Biochemistry Exam 1 Study Review
Biochemistry Exam 1 Study Review BMB 401
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Popular in Biochemistry
This page Study Guide was uploaded by Laura Brito on Monday February 15, 2016. The Study Guide belongs to BMB 401 at University of Miami taught by Dr. Amjad Farooq in Spring 2016. Since its upload, it has received 151 views. For similar materials see Biochemistry for the Biomedical Sciences in Biochemistry at University of Miami.
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Date Created: 02/15/16
Part 1 Lipids and Carbohydrates 11 Life 11a Fundamental characteristics Vocabulary 1 Biochemistry the study of chemical biochemical and physical biophysical processes driving living organisms at molecular level 2 LifegtDomaingtKingdomgtPhylumgtClassgtOrdergtFamilygtGenusgtSpecies 3 Two major domains of the phylogeneticevolutionary tree of life Prokaryotes Bacteria and Archaea and Eukaryotes 4 Biological molecules constructed from a limited number of chemical elements C N O and H being the bread and butter of life a Other elements include Ca P K S Cl Na and Mg b Plethora of trace elementsltO1 o Fe Zn Cu Mn 5 Chemical evolution simple compounds condense to form more complex molecules and polymers 6 Selfreplicating molecules subject to natural selection inherent ability to adapt to environmental pressures 7 Adapt to changeadjust make fit for or change when environment changes 8 Adopt to take onup ex protein adopts 3D fold under physiological conditions 9 Prokaryotes unicellular organisms lack nucleus and rarely harbor membranebound organelles DNA loose Protein Ribosome Transcription Factor Inner membrane Outer membrane protectiontransport Flagellum motilitysensor 10 Eukaryotes unicellular and multicellular organisms harbor a nucleus and are further characterized by numerous membranebound organelles 11 Combartmentalization promotes efficiency by maintaining high local concentrations of reactants D WDPPP39ED Smooth endoplasmic reticulum lipid metabolism Rough endoplasmic reticulum studded with ribosomes protein synthesis Nucleolus within nucleus rRNA synthesis Chromatin skeletal structure of the cell Nucleus Nuclear Membrane Vacuole Water storage in plants Centrioles Golgi Apparatus secretory pathway Mitochondrion power plant Lysosome digestive enzymes x39r39 Dczocrsgt Cell membrane 12 Condensation Reaction one in which two functional groups ex carboxylate and amino combine to form a larger molecule usually resulting in the loss of water or other small molecule 13 Carboxvlic AcidAmine reactions polymerization of amino acids into polypeptide chain amongst others 14 Hydrolysis splitting up a larger molecule into constituent parts or cleavage of a chemical bond with the addition of water 15 ATP hvdrolvsis required to release free energy 16 lonic interactions salt bridges between oppositely charged groups form the basis of the functional diversity and elasticity of life 17 Macromolecules composed of functional groups that are complementary enables them to recognize and orient each other 18 Complementaritv basis of macromolecules to be able to selfreplicate and produce exact replicas of themselves evolutionary advantage and are thus naturally selected 19 Protein Dolvoeptide composed of amino acids 20 Nucleic Acid Dolvnucleotide composed of nucleotides 21 Polvsaccharide complex carbohydrate composed of monosaccharides simple carbohydrates 11 b Thermodynamic Principles Vocabulary 1 Thermodvnamics changes in heat and temperature as related to energy exchange and work done by physicochemical as well as living systems 2 Four Laws of Thermodvnamics O to 3 1st and 2nd laws are of particular relevance to understanding living systems 3 Natural processes are Spontaneous deltaSgtO a increase in entropy s b decrease in free energy deltaG energy available to do useful work at constant temperature pressure and pH Hypothesis a plausible statement that needs to be tested thoroughly Theory a principle that has been thoroughly tested and applied Law fundamental rule that is universally true Entropy measure of the disorder in a system increased entropy is increased disorder Equilibrium deltaG 0 Death living organisms maintain steady state A B c C dAdt rate of decay breakdown of A into C dCdt rate of decay breakdown