential the uids in the body contain a Wide variety of solutes including many ions also called electrolytes substance possessing a chemical charge Cations have positive electrical charge Anions have negative electrical charge lons are also present in salt solutions such as sea water Something is considered electrically neutral beca use the positive and negative charges cancel each other out giving a total net charge of 0 Human s bodies are electrically neutral however a person can pick up or emit charges lntracellularextracellular uid cations and anions are present in unequal numbers these uids are not electrically neutral lntracellular uid contains a slight excess of anions over cations giving it a net negative charge Extracellular uids contain a slight excess of cations over anions giving it a net positive charge A separation of charge is said to exist across the membrane because positive and negative charges are distributed unequaly between the inside and outside of cell When charges are separated a potential energy voltage exists The excess negative and positive charges of intracellular and extracellular uid tend to be clustered close to the membrane because the excess negative charges on one side of the membrane are attracted to the excess positive charges on the other side A cell 5 membrane potential re ects the separation of charge and is given in units of electrical potential in milivots m V which are 11000 of a volt The magnitude of the membrane potential depends on the degree of charge separation the greater the difference in charge between the two sides of a membrane the larger the membrane potential The sign of the membrane potential is taken to be the sign of the net charge inside the cell relative to outside 0 How the Membrane Potential Creates an Electrical Driving Force that Acts on Ions An electrical potential is a form of potential energy that is an electrical force acting on the charged particles and has potential to cause those particles to move Current in biological systems is caused by ion movement the membrane potential creates an electrical driving force for the movement of ions To determine the direction of electrical driving force we need to know the valence or charge of the ion the sign of the membrane potential usualy negative Opposites attract likes repel Cations are attracted by the negative charge inside the cell and have an in ward directed electrical driving force Anions are repelled by the negative membrane potential and have an outwarddirected electrical driving force Uncharged molecules glucose are not affected by the membrane potential and therefore have an electrical driving force of zero The magnitude of the electrical driving force on an anion depends on the size of the membrane potential and the quantity of charge carried by the ion and it increases as either of these factors gets larger A larger negative membrane potential means a greater number of negative charges inside and positive charges outside which increases the attractive and repulsive forces acting on an ion If an ion carries more charge the attractive and repulsive forces are also increased which makes the electrical driving force stronger 3 Electrochemical Driving Forces a When ions are transported across membranes two driving forces are in uential 1chemical force re ecting the ions tendency to move down their concentration gradients from higher to lower and 2 electrical force re ecting the ion 5 tendency to be pushed in one direction or the other by the membrane potential b Electrochemical driving force the total force acting on the ions is a combination of these chemical and electrical driving forces also known as uncharged molecules which are not in uenced by electrical driving forces in this case the electrochemical driving force is synonymous with the chemical driving force c The direction of the electrochemical driving force acting on an ion depends on the net direction of the electrical and chemical driving forces 0 If both forces go in the same direction then the electrochemical driving force also acts in the same direction e If the electrical and chemical forces go in opposite directions then the electrochemical force acts in the direction of the larger force f To determine whether the electrical or chemical force is larger we need to know an ion 5 equilibrium potential hypothetical value for the membrane potential at which the electrical driving force is equal and opposite to the chemical driving force producing an electrochemical driving force of zero g If membrane potential equals the equilibrium potential for an ion that ion will not move spontaneously in either direction because the total driving force acting on it is zero Ion will be at equilibrium h Chemical reaction is at equilibrium when its net direction is neither forward nor backward i The magnitude and sign of the ion 5 equilibrium potential depend on the size and direction of the ion 5 concentration gradient and on the ion 5 valence Larger concentration gradients mean larger equilibrium potentials because a greater electrical force is required to equal or quotbalancequot a larger chemical force j The sign of the equilibrium potential is such that the electrical force goes in the direction opposite to the chemical force k Na sodium are found in higher concentration outside a cell the chemical force is directed in ward because it charged positivey a positive membrane potential will exert an outward electrical force that balances the in ward chemical force Na equilibrium potential must be positive Outwardy directed electrical force is required to balance the chemical force m Determining the Direction of the Electrochemical Driving Force STEPS FOR THIS PROCEDURE CAN BE FOUND ON PAGE 98 n Signi cance of Electrochemical Driving Force the electrochemical force is the total driving force acting of transported ions it determines the direction in which the ions move if they are allowed to cross the membrane spontaneousy when ions are transported passively they always move in the direction of the electrochemical driving force they move down their electrochemical gradient when transported actively they move in the direction opposite to the electrochemical force or up their electrochemical gradient Molecules cross the membrane by simple diffusion under two conditions 1 when their concentration is the same on both sides 2 when the concentration on the left side is twice that on the right side 2 RATE OF TRANSPORT A The rate of a metabolic transport is important because reactions must proceed at a rate fast enough to meet the body s metabolic demands molecules must be transported across membranes at suf cient rates The rate at which a substance is transported across a membrane refers to the number of molecules that cross the membrane in a given length of time which is called the ux Flux is usually expressed in units of moles per second or some equivalent Molecules cross a membrane by simple diffusion under two set conditions 1 when their concentration is the same on both sides 2 when the concentration on the left is twice than on the right iv Transport rates are in uenced by many variables some of which are speci c to certain transport mechanisms V PAGES 101 102 HAS FIGURES FOR EXAMPLES OF RULES 3 PASSIVE TRANSPORT A Molecules move across the membrane down their chemical or electrochemical gradients no energy is required types of passive transports simple diffusion facilitated diffusion diffusion though ion channels B Simple Diffusion Passive Transport Through the Lipid Bilayer i Least complicated of all transport mechanisms ii The Basis for Simple Diffusion 1 Simple diffusion passive transport of molecules through a biological membrane s lipid bia yer but in fact the mechanism of simple diffusion is not strictly biological ex Perfume bottle 2 Diffusionmovement of molecules from one location to another simply as a result of their own thermal motion iii Factors Affecting Rates of Simple Diffusion 1 When a substance is transported passivey across a membrane by simple diffusion the rate at which it is transported depends on three factors 1 Magnitude of driving force 2 the membrane of the surface area 3 the permeability of the membrane a measure of the ease with which molecules are able to move through it 2 Magnitude of the Driving Force a When a driving force acts on molecules crossing a membrane it in uences not only the direction but also the rates at which they are transported b The net ux increases as the magnitude of the driving force increases not always though c In simple diffusion the rate of transport is directly related to the size of the driving force 3 Membrane Surface Area a The rate at which molecules are transported across a membrane varies in direct proportion to the membrane s surface are b Various tissues are specialized for transport the pulmonary epithelium the intestinal epithelium walls of capillaries all have larger membrane surface areas which enhance ability of these tissues to transport large quantities of material quickly 4 Membrane Permeability a The permeability of a membrane to a particular substance depends on both the nature of the transported substance and the properties of the membrane other than surface area that in uence the ease with which molecules are able to penetrate it b For passive transport a higher permeability translates into a higher rate of transport other things being equal c Factors In uencing Permeability of Cell Membranes Lipid solubility of the diffusing substance hydrophobic substances of are the most lipid soluble whereas h ydrophiic substances are least lipid soluble the more lipid soluble a substance is the greater a membrane s permeability to that substance The size and shape of diffusing molecules Molecules vary considerably in their sizes physical dimensions and molecular weights and shapes larger molecules and those with more irregular shapes move through bia yer more slowly making permeability membrane lower Temperature molecules move faster at higher temperatures which increases permeability however not common in human body because body temperature is relati vel y constant Membrane Thickness tissue thickness varies considerably tissues specialized for transport have rea ti vely thin walls this thinness increases the permeability and enhances rate of transport Lipid solubility has the strongest in uence on permeability Substances that can be transported by simple diffusion fatty acids steroid hormones thyroid hormones oxygen carbon dioxide and fatsoluble vitamins