of C into A and B Forward reaction is exactly balanced by reverse reaction dAdt dCdt Concentration of C also stabilizes at equilibrium 9 Steadvstate Life rates of synthesis and degradation of metabolic intermediates within a cell are more or less equal such that their concentrations change little over time irrespective of how much food and water are consumed a A B c C b C D ltgt E c dC1dt rate of formation synthesis of C from A and B 90gt eeces d dC2dt rate of decay breakdown of C into E e Rate of synthesis of C equals its rate of breakdown f dC1dt dC2dt g Concentration of C also stabilizes but under steadystate conditions neither of the above reactions has to be at equilibrium 10 First Law of Thermodvnamics energy is neither created nor destroyed but only conservedexchanged a deltaU q w b delta U change in internal energy of the system c q heat exchanged or added d w work done 11 Second Law of Thermodvnamics natural processes are spontaneous delta SgtO leading to an increase in disorder or entropy S a delts Suni delts Ssys delta Ssur gt O 12 Gibb s Free EnerClV Equation biological manifestation of the first and second laws of thermodynamics a measure of the thermodynamic potential of a biological process to do useful work deltaG39 deltaH39 T deltaS39 deltaG39 change in free energy calmol deltaH39 change in enthalpy calmol deltaS39 change in entropy Kcalmol e T absolute temperature K 13 Biolooical processes overall accompanied by a decrease in free enerqv deltaG lt O a Endergonic processes deltaG gt O are coupled to exergonic reactions deltaG lt O b Endothermic processes deltaH gt O are driven by an increase in entropy TdeltaS gt0 they are under entropic control 906 delta H delta S delta G delta H T deltaS Enthalpically favored exothermic and Entropically favored Spontaneous exergonic at all temperatures Enthalpically favored but entropically opposed Spontaneous only at temperatures below T deltaH deltaS Enthalpically opposed endothermic but entropically favored Spontaneous only at temperatures above T deltaH deltaS Enthalpically and Entropically opposed Nonspontaneous endergonic at all temperatures c Thermodynamically favorable reactions deltaG lt O are described as being unden i Enthalpic Control deltaH lt O and TdeltaS lt 0 ii Entropic Control deltaH gt O and TdeltaS gt O iii Enthalpic and Entropic Control deltaH lt O and TdeltaS gt 0 14 Change in free energy of the reaction delta G under nonequilibrium setting is given by deltaG deltaG39 RTaneq a deltaG39 change in free energy of all species under standard state calmol b R universal molar gas constant 199 calmolK c T Absolute temperature K d Keq equilibrium association constant MA1 i Keq CAB concentration of each species equilibrium ii Rewritten as deltaG39 RTaneq Questions 1 Discuss the differences between prokaryotes and eukaryotes Prokaryotes contain both bacteria and archaea Prokaryotes are unicellular organisms They lack a nucleus and rarely harbor membranebound organelles Eukaryotes include both unicellular and multicellular organisms They harbor a nucleus and are further characterized by numerous membranebound organelles Compartmentalization promotes efficiency by maintaining high local concentrations of reactants 2 Make a list of the major eukaryotic organelles and their functions Outer Membrane protectiontransport Flagellum motilitysensor Smooth ER lipid metabolism Rough ER protein synthesis it is studded with ribosomes Nucleolus rRNA synthesis Mitochondria power plant of the cell Golgi Apparatus secretory pathway Lysosomedigestive enzymes 3 Which four elements occur in Virtually all biological molecules 0 Carbon 0 Nitrogen 0 Oxygen 0 Hydrogen 4 Draw a simple condensation and hydrolysis reaction 5 Name the building blocks of proteins carbohydrates and nucleic acids 0 proteins amino acids 0 carbohydrates monosaccharides O nucleic acids nucleotide 6 Summarize the relationship between energy U heat q and work w AUzqw where the internal energy of a system is depended upon the heat added or exchanged and the work done by the system to the surrounding 7 State the first and second laws of thermodynamics First Law of Thermodynamics Energy is neither created nor destroyed but only conservedexchanged Second Law of Thermodynamics Natural processes are spontaneous leading to an increase in the disorder entropy 8 EXplain why changes in both enthalpy and entropy determine the spontaneity of a process AG AH TAS where AGO change in free energy AGO gt O endothermicendergonic AGO lt O exothermicexergonic remember AHO lt O enthalpic control exergonic and TASO gt O entopic control 9 What is the free energy change for a reaction at equilibrium AG RTaneq because AG0 10 Write the equation showing the relationship between AGquot and Keq AG AGO RTaneq 11 Write the equation showing the relationship between AG AGquot and the concentrations of the reactants and products AG AGO RTlnC A B 12 EXplain how biochemists define the standard state of a solute Temperature T 25C Pressure P latm pH 70 neutral 12 Water 12a Physical Properties Vocabulary 1 Two major forces acting on biological molecules NonCovalent a Ionic interactions between oppositely charged ions strongest non covalent b Van der Waals Forces ex Hbonding dipolar interactions 2 Hvdroohobic effect the exclusion of nonpolar groups from polar surroundings so as to maximize the entropy of water molecules 3 Amphiphilic substances can form micelles or bilayers so as to shield their hydrophobic groups while exposing their hydrophilic groups to water by hydrophobic effect 4 Osmosis process by which water diffuses across permeable membranes from a region of high concentration to a region of low concentration 5 Dialysis solutes diffuse across a semipermeable membrane from regions of higher concentration to regions of lower concentration 6 Van der Waals envelooe or surface the approximate boundary or the perimeter of a molecule as demarcated by the outer boundary of the surrounding cloud of electrons 7 Van der Waals radius the distance from the center of the molecule to the Van der Waals envelope 8 Van der Waals radius of water 14A39 two water molecules cannot get closer to each other than 2r distance from the center of one molecule to the center of the other 9 Dipoles charge separation 10 Van der Waals forces interactions between oppositely charged ends of dipoles a DipoleDipole interactions interactions between permanent dipoles such as a CO group i Hvdrooen Bonding dipolar interaction between an electropositive H atom bonded to a highly electronegative atom such as O or N and another highly electronegative atom 1 Rather strong nature and ubiquitous in biological systems 2 Supreme attractive force that renders water a liquid at room temperature b DipoleInduced dipole interactions permanent dipoles in groups such as CO can also induce a dipole moment in a neighboring group like CH3 by virtue of their ability to distort the distribution of its electronic cloud c Londondisoersion forces arise from the fact that the electronic cloud of nonpolar groups such as CH3 is not static but rather experiences rapidly fluctuating motions and in doing so generates a small transient dipole 11 Water a Highly polar due to charge separation or polarization of electronic clouds b Can act as Hbond donor or acceptor c Each water molecule interacts with four other water molecules d lce Hbonds are highly stablestatic expanded water with lower density 92gml e Liquid Hbonds are loose and disordered Unstable and dynamic f Universal solvent excellent solvent for hydrophilic substances those with polar or ionic character g Ability to dissolve polar substances its dipolar character enables it to weaken attractive forces between between oppositely charged ions NaCl h 12 Hydration solvation multiple water molecules surround each ion and neutralize its charge 13 Apolar molecules aggregate when in contact with water ex oils and lipids driven by entropy 14 Hvdroohobic effect driven by an entropic force because the ability of apolar substances to aggregate confers upon surrounding water molecules an entropic advantage exclusion of water molecules enables them water molecules to move and tumble freely increased entropy instead of being locked in an ordered manner with apolar neighbors a Apolar molecules introduced in water aggregate closely in order to minimize their surface area to prevent more water molecules to make more Hbonds with bulk water molecules which would decrease entropy unfavorable By aggregating water molecules can move more freely b Maintenance of intramolecular Hbonding network is crucial for