A D E K C Facilitated Diffusion Passive Transport Utilizing Membrane Proteins ii Carriers in Facilitated Diffusion carrier is a transmembrane protein that binds molecules on one side of a membrane and transports them to one side by means of a conformational change they possess one or more binding sites that are usually speci c for molecules of certain substances or classes of substances examples are monosaccharides and amino acids to be transported a molecule must rst enter a binding site once the molecule is in the binding site the carrier undergoes a conformational change that exposes the binding site to the uid on the other side of the membrane molecule is free to dissociate from the carrier and be released into the uid conformational changes may be triggered by solute binding or may occur When binding sites are empty if a molecule does not bind to a site the carrier can then revert to its original conformation With the binding site empty the net ux of facilitated diffusion depends on the frequency of solute binding to the carrier molecule on the two sides of the membrane so net transport occurs from the side With a greater frequency of binding two factors affect the binding site 1 the affinity of the binding site on the carrier 2 the concentration gradient or electrochemical gradient if ions are being transported of the solute across the membrane an y difference in the binding of solute to carrier on either side of the membrane depends on the concentration gradient soute is most likely to bind the carrier When there is more solute present if a concentration gradient is present more solute binds to carriers When the binding sites are facing the side With the greater solute concentration if solute is present at the same concentration on both sides of the membrane then solute Will bind equaly When the carrier faces either side of the membrane and the net ux is zero if a concentration gradient exists the direction of the net ux is down the gradient iii Factors Affecting the Rate of Facilitated Diffusion 3 factors 1 transport rates of the individual carriers 2 the number of carriers in the membrane 3 the magnitude of the concentration or electrochemical gradient of the transported substance an increase in any of these factors translates into an increased rate of facilitate diffusion individual carriers transport molecules at different rates depending on their type PAGE 105 HAS FIGURE TO ILLUSTRATE When the concentration of molecules on one side of a membrane is high the likelihood that at any given time the binding sites are occupied by molecules is also high if concentration is high binding sites are occupied 100 of time cells can regulate the rate of facilitated diffusion by modifying the number of carriers that are present in the membrane an increase in the number of carriers Will increase the likelihood that solute will bind to carrier and be transported across the membrane D Diffusion Through Channels A channel is a transmembrane protein that transports molecules via a passageway or pore that extends from one side of the membrane to the other channels are usually speci c for certain substances or classes of substances 1Diffusion of Water Through Aquaporins most water diffuses across cell membranes through aquaporins highly selective pores that permit water but no solutesto move across the membrane by diffusion 13 have been identi ed Water can also cross cell membranes through ion channels 2 Diffusion Through Ion Channels the mechanism of transport through an ion channel depends on the type of channel When a channel has numerous binding sites ions move through the pore by quotjumpingquot from one site to the next an empty channel 5 binding sites are accessible from both sides of the membrane at the same time in contrast for a carrier the sites are accessible from only one or the other at any given time 3 Factors affecting the Rate of Transport Through Ion Channels the rate of ion movements through channels depends on the transport rate of individual channels and the number of channels in the membrane the rate of individual channels varies depending on the type of channel channels that function primarily as pores ion movement follows the same basic principles as simple diffusion except that ions move down electrochemical gradient not just chemical gradient for ion channels with binding sites transport is generally slower and the channels can be saturated similar to what occurs with facilitated diffusion most ion channels can eXist in two conformations l a closed state 2 and open state in closed state ions cannot move through the channel in open ions diffuse through the channel down their electrochemical gradients the rate of transport depends on the number of quotopenquot ion channels 4 ACTIVE TRANSPORT A 11 The importance of active transport to the life of a cell is that some cells expend large amounts of energy as much as 40 of ATP Many things depend on active transport whether directly or indirectly generation of electrical signals in neurons and other excitable cells regulation of muscle contraction absorption of nutrients and water by the digestive system and body uid regulation by the kidneys Transport of a substance down an electrochemical gradient requires no energy transport of a substance up an electrochemical gradient requires an input of a substance up an electrochemical gradient requires energy because molecules are moving against the electrochemical force pushing them 2 rules for transport 1 if the direction of the net ux is down an electrochemical gradient the transport is passive 2 if the direction of the net ux is up electrochemical gradient the transport is active J K 12 Primary and Secondary active transport differ in the nature of the energy source Primary active transport uses ATP or some other chemical energy source directly to transport substances proteins involved are called pumps Secondary active transport is powered by a concentration gradient or an electrochemical gradient that was previously created by primary active transport Active transporters can harness energy to drive the transport of molecules in a preferred direction across a membrane Primary Active Transport The membrane proteins that perform primary active transport function both as transport proteins and enzymes Sodium and Potassium pump is present in every cell and is crucial to several important processes electrical signaling in neurons and absorption of glucose by intestinal epithelial cells For each cycle of the pump 3 Na ions are transported out of the cell and two K ions are transported into the cell transport is active in each case because both types of ions move up their electrochemical gradients Secondary Active Transport A transport protein couples the flow of one substance to that of another one substance moves passively down its electrochemical gradient in the process releasing energy that is then used to drive the movement of the other substance up its electrochemical gradient Cotransport the transport of two substances in the same direction Countertransport the transport of two substances in opposite direction PAGE 109 SHOWS FIGURE TO DESCRIBE PROCESSES WITH EXAMPLES Factors Affecting Rates of Active Transport Two factors of sole determinants of the rate at which molecules are actively transported across any membrane 1 the rate of transport by individual active transporters 2 the number of active transporters that are present in the membrane As either variable increases so does the rate of transport increases Transport rate can be in uenced by concentration of transported substance size of the electrochemical driving force for that substance L Coexistence of Active and Passive Transport Mechanisms in Cells PAGE 110 HAS CHARACTERISTICS OF TRANSPORT PROCESSES 5 OSMOSIS PASSIVE TRANSPORT OF WATER ACROSS MEMBRANE 6 A Water transport is important water transport is always passive unaffected by membrane potentials and is always driven by its own concentration gradient B Osmosis the flow of water across a membrane down its concentration The direction of passive water ow into or out of the cell depends on the direction of the water concentration gradient across the plasma membrane Osmolarity Known as the total solute particle concentration of a solution lsoosmotic two solutions having the same osmolarity Hyperosmotic a solution whose osmolarity is higher than another Hyposmoticsolution whose osmolarity is lower E Osmotic Pressure vi vii A solution39s total solute concentration As total solute concentration increases so does osmotic pressure Tonicity a function of the concentration of nonpermeating solutes outside a cell relative to the concentration inside the cell and it determines the behavior of a cell placed in the solution lsotonic when it does not alter cell volume when a cell comes into contact with an isotonic solution it neither shrinks nor swells Hypertonicshrink Hypotonicswell FIGURE 419 ON PAGE 113 EXPLAINS TONICITY VS OSMOLARITY TRANSPORT OF MATERIAL WITHIN MEMBRANEBOUND COMPARTMENTS 13 A Macromolecules are too large to cross the plasma membrane even with the assistance of proteins thus they are transported across with assistance of vesicles Endocytosismolecules in the extracellular uid enter the cell through the formation of vesicles calls endosomes B Transport of Molecules into Cells By Endocytosis Phagocytosiscell uses amoeboidlike movements of plasma membrane to extend the membrane around particulate matter in extracellular uid Pinocytosisplasma membrane develops an indentation and its outer edges pinch together to form an endosome in cytoplasm Receptormediated endocytosis speci c proteins in the plasma function as receptors that recognize and bind speci c particles in the extracellular uid Clathrin area of plasma membrane that forms the vesicle that is coated with proteins C Transport of Molecules Out of Cells by Exocytosis Three functions 1 Add components to the plasma membrane 2 To recycle receptors removed from the plasma membrane by endocytosis 3 To secrete speci c substrates out of the cell and into the extracellular uid 7 EPITHELIAL TRANSPORT MOVEMENT ACROSS TWO MEMBRANES A Epithelial Structure Apical membrane membrane on the side that faces lumen of body cavity Basement membrane anchors the basolateral membrane and provides physical support for the epithelial layer B Epithelial Solute Transport C Epithelial Water Transport Epithelia absorb or secrete water by rst using the active transport of solutes to create a difference in osmotic pressure Because water ow