the random motion and movement of water c Central to many biophysicochemical phenomena i separation of oil and water ii membrane bilayer integrity iii folding of proteins in water and lipid bilayer 15 Amphiphilic molecules molecules with hybrid character polar and apolar a Fatty Acids b Polar head interacts with water via Hbonding c Apolar tails exclude water on thermodynamic grounds d Aggregate in water but in an orderly manner driven by hydrophobic effect i Micelles monolayer ii Bicelles bilayer 16 Osmotic pressure pressure needed to prevent influx of water into the tube lower concentration region 17 Dialysis both solvent and solute molecules move or diffuse freely from regions of their respective high concentration to regions of low concentration across a permeable membrane until solute concentration reaches an equilibrium across both sides 12b Chemical Properties 1 HOH lt2 H OH 2 Hydronium ion H30 3 Proton lumping proton of hydronium molecule jumps from one H20 molecule to another a H and OH thus exhibit much higher mobilities in bulk water compared to other ions b Acidbase reactions exchange of H rank among the fastest processes occurring in water c H considered product of H20 dissociation instead of H30 4 Solutions a Neutral H 1OA7M b ACidiC H gt 1OA7 c Basic H lt 10quot7 5 pH logH a Blood 74 b Milk 7 c Vinegar 3 d Gastric Juice 15 6 Q equilibrium dissociation constant Molar Units a Ka HAHA b The greater the Ka stronger acid and weaker base c The greater the pKa weaker acid and stronger base 7 pKa strength of an acid in aqueous solution defined as the negative log of Ka a pKa logKa 8 HendersonHasselbalch equation pH pKa ogAHA a When HA A ogAHA O pH pKa b pH of solution is equivalent to pKa of an acid at 50 dissociation c Does not take into account dissociation of water so it s only useful for rationalizing the ionization of weak acidsbases such as i Buffers ii Amino acid sidechain groups in proteins 9 Buffer mixture of a weak acid HA and its conjugate base A HA c H A a Most effective when its H concentration and conjugate base A concentration are equal pH pKa b Maintain pH by binding to H or OH ions c ONLY resists small changes in pH in the region close to its pKa value plateau i pH pKa 1 10 Polvorotic Acids can lose more than one proton upon successive ionizations a Has multiple pKa values b EX phosphoric acid H3PO4 i pK1 22 ii pK2 68 iii pK3 122 Questions 1 Sketch a diagram of a water molecule and indicate the ends that bear a positive and negative charges 2 Compare the structures of ice and water with respect to the number and geometry of hydrogen bonds In ice each water molecule interacts tetrahedrally sp3 with four other neighboring water molecules Each hydrogen bond is static Ice density 092 gml In water water molecules rapidly uctuate and tumble on a picosecond timescale and is highly disordered Nethertheless water molecules transiently engage in rings of three 3mer four 4mer or five 5mer molecules in liquid Because of the irregularity water can pack much more tightly than ice and has a density of 100gml 3 Describe the nature and relative strength of covalent bonds ionic interactions and van der Waals forces Covalent bonds gt ionic bonds gt hydrogen bonds gt Dipole Dipole interaction gt LD forces Covalent bonds are the sharing of electrons between atoms ionic bonds are the interactions between oppositely charged ions van der Waals is an interaction between the dipoles of molecules Hydrogen bonding is a special case of dipoledipole interaction Van der Waals include hydrogen bonding dipole dipole interaction dipoleinduced dipole interaction and london dispersion forces 4 EXplain why polar substances dissolve in water while nonpolar substances do not What is the role of entropy in the hydrophobic effect Polar substances dissolve in water just like with ionic substances due to the interaction between the polar charges of water molecules and the attractive forces of other polar substances This phenomenon is known as hydration Nonpolar substances do not dissolve in water due to the hydrophobic effect which allows for an increase in the entropy of the system substances are separated from each other and not congregated The hydrophobic effect is largely driven by an entropic force in that the ability of apolar substances to