occurs in response to transport of solutes water transport is said to be secondary to solute transport D Transcytosis 14 15 Macromolecules cross epithelial cells which involves both exocytosis and endocytosis A large molecule is take into the cell by endocytosis but the endocytotic vesicle does not fuse with a lysosome Vesicle travels to the opposite side of the cell and fuse with the plasma membrane to release its content by exocytosis Ch 5 Notes Chemical Messengers 51 Mechanisms of Intercellular Communication 0 Almost all body functions require communication between cells 0 Some cells communicate through gap juctions that are made by connexins plasma membrane protein that forms the connexonsL o The connexons form the channels that allow ions and molecules to move from cells through cells though their inner gaps 0 These gap junctions make the cells behave as one 0 Communication through chemical messengers occurs when one cell releases a chemical secretion and another cell target cell responds to it o The target cells have a receptor for the speci c chemical that binds it to that speci c cell 0 The binding of messengers to receptors produces a response that is followed by a mechanism called The strength of the target cell response increases as the number of bound receptors increases 52 Chemical Messengers There are 3 main categories of messengers 1 Paracrines a chemicals that communicate with neighboring cells i The cells need to be close enough so that once the chemical is released it can easily diffuse into the cell ii These chemicals include growth factors clotting factors and cytokines peptides that have the function to coordinate the body s defense against infection iii Examples of other paracrines 1 Histamine responsible for allergic reactions and in ammation a Produces allergic reactions like watery eyes and runny nose b In in ammation histamine increases the blood ow of affected tissues causing redness and causes uid to leak out of blood vessels into the tissue which causes swelling b a sub class of paracrines that act on the same cell that secreated them i The secretory cell is also the target cell and the secretory cell regulates its own secretion 2 Neurotransmitters a chemicals released into the interstitial uid by nephrons i Released from the axon terminal which is very close to the target cell ii The cell that releases the neurotransmitter is called the presynaptic neuron and the target cell is the postsynaptic cell iii Communication between a neuron and its target cell is very speci c because the neurotransmitter is directed only to cells in which the neuron has close distances with 3 Hormones endocrines a chemicals released from endocrine glands into interstitial uid where they can diffuse into the blood i Hormones travel through blood to reach their distant targets ii Only cells with speci c receptors for that speci c hormone will respond and thus serve as a target cell b Neurohormones a special group of hormones that are released by a special class of neurons called neurosecretory cells Chemical classi cation of messengers A messenger s chemical structure determines its mechanisms of synthesis release transport and signal transduction hydrophobic molecules are lipid soluble and can cross the plasma membrane but do not dissolve in plasma hydrophilic molecules are water soluble and dissolve in plasma but not across plasma membranes There are 5 major classes of chemical messengers 1 Amino acid messengers a Glutamate asparate glycine GABA function as neurotransmitters in the brain and spinal chord b There are 20 amino acids that are used in protein synthesis c Amino acids are lipophobic they dissolve in water but nor across membranes 2 Amine messengers a Posses an amine group NH2 b Amines include a group of compounds called which contain a six carbon ring and are derived from the amino acid thyrosine i Ex dopamine norepinephrine epinephrine serotonin 3 Peptidesprotein messengers a Most chemical messengers are polypeptides chains of amino acids linked by peptide bonds b Hydrophilic 4 Steroid Messengers a A class of compound derived from cholesterol b They have the same function of hormones c Hydrophobic 5 Eicosanoid Messengers a They are lipids that can cross the plasma membrane b Hydrophobic Synthesis and release of chemical messengers 1 Amino Acids a Amino acids can be obtained from the diet but four of them must be synthesized by the neuron that will secrete them b Glutamate ans asparate are synthesized from glucose c Glycine is synthesized as well as GABA d Followed by their synthesis amino acid neurotransmitters are transported into vesicles wehre they are stored until they are released by exocytosis 2 Amines a All amines are derived from amino acids and all except thyroid hormones are synthesized in the secretory cell i Which amine is produced depends on the enzymes in a given cell b Catecholamines are derived from tyrosine i Thyrosine is converted into dopamine which is converted into norepinephrine and last into epinephrine ii Each one is stored in vesicles until it is needed and released by exocytosis c Serotonin i Serotonin is synthesized from the amino acid tryptophan ii Created by a pathway just like catecholamines d Histamine i Produced from histidine in the cytosol by a one step reaction ii It is also packages into vesicles stored and then released by exocytosis 3 Peptides and Proteins a Formed from a mRNA template that codes dor the amino acid sequence b Translation of this mRNA begins in the ribosomes found in the cytosol c Look at pg 130 for diagram 4 Steroids a Steroid messengers are synthesized from cholesterol in a series of reactions catalyzed by enzymes located in the smooth ER or mitochondria b lts ring structure is modi ed but the ring structure remains similar c It has hydrophobic character and can cross the plasma membrane d Because they can permeate a membrane they are not stored prior to release they diffuse out of the cell into the interstitial uid as soon as they are synthesized i They are synthesized on demand 5 Eicosanoids a Like steroids synthesized on demand and able to pass through membranes b Produced in a large pathway c Because of their roles in pain and in ammation many antiin ammatory drugs act targeting enzymes that are involved in eicosanoids synthesis Transport of messengers Once released a messenger must rst reach and then bind the receptors to the target cell for the signal to be transmitted Many times the messenger is released by the cell and acts on a cell that is close to it 0 There are enzymes in the interstitial uid that degrade these messengers to become inactive minimizing the spread of their signaling 0 Paracrine and neurotransmitters act this way Hormones are transported in blood either in dissolved form or bound to carrier proteins 0 To be transported in the dissolved form they must be hydrophilic 0 Some carrier proteins are speci c but there are others like albumins that can transport many different hormones Hydrophobic hormones are transported with carriers the amount of time it takes for half of the hormone in the blood to be degraded o Hormones in dissolved form have short half lives minutes 0 Hormones that are bound to carrier proteins are protected from degradation and have longer half lives hours 53 Signal Transduction Mechanisms Messengers transmit their signals to the receptors of the cells located on the membrane the cytosol or the nucleus o This depends on whether the messenger is capable of permeating the membrane receptors generally bind only one type or class of messengers the strength of the binding between a messenger and its receptor 0 Some receptors have more af nity towards some messengers and these are the ones that will bind rst to them 0 A single cell has many receptors for different types of messengers The magnitude of a target cell s response to a chemical messenger depends on 1 The messenger s concentration 2 The number of receptors present 3 The affinity of the receptor to the messenger o The response to the message increases as the concentration of the message increases 0 The more receptors present the more the message will bind and the stronger the response 0 an increase in the number of receptors compared to quotnormal conditionsoccurs when cells are exposed to low messenger concentrations for a prolonged period of time o a decrease in the number of receptors occurs when messenger concentraitions remain higher than normal for a prolonged period of time 0 Cells become less responsive to the messengers ligands that bind to a receptor and exert their effect 0 ligands that bind to receptors but do not produce a response they compete with the agonist of the receptor and binds to that receptor decreasing the binding of the agonist o Naloxone an opioid morphine antagonist that binds to the opioid receptors and prevents morphine from binding there and damaging tissue Signal transduction mechanisms for responses mediated by intracellular receptors 0 When hormones or lipophilic messengers bind to speci c receptors they create a response like creating proteins 0 Steps of this process for lipophilic messengers o If the receptor is located in the nucleus the hormone diffuses into the nucleus and binds to it creating a hormonereceptor complex 0 If the receptor is in the cytosol the binding occurs there creating a hormonereceptor complex and then enters the nucleus 0 In the nucleus the hormone receptor complex functions as a transcription factor by binding to a DNA region called the hormone response element HRE which is located at the beginning of a gene 0 When it binds here it activates or deactivates a gene which affects the transcription of mRNA to ultimately increase or decrease the synthesis of the protein coded by that gene 0 mRNA moves to the cytosol o The mRNA is translated by ribosomes and yield proteins 0 For steroid hormones 0 They act like lipophilic messengers but the receptors for them are called nuclear receptors 0 In order to activate a particular gene two complexes must bind to the HRE in a process called dimerization 0 After dimerization transcription and mRNA translation and proteins are created 0 For thyroid hormones 0 Same as steroid hormones but two different molecules bind to the HRE There is one of the thyroid hormone and the other is of retinoic acid derivative of vit A With these 2 different dimers the process continues Signal transduction mechanisms for responses mediated by membrane bound receptors Lipophobic messengers cannot permeate the plasma membrane and therefore their receptors are located on the plasma membrane with the binding site facing the extracellular space 0 The receptors are classi ed into 3 main categories 1 Channel linked receptors 2 Enzyme linked receptors 3 Gprotein receptors 0 Channel linked receptors 0 lons can only cross the lipid bilayer through ion channels These channels are speci c to one type of ion or class of ion to pass through them These ion channels are proteins that can be open or closed 0 ion channels that open or close in response to the binding of a chemical to a receptor or channeL Function both as receptors and ion channels The binding of a messenger causes it to open and increases the permeability for that speci c ion The opening of most ion channels produces effects by changing the electrical properties of the target cell because the ions carry a charge o a type of ligand gates channel in which the ligand is a messenger that binds to a receptor 2 types 0 1 Fast channels the receptor and channel are the same protein it causes channels to open to increase permeability of the target cell for the speci c ion Does not cause them to close Very short and fast response 0 2 Slow channels the receptor and channel are separate proteins but are coupled together by a G protein 0 A messenger binds to a protein which then releases a second messenger like calcium and then that calcium binds to another protein that casues a response 0 In the case fo G proteins a ligand binds to the G protein this causes the alpha particle to move to the ion channel causinf a conformational change that leads it to open and close 0 Longer response G protein linked ion channels are open or closed in respond to the receptor binding and stay like that for minutes 0 proteins that function both as enzymes and receptors The receptor and the enzyme are part of the same protein The messenger binds to the enzyme and activates it and this is what causes a response Most common one is tyrosine kinase 0 This catalyzes the addition of a phosphate group to the side chains of the amino acid tyrosine When the phosphate group is added then other proteins bind to it and this causes a signal transduction and a cellular response a They work by activating other proteins that are located in the membrane called Gproteins G proteins are located on the intracellular side of the plasma membrane inside where they function as links between the receptor that is bound to the three G proteins and other proteins called effector proteins G proteins have 3 subunits alpha beta and gamma In the alpha unit GDP binds and the G unit is inache Later when a messenger binds to the G protein linked receptor another protein that is bounded to the 3 little G proteins the alpha G protein releases the GDP and binds a GTP molecule to become active 0 Now that it is active the alpha subunit separates from the beta and gamma and moves to the effector causing an effect 0 Later when the ligand on the G protein receptor is released GTP loses a phosphate group and the alpha part of the subunit returns to the beta and gamma subunits and it becomes inactive The alpha part of the G protein is called a second messenger 0 Only creates a response when the ligand is bound to the g protein receptor G proteins are also cAMP cGMP inositol triphosphate diacylglycerol and calcium Signal ampli cation in chemical messenger systems 0 the ability of relatively small changes in concentration of a chemical messenger to elicit marked responses in target cells 0 One example is with cAMP When there is one messenger that binds to the receptor that then activates many alpha proteins that at the end of the process phosphorylate many proteins 0 One binding of a messenger can create a huge response 0 a series of sequential steps that progressively increase in magnitude 54 Long distance Communication via the nervous and Endocrine systems 0 The nervous and endocrine systems are specialized for long distance communications 0 Signals through the nervous system are passed from axon terminal to axon terminal They are fast and have short lives which makes them ideal for communication 0 The endocrine system lacks any direct link between the secretory cells and their target cells but it communicates through hormones Hormones travel through the blood stream to any cell in the body where they are needed 0 Hormones are released into the interstitial uid and then diffuse into the blood stream 0 The relative slowness of the endocrine system and its ability to broadcast signals over wide areas are important in coordinating metabolic activities among organ systems Chapter 6 The Endocrine System Endocrine Glands and Hormone Actions 0 There are 2 types of endocrine organs 0 Primary main function to secrete hormones Some are located within the brain hypothalamus pituitary pineal gland most are located outside of the nervous system 0 ex thyroid parathyroid thymus adrenal glands pancreas and gonads also placenta in pregnant females 0 Secondary secretion of hormones is secondary to some other function Examples heart liver small intestines stomach kidneys skin 0 Primary endocrine organs 0 Hypothalamus and Pituitary Glands Hypothalamus secretes many hormones that affect the pituitary gland the hypothalamus also has many other functions in addition to its role as an endocrine gland Pituitary gland hypophysis is a pea sized structure connected to the hypothalamus by the infundibulum Anterior lobe epithelial tissue adenohypophysis Posterior lobe neural tissue neurohypophysis Neural connection between hypothalamus and posterior pituitary o Neural ending in the posterior lobe of the pituitary secrete two peptide hormones o Antidiuretic hormone ADH Synthesized in the paraventricular nucleus Oxytocin Synthesized in the supraoptic nucleus 0 Once synthesized these are packaged into secretory vesicles Hormones neurohormones then released by exocytosis Happens through neuroendocrine re ex ADH release is stimulated by increase in plasma solute concentration 0 Target cells are in the kidneys and they respond by increasing water reabsorption Oxytocin release is stimulated by pressure in the uterus of a pregnant womansuckling by and infant Target cells are in the uterus and they respond by increasing uterine contraction or stimulating milk letdown in the breasts Blood connection between the hypothalamus and the anterior pituitary gland Anterior lobe and the cells of hypothalamus that control it primarily secrete tropic hormones hormones that regulate the secretion of other hormones Can be stimulating or inhibiting General signaling pathway quotthe hypothalamus releases a tropic hormone that effects the release of another tropic hormone from the anterior pituitary this tropic hormone then effects the release of a third hormone from another endocrine gland and this third hormone exerts effects on target cells throughout the body Anatomy of hypothalamic pituitary portal system Specialized arrangement of blood vessels two capillary beds located in a series one after the other Neurons in the hypothalamus secrete tropic hormones into capillary beds located in the median eminence of the hypothalamus 0 Travel down the infundibulum to the pituitary gland via a portal vein and then enter second capillary bed Hypothalamic tropic hormones then stimulate or inhibit the release of hormones from the anterior pituitary Portal system allows the tropic hormones to go directly to target cells in the anterior pituitary instead of returned to the heart Tropic hormones of the hypothalamus and anterior pituitary Secretion of the hypothalamic tropic hormones is regulated by neural input to the hypothalamic neurons Tropic Hormones o Prolactin Releasing Hormone PRH Stimulates anterior pituitary to release prolactin Stimulates mammary gland development and milk secretion in females 0 Prolactin Inhibiting Hormone PIH dopamine inhibits the release of prolactin o Thyrotropin Releasing Hormone TRH Stimulates the release of thyroid stimulating hormone TSH THS then stimulates the release of thyroid hormones by the thyroid gland regulate metabolism Corticotropin Releasing Hormone CRH Stimulates release of adrenocorticotropic hormone ACTH ACTH then stimulates secretion of glucocorticoids like cortisol regulates metabolism when the body is stressed from adrenal cortex 0 Growth Hormone Releasing Hormone GHRH Stimulates sectretion of growth hormone GH GH regulates growth and energy metabolism but also secretes insulin like growth factors IGF 0 Growth Hormone Inhibiting Hormone GHIH somatostatin decreases IGF release from the liver Gonadotropin Releasing Hormone GnRH Stimulates release of gonadotrophins follicle stimulating hormone FSH and luteinizing hormone LH LH stimulates ovulation and secretion of sex hormones estrogen and progesterone in females and androgens in males FSH promotes development of egg cells in females and sperm cells in males secretion of estrogen in females inhibin in both sexes Feedback loops regulate the multistep pathways by which certain hypothalamic and anterior pituitary tropic hormones are released 0 Inhibition of hypothalamic tropic hormones by anterior pituitary tropic hormones called short loop negative feedback prevents buildup of excess anterior pituitary tropic hormone o Other example CRH stimulates release of ACTH ACTH stimulates release of cortisol from adrenal gland lf cortisol levels in blood go above a certain level then the negative feedback feedback loop causes a decrease in the release of CRH and ACTH Cortisol acts to inhibit its own secretion Cortisol provides a negative feedback only to its own tropic hormones o Pineal Gland Located in brain Secrets melatonin Studies suggest this hormone is important in establishing the circadian rhythm Daylight hours suprachiasmatic nucleus inhibits melatonin secretion in the dark it is enhanced Enhances immune function suppressive effect on reproductive function 0 Thyroid Gland and Parathyroid Glands Thyroid Butter y shaped on ventral surface of trachea Secretes tetraiodothyronine T4 triiodothyronine T3 and calcitonin 0 These hormones T4 and T3 regulate body metabolism and are necessary for normal growth and development Calcitonin decreases blood calcium levels Parathyroid Smaller and located on posterior side of thyroid Secrete parathyroid hormone PTH important regulator of calcium levels in the blood works in bones kidneys and intestines o Thymus Lies close to the heart and secretes hormone thymosin lmmune cells called T lymphocytes mature here and thymosin regulates the T cell function 0 Adrenal Glands Located above the kidneys and are also called the suprarenal glands Each has cortex that takes up about 80 of the mass Epithelial tissue Inside is the medulla Made up of neural tissue Adrenal cortex has 3 layers Zona glomerulosa outer layer Zona fasciculata middle layer 0 Zona reticularis inner layer Adrenocorticoids in cortex 0 Mineralocorticoids Secreted exclusively by zona glomerulosa Aldosterone main one regulates sodium reabsorption and potassium secretion in the kidneys o Glucocorticoids Secreted mainly by zona fasciculata and reticularis Cortisol main one regulates body response to stress protein carb and lipid metabolism in a variety of tissues and blood glucose levels Cortisol regulated by CRHACTH cortisol axis 0 Sex hormones Secreted mainly by zona fasciculata and reticularis Sex hormones mainly androgens regulate reproductive function and other processes Adrenal Medulla 0 Contains chromaf n cells and secretes catecholamines o 8 of the secreted hormones is epinephrine 20 is norepinephrine less than 1 dopamine o epinephrine is secreted in times of stress or excitation O O increases heart rate and mobilizes energy stores Pancreas Both an endocrine and exocrine gland Endocrine pancreas contains cell clusters called islets of Langerhans 0 Source of 2 major hormones Insulin secreted by beta cells Decreases blood glucose levels promotes conversion to glycogen Glucagon secreted by alpha cells Increases blood glucose levels promotes glycogenolysis and gluconeurogenesis 0 There are twice as many beta cells as alpha cells Two other cell types are located in the islets of Langerhans o D cells delta cells Secrete somatostatin regulates digestion and the absorption of nutrients regulates secretion of other pancreatic hormones o F cells Secrete pancreatic polypeptide inhibits exocrine secretion of pancreas and gallbladder contractions Gonads In both sexes they produce the gametes sperm in male oocyte in female In men they secrete androgens testosterone and androstenedione In women secretes estradiol and progesterone Placenta is also an endocrine gland 0 Also secretes human chorionic gonadotropin hCG which can be used to determine pregnancy 0 Secondary Endocrine Organs O O O O 0 Heart secretes atrial natriuretic peptide ANP which regulates sodium reabsorption by the kidneys Kidneys secrete erythropoietin which stimulates the production of red blood cells by the bone marrow Organs of gastrointestinal tract secrete many hormones that are important in regulating digestion and the absorption of food These include gastrin secretin and cholecystokinin Liver secretes insulin like growth factors IGF which promote tissue growth The skin liver and kidneys are involved in the production of vitamin D3 which regulates blood calcium levels 0 Hormone Action at the Target Cell 0 Control of hormone levels in blood Concentration of hormones depends on 3 factors Rate of hormone secretion 0 0 When cells receive certain signals the rate of secretion rises or falls The faster the secretion the more hormone in blood and then more hormone receptors will be bound to target cells More hormone in blood triggers changes to target cell Some hormones like the thyroid hormones are usually secreted at steady rates so there are not many changes to target cell Hormone secretion is usually altered because of neural signal or humoral signals Each can be stimulatory or inhibitory Neural signals regulate hormones from the hypothalamus posterior pituitary and adrenal medualla Humoral signals are controlled by hormones ions or metabolites The control of blood glucose levels by insulin is an example of this type uses negative feedback 0 Another example of negative feedback is the regulation of potassium levels in blood 0 Many hormones are secreted in a pattern that goes with one s circadian rhythm All of the hypothalamic tropic hormones are affected by a circadian rhythm thereby imparting a rhythm to the release of the anterior pituitary hormones and in turn to the release of hormones affected by them Amount of hormone transported bound to carrier proteins 0 Carrier proteins increase the halflife of hormones which ensures that they are present in the blood for a longer pedod Rate at which the hormone is metabolized o Hormones remain in the blood for a relatively short time before they are metabolized 0 Once in the cell hormones are degraded by enzymes located in lysosomes Hormones free in blood can be broken down as well Can also be metabolized by enzymes in the liver The breakdown is excreted in the urine 0 Example insulin metabolism process lnsulin released from beta cells of the pancreas when blood glucose is high Acts on target cells to increase glucose transport Half life is short lasting 46 min in blood Once inside the cell insulin is exposed to insulin degrading enzyme IDE Some insulin eliminated by the kidneys o Hydrophobic hormones steroids vitamin D3 and thyroid hormones are metabolized more slowly because They are transported in blood bound to carrier proteins They can be stored temporarily in fatty tissue Hormones can then be released from these pools at a later time 0 Because of lipid solubility of steroids they can persist in the body for a couple of weeks and can be found at a later time during a blood test Abnormal Secretion of Hormones o Hypersecretionexcess secretion Example acromegaly excess growth hormone in adults 0 Hyposecretiontoo little secretion 0 In a primary secretion disorder the abnormality starts in the endocrine gland Possible cause of hypersecretion is a tumors of the endocrine cells 0 Primary hypersecretion Blood levels of tropic hormones tend to be lower than normal due to increased negative feedback from hormones regulated by tropic hormones Cortisol levels of CRH and ACTH in blood are low because excess cortisol inhibits their release through negative feedback 0 ln primary hyposecretion opposite pattern as above 0 Secondary secretion disorder Abnormality originates in the endocrine cells of either the anterior pituitary or the hypothalamus which secretes the tropic hormone lf excess ACTH is secreted from the anterior pituitary cortisol levels in the blood increase but levels of CRH fall because of increased negative feedback of cortisol lf excess CRH is secreted from the hypothalamus then blood levels of both ACTH and cortisol also increase 0 Hormone Interactions o A hormone exADH can have different receptors on different types of cells that hormone can have different effects on the body 0 In some cases the effects of the hormones oppose each other antagonism Parathyroid hormone increases blood calcium levels but calcitonin decreases them Glucagon increases blood glucose levels but insulin decreases them 0 When two hormones produce the same type of response in the body the effect can be additive net effect equals the sum of the individual effects or synergistic net effect is greater than the sum of the individual effects 0 When the presence of one hormone is needed for another hormone to exert its actions this process is called permissiveness Example epinephrine cannot trigger dilation of the bronchioles in the absence of thyroid hormone because there are no receptors to which epinephrine can bind But thyroid hormone by itself does not have a direct effect on bronchiole diameter Chapter 21 The Endocrine System Regulation of Energy Metabolism and Growth Overview of chapter Wholebody metabolism is regulated primarily by hormones Hormones that regulate bloodglucose leves insulin and glucagon Hormones that regulate growth and primary hormones that regulate wholebody metabolism thyroid hormones Glucocorticoids role in adapting to stress An Overview of WholeBody Metabolism motivation for eating is a biological process for the reason of obtaining nutrients 0 food is the sole source of energy and raw materials from which our bodies are made 0 between meals body converts energy storage carbohydrates proteins lipids to smaller molecules 0 in meals body replenishes storage by converting nutrients to energy storage molecules way body stores and utilizes energy energy metabolism 0 in uenced by eating patterns growth stress metabolic rate two concepts control energy metabolism 0 body must store nutrients during periods of intake and break them down in periods between meals 0 brain depends on glucose as primary energy so blood glucose levels must be maintained at all times between meals Anabolism o Acetyl CoA catabolized in Krebs cycle and is a substrate for triglycerides and cholesterol synthesis 0 Carbohydrates lipids and proteins eventually converted to lipids Regulation of Metabolic Pathways important factors in determining which metabolic pathways are in operation are 0 enzymes in pathways 0 compartmentation glycolysis in cytosol Krebs in mitochondrial matrix Energy Intake Utilization and Storage inside cells 3 things can happen to biomolecules o 1 broken down releasing energy to drive other processes 0 2 used as substrates to synthesize other molecules 0 3 converted to energy storage 2 primary energy storage molecules glycogen amp triglyceride Uptake Utilization and Storage of Energy in Carbohydrates o transported in blood as glucose 0 transported into cells by glucose transporters in cells glucose can be 1 oxidized for energy generate C02 and waste or 2 converted to glycogen for storage 0 if glucose levels decrease in cells glycogen broken down to glucose in glycogenolysis o stored in liver amp skeletal muscles 1 energy stored Uptake Utilization and Storage of Energy in Proteins o uptake transported as amino acids 0 once in cells 1 used for synthesis of proteins 0 or 2 catabolized for energy by proteolysis use of catabolism for energy used less than carbohydrate and lipids produces ammonia NH3 and C02 ammonia converted to urea in liver and eliminated o stored in skeletal muscle 22 energy stored Uptake Utilization and Storage of Energy in Fats o Absorbed in chylomicrons o transported in lipoproteins small proteinand lipid containing particles once target cell reached lipid must leave lipoprotein before uptake by cell trilycerides broken down from lipoproteins by enzyme lipoprotein lipase enzyme located on inside of capillaries breaks down triglyceride to monoglyceride and fatty acids 0 fatty acids go into cells monoglyceride metabolized in liver 0 stored in adipose tissue 77 total energy stored 0 fatty acids may be oxidized for energy or used to make new triglycerides stored in fat droplets in cytosol in adipocytes adipose tissue cells specialized for fat storage 0 stores triglycerides broken down to glycerol and fatty acids lipolysis catabolized for energy 0 small nutrients can be interconverted glucose can be synthesized from amino acids fatty acids synthesized from glucoseamino acids Energy Balance maintain homeostasis 0 Energy Input production utilization output Energy input work performed heat released Endocrine system regulates the body s energy balance When cells use energy they draw on stores of nutrients in cellsblood 0 Pool of nutrients is continuously replenished 2 ways 0 1 absorption of more nutrients in blood 0 2 mobilization of energy stored o catabolism of stored macromolecules into small nutrient molecules Energy Input 0 Input arrives in absorbed nutrients o Nutrients oxidized release energy Quantity is energy content Person s energy intake is total energy content Determined by calorimeter measures total amount of energy released in the form of heat as the substance burns 0 Fat has a higher energy content than carbohydrates and protein Most ef cient form to store energy Energy Output 0 Energy released during oxidationcatabolic reactions as heat and work 40 energy used to form ATP to perform cellular work rest of energy takes the form of heat 0 energyrequiring processes classi ed into 3 categories 1 mechanical work 0 uses intracellular protein laments to generate movement 0 EX muscle contraction 2 chemical work 0 forms bonds during chemical reaction 0 used to synthesize large molecules 3 transport work 0 moves a molecules from one side of the membrane to the other o EX NaK pump or vesicular transport endoexocytosis Metabolic Rate 0 Metabolic rate amount of energy so expended per unit time in the body In uenced by muscular activity age gender body surface area environmental temperature 0 Basal metabolic rate BMR 9 rate of energy expenditure of a person who has fasted for at least 12 hrs and is awake lying down physically and mentally relaxed Both metabolic rate and work are minimal in these conditions BMR increases as body weight increases BMR in growing children is greater and lower in elderly Negative and Positive Energy Balance 0 When energy is taken in at a rate greater than expended quantity of stored energy increases positive energy balance 0 When energy is taken in less than the rate it is expended quantity of stored energy decreases negative energy balance Energy Metabolism During the Absorptive and Postabsorptive States maintaining energy balance requires energy inputenergy output absorptive state 34 hours after a typical meal when nutrients are absorbed 0 time absorption stops until the next meal 0 at this time energy input gt energy output positive energy balance postabsorptive state time between meals when nutrients are not being absorbed 0 energy output gt energy intake the body uses energy sources from fatty acids to spare the glucose for the central nervous system during the absorptive state energy is stored in macromolecules during the postaborptive state energy stores are mobilized Metabolism During the Absorptive State 0 Primarily an anabolic state synthesis of macromolecules Body Cells in General 0 Body s energy need supplied primarily by glucose plentiful after a meal 0 Proteins are not synthesized as storage molecules 0 Body cells catabolize proteins for energy only under extreme conditions Skeletal Muscle Cells 0 Take up glucose and amino acids from blood 0 Skeletal muscles convert glucose to glycogen for storage Liver Cells 0 Converts nutrient molecules to energy stores that can supply energy Converts glucose to glycogenfatty acids Converts fatty acids to triglycerides Transported to adipose tissue for storage converts amino acids to keto acids 0 act as intermediates in glycolysis and Krebs cycle keto acids used to synthesize amino acids to then be converted to triglycerides 0 very low density lipoproteins VLDLs particles where triglycerides are packaged to transport them to adipose tissue plasma membrane of most cells have enzyme lipoprotein lipase catabolize triglycerides off lipoproteins to fatty acids and monoglycerides they then diffuse into the cellconverted back to tiglyceride Adipocytes 0 Store energy in the form of triglyceridesfat o Chylomicrons transport triglycerides to adipocytes 0 Excess glucose enters adipocytes or converted to triglycerides Energy Reserves 0 Triglyceride synthesis nal pathway for all nutrients absorbed in excess 0 Triglyceride synthesis best way to store most energy in least weight 0 Glycogen 1 storage 0 Protein 2025 0 Fat 7580 Metabolism During the Postabsorptive State absorption of nutrients stops after a few hours after a meal without nutrients body catabolizes glycogen protein and fat for energy Postabsorptive state primarily catabolic state 0 Primary function of this state is to maintain plasma glucose levels Gluconeogenesis body synthesizes new glucose from amino acids glycerol and other breakdown products of catabolism Glucose sparing tissue primarily uses fat for energy conserving glucose for use by the central nervous system Body Cells in General 0 Most cells utilize fatty acids not glucose for energy sparing glucose for the CNS Skeletal Muscle Cells 0 Glucose formed from glycogen during glycogenolysis for energy can only be used within that muscle cell Glycogen catabolized to glucose6P Phosphate group cannot be removed form glucose because skeletal muscle cell lacks enzyme glucose6phosphotase Glucose formed by glycogenolysis remain in cell until catabolized by glycolysis to pyruvatelactate Any lactate goes to the liver for processing Liver Cells 0 Primary source of plasma glucose during postabsorptive state 0 Glycogen stores broken down by glycogenolysis to glucose 6P and enzyme glucose6phosphotase catalyzes to glucose Then transported to the blood Liver glycogen stores unlike skeletal muscle stores can be mobilized to provide the blood with glucose 0 Primary site of gluconeogenesis o Ketogenesis occurs in the liver Ketogenesis some of the fatty acids are converted to ketone bodies which are released into the blood and catabolized by most tissue Production of ketones important in fasting CNS uses ketones for energy in this case Adipocytes o Supplies fatty acids to the blood for energy sparing glucose for CNS 0 Catabolizes stores triglycerides to glycerol and free fatty acids Regulation of Absorptive and Postabsorptive Metabolism transitions between absorptive and postabsorptive states marked by alterations in metabolic activities in tissue triggered primarily by endocrine signals involving pancreatic hormones insulin and glucagon The Role of Insulin lnsulin peptide hormone secreted by beta cells located in the pancreatic islets of Langerhans Insulin promotes the synthesis of energy storage molecules and other processes characteristic of the absorptive state Insulin is an anabolic hormone Its secretion is stimulated by signals associated with feeding and absorption of nutrients Factors Affecting Insulin Secretion O O Insulin secretion is absorptive period increases plasma insulin levels promoting metabolic processes Insulin secretion decreases in postabsorptive state decreasing plasma concentration of insulin which turns off absorptive processes During absorptive period Plasma glucose levels increase Increase secretion of insulin HOW 1 Glucose enters beta cells by facilitated diffusion using GLUT2 transporter o Catabolized to generate ATP which closes potassium channels Less potassium moving out beta cells become depolarized This opens calcium channels Calcium enters the cell triggering exocytosis of insulin 0 2 Insulin secretion is also in uenced by plasma amino acid concentration 0 Increase in plasma amino acids generate ATP through Krebs cycle and oxidative phosphorylation and ATP close potassium channels Process continues as above 0 3 hormones and autonomic nervous system in uence secretion of insulin 0 secretion stimulated by glucose dependent insulinotropic peptide GIP and glucagonlikepolypeptide 1 GLPl both hormones secreted by small intestine o parasympathetic nerve activity also increases insulin secretion o parasympathetic activity GIP and GLP1 all increase in response to the presence food trigger insulin secretion in advance of rising plasma glucose levels 0 During postabsorptive period Plasma glucose levels decrease Turns off insulin secretion Sympathetic nervous activity and epinephrine inhibit insulin secretion Actions of Insulin o In uences all aspects of energy metabolism 0 1 Promotes energy storage by synthesis of fatty acids and triglycerides in the liver and adipose tissue glycogen in liver and skeletal muscles proteins in most tissues 0 2 opposes catabolism of energy stores inhibiting the breakdown of proteins triglycerides and glycogen o 3 suppresses gluconeogenesis by the liver 0 4 stimulates uptake of amino acids which facilitates hormone s stimulatory effect on protein synthesis 0 5 stimulates uptake of glucose by increasing number of glucose transporters GLUTl through GLUT13 GLUT4 only transported sensitive to insulin 0 A facilitated diffusion transporter for glucose and glucose transporter for wholebody metabolism 0 Found in adipose tissue and skeletal muscle in vesicles in cytosol o lnsulin triggers insertion of transporters into plasma membrane by exocytosis or the synthesis of new transporters transport of glucose to CNS not affected by insulin 0 6 insulin has important growth promoting effects must be present in the blood for growth hormone to work it is permissive does not actually stimulate growth 0 insulin promotes reactions associated with absorptive state and suppresses reactions of postabsorptive state The Role of Glucagon o Glucagon peptide hormone secreted by alpha cells of pancreatic islets of Langerhans o Insulin and glucagon are antagonists o Glucagon promotes processes of the postabsorptive state 0 Secretion decreases during absorptive and increases in postabsorptive Factors Affecting Glucagon Secretion o Signals that stimulate secretion of glucagon 1 decrease in blood glucose suppress insulin 2 sympathetic nervous activity and epinephrine suppress insulin Actions of Glucagon o Opposes insulin s actions 0 1 in the liver promotes glycogenolysis decreases glycogen synthesis gluconeogenesis increases blood glucose ketone synthesis breakdown of proteins 0 decreases protein synthesis 0 2 in adipose tissue stimulates lipolysis suppresses triglyceride and protein synthesis 0 glucagon is a catabolic hormone INSULIN SECRETION Most tissues Adipose tissue Liver and Liver muscle Increases glucose Increases fatty acid Increases glycogen Increases fatty acid uptake except and triglyceride synthesis and triglyceride brain liver synthesis syntehsis exercising muscle Increases amino Decreases lipolysis Decreases Decreases acid uptake glycogenolysis gluconeogenesis Increases protein synthesis Decreases protein breakdown GLUCAGON SECRETION Liver Adipose tissue Increases glycogenolysis Increases lipolysis Decreases glycogen synthesis Decreases triglyceride synthesis Increases gluconeogenesis Increases ketone synthesis Increases protein breakdown Decreases protein syntehsis FACTORS AFFECTING INSULIN AND GLUCAGON RELEASE Factor I Effect on insulin I Effect on glucagon secretion secretion Increase plasma glucose Increase Decrease Increase plasma amino Increase Increase acids Increase plasma GIP Increase Increase Increase parasympathetic Increase Increase activity Increase sympathetic Decrease Increase activity Increase plasma Decrease Increase epinephrine Negative Feedback Control of Blood Glucose Levels by Insulin and Glucagon fastin blood glucose levers greater than 140 mgdL hyperglycemia o hyperglycemia indicative of diabetes mellitus a serious and increasingly common disease involving defects in insulin productionsignaling fasting blood glucose levels below 60 mgdL hypoglycemia o affects NS insulin and glucose together control plasma glucose concentration through negative feedback 0 an increase in plasma glucose increases insulin secretion and decreases glucagon both decrease plasma glucose 0 a decrease in plasma glucose concentration decreases insulin and increases glucagon both increase plasma glucose insulin decreases plasma glucose in 3 ways 0 1 promoting uptake of glucose into cells by increases GLUT4 transporters on membrane 0 2 reducing concentration of free glucose in cell by converting it to glycogen promotes glucose uptake and increases size of glucose concentration gradient 0 3 suppressing gluconeogenesis reduces rate of new glucose released to blood 0 if plasma glucose decreases insulin secretion decreases causing an increase in plasma glucose decrease in plasma glucose stimulates glucagon secretion to increase plasma glucose glucagon increases plasma glucose by 0 1 promoting gluconeogenesis o 2 glycogenolysis in the liver directly increases plasma glucose by stimulating lipolysis in adipose tissue providing fat as alternative energy Stimulation of Insulin and Glucagon Secretion by Amino Acids 0 Increase in plasma amino acids stimulates release of insulin and glucagon 0 Rise in amino acids stimulates insulin secretion Promotes increase in amino acid uptake by cells Rise in insulin promotes decrease in plasma glucose 0 Rise in plasma amino acids stimulates secretion of glucagon Promotes increase in plasma glucose Effects of Epinephrine and Sympathetic Nervous Activity on Metabolism sympathetic nervous system and epinephrine suppress insulin and promote glucagon secretion 0 promoting metabolic adjustment to postabsorptive state postabsorptive period characterized by decreased plasma glucose levels 0 increase glucagon secretion and decrease insulin decrease on plasma glucose acts on glucose receptors in CNS to raise activity in sympathetic neurons 0 this triggers epinephrine secretion 0 epinephrine acts on liver to increase gycogenolysis and gluconeogenesis o epinephrine acts on skeletal muscles to increase glycogenolysis o epinephrine acts on adipose tissue to increase lipolysis importance of sympathetic in uence on metabolism is apparent in body s reaction to stress general term for any condition that actuallypotentially poses serious challenge to the body s ability to maintain homeostasis o stressors trigger ght or ight responses 0 elevates plasma glucose levels due to increase in gluconeogenesis and glycogenolysis in the liver 0 elevates plasma levels of fatty acids and glycerol due to increase of lipolysis in adipocytes diseases of body metabolism most apparent in diabetes mellitus PA RT 2 o Thermoregulation o Humans are less affected by changes in the ambient temperature because we have the ability to maintain our body temperatures within a narrow range through the process of thermoregulation Animals with this ability homeothermic Animals without this ability poikilothermic 0 Temperature Balance Humans can control body temp by regulating the rates by which heat is produced and lost by the body 0 Negative heat balance 0 Heat loss exceeds heat produced 0 Hypothermia too cold 0 Causes stupor loss of consciousness multiple organ failure death 0 Positive heat balance 0 Heat produced exceeds heat lost 0 Hyperthermia too hot 0 Causes loss of consciousness convulsions respiratory failure death 0 Mechanisms of heat transfer between the body and external environment Heat is lost by four mechanisms 0 Radiation 0 Thermal energy is transferred from the body to the environment in the form of electromagnetic waves 0 Ex outside in the cool air you emit radiant energy to the air molecules around you which in turn makes your body colder If the body is colder than the surroundings then it gains heat by absorbing the energy of the environment sitting at a camp re Conduction 0 Transfer of thermal energy between objects that are in direct contact with each other 0 Ex touch cod metal you feel coder o Evaporation 0 Heat is lost from an object through evaporation of water from its surface Water evaporates from the skin the lining of the airways and other moist surfaces like the lining of the mouth 0 lnsensibe water loss occurs without you being aware of it and happens continuously o Sensible water loss occurs as your body needs it Sweat from the sweat glands 0 When the environment is warmer than body temp radiation and conduction transfer heat into the body and the body must rely on evaporation to make that heat go away Sweating cools the body In a humid environment sweating is not as efficient because water cant evaporate into the already watery air Convection o The transfer of heat from one place to another by a moving gas or liquid 0 Contributes to heat loss on a windy day responsible for wind chill factor Conductive and evaporative heat loss increase because the blanket that slows down the rate of heat loss is made thinner 0 Regulation of Body Temperature The body s thermoregulatory efforts work to maintain the core temperature of the body 0 Central nervous system abdominal and thoracic cavities 37 degree C or 986 degree F thermoregulatory center is in the hypothalamus input about core temp is received from central thermoreceptors 0 these are important to return core temp to normal other thermoreceptors peripheral thermoreceptors located on the skin and detect temp on the skin usually below core temp and more variable 0 our bodies do not regulate this temperature but use the info to have us make behavioral adjustments 0 ex wear a sweater Thermoregulation in the Thermoneutral Zone 0 The primary mechanism to regulate body temp is to vary the amount of blood owing to the skin this is where thermal energy in the blood can be exchanged with the environment 0 When body temp decreases blood ow to skin decreases Blood loses less heat to environment 0 When body temp increases blood ow to skin increases Blood loses more heat to environment 0 Changes in blood ow work to maintain temp when it is within the thermoneutral zone 2530 degree C of environmental temp The sympathetic nervous system regulates blood ow based on input of the thermoregulatory center 0 When body temp decreases sympathetic activity to the arterioles increases causing vasoconstriction and thereby decreasing cutaneous ow to conserve body heat 0 When body temp increases sympathetic activity to the arterioles decreases causing vasodilation and thereby increasing cutaneous ow to transfer to the environment When the temp is outside of the Thermoneutral zone other measures must be used Heat Generation in a Cold Environment When environmental temp is below 25 degree C simply decreasing blood ow cannot stop the temp from falling The heat promoting center of the hypothalamus communicated to effector organs to stimulate shivering and decrease sweat production 0 Shivering thermogenesis Rapid rhythmical contractions of skeletal muscles controlled by spinal re ex This generates heat Human infants and hibernating animals can generate heat through nonshivering thermogenesis 0 Brown adipose tissue generates heat through uncoupling of electron transport chain Energy released by electrons is lost as heat and not used to make ATP 0 Adult humans have little if any brown adipose tissue Heat Loss in a Warm Environment When environmental temp goes above thermoneutral zone body must produce sweat for evaporative heat loss 0 Average person has 25 million sweat glands 0 Two types Eccrine Glands More common and located all over the body mainly forehead palms of hands and soles of feet 0 Empty into pores of the surface of skin 0 Active at birth 0 Primary secretion of water sodium and chloride and some potassium As sympathetic activity warm environment or ght or ight increases so does sweat production Apocrine Glands o Mainly in axial and analgenital region 0 Empty into hair follicles Do not become active until puberty Has what eccrine sweat has in addition to proteins and fatty acids 0 This allows bacteria to growcauses odor o Alterations in the Set Point for Thermoregulation Fever During infection white blood cells produce cytokines that function as pyrogens chemicals that induce fever 0 This is bene cial because it helps body defend itself Fever is induced through actions on the thermoregulatory center adjusts the temp Body responds by increasing heat production and minimizing heat loss 0 Person appears white less blood ow and shivers May feel cold even though person is warm there are contradictory neural signals Hormonal Regulation of Growth 0 Body Growth Post natal growth occurs in rst 2 years of life After 2 years old growth occurs at a slower rate until beginning of adolescence and puberty pubertal growth spurt begins During periods of growth size and number of cells in the body s soft tissue increases length and thickness of bones changes too especially legs and vertebral column Body growth in childhood Regulated by hormones but also in uenced by genetic makeup diet disease and stress 0 Mainly Growth Hormone GH from anterior pituitary o Other hormones insulin thyroid hormones and sex hormones 0 Growth of various tissues and organs is in uenced by many growth factors and growth inhibiting factors Ex nerve growth factors promote elongation and proliferation of axons and dendrites of neurons 0 Effects of Growth Hormone In children GH effects bones and soft tissue that then results in body growth In adults it maintains bone mass and lean body mass body weight contributed to muscle How it promotes growth Stimulates protein synthesis therefore increases cell size hypertrophy o Stimulates cell division therefore increasing cell number hyperplasia 0 These 2 result in linear growth GH indirectly promotes a number of actions that affect growth Increases plasma concentration of glucose fatty acids and glycerol 0 lnhibits glucose uptake in adipose tissue and skeletal muscle 0 Stimulates lipolysis and gluconeogenesis Energy is then more readily available to tissues Promotes increase uptake of amino acids Diet is also necessary for growth need a lot of proteins 0 Body does make proteins but some can only be received through diet some essential amino acids 0 Also need calcium in the diet for bone growth 0 Energy content calories of diet must meet the demands of growth Many of the growth promoting effects of GH result from the actions of intermediary chemical messengers on target Ussues o lnsulin like growth factors lGFs o lGF2 for gestational growth 0 lGF1 growth following birth 0 GH stimulates the production of lGFs by the liver Factors Affecting Growth Hormone Secretion Secretion of GH is regulated by 2 hypothalamic hormones 0 Growth Hormone Releasing Hormone 0 Growth Hormone Inhibiting Hormone somatostatin GH is regulated through negative feedback loops short loop negative feedback 0 lGF s exert long loop negative feedback controls on the hypothalamus and anterior pituitary to inhibit GHRH and GH GHRH secretion is affected by plasma nutrient concentrations 0 GH secretion is also stimulated in response to exercise stress or sleep 0 This is useful because it tends to counteract reduced plasma levels of glucose and fatty acids thereby helping to maintain a steady supply of these much needed energy sources 0 The signi cance of secretion during sleep is unknown 0 Daily plasma levels of GH reach a maximum at puberty Bone Growth 0 Bone is an important reserve for calcium 0 To support the body the bone must be strong and not brittle O O Hydroxyapatite gives bone a mineral component that helps it withstand compressive forces Osteoid gives bone its ability to withstand tensile or stretching forces making it less prone to fracture Bone has a dynamic nature 0 0 Is able to grow throughout childhood and repair itself when fractured Can also change its thickness and strength when a person is usually involved in heavy lifting person who lifts heavy weights at the gym often Restructuring of bone is called remodeling Osteoblast and osteoclasts work in remodeling Osteoblasts bone makers Build up the mass of bone tissue through depog on Osteoclasts bone breakers Break down bone tissue through resorption Bone growth occurs when work of osteoblasts is more than osteoclasts Osteoblasts initiate bone deposition by laying down the osteoid and then deposition of calcium phosphate calci cation 0 As osteoblast works to build bone it is immobilized and becomes and osteocyte has long lamentous processes called canaliculi 0 These cells communicate through gap junctions Good because interior of bone tissue can exchange nutrients waste and other minerals within blood vessels Osteoclasts affect resorption because secretes acid that dissolves calcium phosphate crystals and enzymes that break down osteoid Releases calcium and phosphate to bloodstream In bones of growing children epiphyseal plate composed of cartilage plays a key role in elongating bones Inside of bone 0 Red marrow produces red and white blood cells 0 Yellow marrow contains adipocytes With GH bones increase in circumference 0 When increasing length Begins with activity of the cells in the epiphyseal plate called chondrocytes like osteoblasts but produce cartilage and not bone As new cartilage forms chondrocytes adjacent to the shaft die and osteoblast replace them convert cartilage to bone In late adolescence epiphyseal plate closure happens 0 At this point GH can no longer stimulate bone elongation Effects of Abnormal Growth Hormone Secretion o De cient GH dwarfism 0 Growth stunted poor muscles development high body fat 0 Can be caused by de cient responsiveness to GH which can come from defective GH receptors insufficient lGF s or failure to respond to lGF s Excessive GH secretion before plate closure gigantism o Abnormally large but body is proportioned Excessive GH secretion after plate closure acromegaly o Dis guration of certain body parts Overly wideprotruding jaw Long limbs o Other Hormones that Affect Growth lnclude thyroid hormones sex hormones and insulin Thyroid hormones are required for GH to exert its effects on target tissues lnsulin is required for secretion of lGF1 and for normal protein synthesis in general Sex hormones are low until around puberty 0 Promote growth by stimulating GH and lGF1 Stop bone growth by closing plate Androgens also promote growth 0 Ex testosterone causes rise in muscles mass High concentrations of glucocorticoids secreted from the adrenal cortex decease growth 0 Promote resorption and protein catabolism This is stimulated more with stress Thyroid hormones 0 Show little variation and want to just stay steady 0 Synthesis and Secretion of Thyroid Hormones Has numerous follicles ln interstitial space there are C cells which produce cacitonin Thyroglobulin T6 is the primary protein found in the colloid and is the precursor molecule for TH 0 Also in the colloid are enzymes required for TH synthesis 0 All components for TH synthesis are located in the colloid Steps of TH synthesis 1Tyrosine residues of T6 are iodinated 0 One iodine monoiodotyrosine MIT o Tow iodines diiodotyrosine DIT 2Two iodinated tyrosine residues on the same TG molecule are coupled 0 two DlT groups T4 0 DIT and MIT T3 0 3 Thyroid hormones are stored in colloid and bound to T6 for up to 3 months 0 4 TSH binds to receptors and activates cAMP o phosphorylation of follicular cell proteins necessary for the release of thyroid hormones happens 0 5 follicular cells take in iodinated TG molecules from the colloid through phagocytosis 6 phagosome fuses with a lysosome 7 Exposure of T6 to lysosome triggers release of T3 and T4 to the follicular cell 0 diffuse across barrier and into the bloodstream o bound to protein carriers that include thyroxine binding globulin transthyretin and albumin T4 produced and secreted 10 times greater than T3 but T3 4 times more potent Most of the T4 is eventually converted by the liver kidneys or target tissues into T3 this process called activation TH secretion is stimulated by TSH which is stimulated by TRH thyrotropin releasing hormone T4 provides a stronger negative feedback than T3 The only known stimulus for TRH secretion is exposure to cold temperatures o Happens more in infants than in older children and rarely in adults TRH secretion is inhibited by stress 0 Actions of Thyroid Hormones Thyroid hormones are lipophilic so they easily cross membranes Binding of TH to receptors alters rate of transcription of mRNA from DNA thereby altering protein synthesis Primary action of TH is to raise body BMR Increase rate of oxygen consumption and energy expenditure at rest 0 Heat generation increases calorigenic effect 0 The increases of metabolism occur throughout the body except the brain spleen and gonads Ways that TH increases metabolism Increases the rate of the NaK pump Promotes increased numbers of mitochondria in cells Increases the concentration of certain enzymes involved in oxidative phosphorylation In higher than normal concentrations 0 TH promotes increased energy mobilization Enhances glycogenesis conversion of muscle proteins to amino acids and ipoysis Gluconeogenesis and ketone synthesis In lower than normal conditions 0 TH has opposite effect TH permits many tissues to respond to sympathetic neural input and to circulating epinephrine TH de ciency In infants can lead to irreversible brain damage called cretinism o Retarded development and stunted growth 0 Can be prevented by early diagnosis of hypothyroidism and T3 replacement therapy 0 In adults 0 Impairment of mental function but is reversible Glucocorticoids 0 Factors Affecting Secretion of Glucocorticoids Secretion is stimulated by adrenocorticotropic hormone ACTH which is stimulated by corticotropin releasing hormone CRH Glucocorticoids are lipophilic so they diffuse out of the adrenal cortex and into the blood stream immediately after synthesis Regulated by negative feedback which limits the feedback of CRH and ACTH Cortisol the primary glucocorticoid is secreted in bursts and has a circadian rhythm 0 Higher levels in the morning and lower at night 0 Stress stimulates cortisol secretion 0 Actions of Glucocorticoids Their presence is essential to body ability to mobilize fuels in response to signals from other hormones Maintain normal concentration of enzymes necessary for breakdown of proteins fats and glycogen and for the conversion of amino acids to glucose in the liver 0 Necessary for survival during fasting Also required for GH secretion 0 Effects on functions of the immune system nervous system and kidneys Plasma levels of glucocorticoids increases 0 Decrease uptake of glucose and amino acids 0 Stimulate lipolysis in adipose tissue raises plasma levels of fatty acids and glycerol 0 Stimulate protein breakdown in muscles and other Ussues Glucocorticoids are given therapeutically o For arthritis and allergies 0 During tissue transplant to decrease likelihood of rejection 0 The Role of Cortisol in the Stress Response Ability to tolerate stress is poor in glucocorticoid de cient people Other changes associated with stress include increased secretion of antidiuretic hormone by the posterior pituitary increased renin release by the kidneys and elevated plasma levels of angiotensin II 0 Help maintain blood pressure when stressed 0 Effects of Abnormal Glucocorticoid Secretion An excess or de ciency can result from a defect originating in the adrenal cortex or a defect in secreting tropic hormones CRH or ACTH Hypersecretion Cushing s syndrome 0 Hyperglycemia and protein depletion 0 Muscle wasting weakness fragility because of breakdown of connective tissue 0 Bruise easily because of weakened blood vessels 0 Unusual pattern of body fat distribution abdomen shoulder blades face Hyposecretion Addison s disease 0 Hypoglycemia and poor tolerance of stress 0 Defect in the secretion of aldosterone 0 Excessive sodium secretion and potassium retention Can result in cardiac arrhythmias and neuromuscular signs