aggregate confers upon surrounding water molecules an entropic advantage apolar substances can move about freely amongst each other if they are locked with water molecules they can not move about freely 5 EXplain why amphiphiles form micelles or bilayers in water Due to the hydrophobic effect the polar heads of the amphiphiles bind to water molecules while the apolar parts bond to each other 6 How does osmosis differ from diffusion Which process occurs during dialysis Osmosis only involves the movement of water from high to low concentration Diffusion is the movement of a molecule either water or a solute from high to low concentration Dialysis is the the moment of a solute from high to low concentration So diffusion occurs during dialysis 7 What are the products of ionization of water How are their concentrations related H and H30 OH39 8 Describe how to calculate pH from the concentration of H or 0H pHlogH or pOHlogOH 9 Define acid and base Acid is a chemical substance with a pH lt 7 Base is a chemical substance with a pH gt 7 10 What is the relationship between the strength of an acid and its pKa value H Ka HAA logH logKa logHAA pH pKa10g A JHAH gt Note that the pHpKa when A HA This is the point of 50 dissociation 11 What must a buffer solution include in order to resist changes in pH on addition of acid or base Since buffers resist changes in pH they are most effective when the concentration of its hydrogen ion H and conjugative base A are equaltherefore pHpKa i1 The addition of small amounts of H or 0H are quickly mopped up with little changes in solution pH 12 Why is it important to maintain biological molecules in a buffered solution Because minor deviations in the pH can cause biological molecules to dissociate and may lead to the death of the organism 13 Carbohydrates 13a Monosaccharide Stereochemistry Vocabulary 1 Monosaccharides carbonyl polyols polyhydroxy carbonyls contain a single carbonyl CO group bundled with multiple hydroxyl OH moieties a CH20subn where n gt 3 b Classified by whether the carbonyl is an i Aldehyde Aldoses ii Ketone Ketoses c Synthesized from smaller precursors that are ultimately derived from CO2 and H20 by photosynthesis d Complex stereochemical properties i Chiral molecules have an asymmetric C atom attached to four different substituent groups ii Enantiomers nonsuperimposable mirror image of the chiral molecule pair they have different stereochemical configurations at all chiral centers 1 rightdextrorotatory D in plane of polarized light 2 leftlevorotatory L in plane of polarized light iii Fischer Proiections employed to depict the DL configuration of chiral molecules 1 2D representation of 3D molecules 2 Horizontal lines bonds coming out of the page 3 Vertical lines bonds extending into the page iv Monosaccharides are assigned DL configurations on the basis of spatial position of the four substituents attached to the asymmetric O atom farthest away from the carbonyl group relative to olvceraldehvde 1 if OH is to the left Lisomer 2 if OH is to the right Disomer v Lsugars are RARE in nature Dprefix usually omittedimplied vi 2quotn stereoisomers 1 n number of asymmetric C atoms or chiral centers e Optical lsomers a class of stereoisomers that rotate the plane of polarized light due to at least one chiral center i Enantiomers differ in their configuration at all chiral centers hence are nonsuperimposable images of each other ii Diastereomers differ in their configuration at one or more but not all chiral centers 1 Epimers differ in the configuration at only ONE chiral center a Ex Glucose and Galactose differ in OH group C4 f Aldoses Aldehydebased monosaccharides Aldotriose Aldotetrose Aldopentose i Biologically most common DGlyceraldehyde Aldotriose DRibose Rib Aldopentose DGlucose Glc Aldohexose DMannose Man Aldohexose 5 DGalactose Gal Aldohexose g Ketoses Ketonebased monosaccharides i Biologically most common 1 Dihydroxyacetone Ketotriose 2 DRibulose Ketopentose 3 DFructose Ketohexose 2 Hemiacetal in the cyclic form the union between the carbonyl and hydroxyl group due to a nucleophilic attack of Hydroxyl O atom on Carbonyl C atom from ALDOSES 3 Hemiketal in the cyclic form the union between the carbonyl and hydroxyl group due to a nucleophilic attack of Hydroxyl O atom on Carbonyl C atom from KETOSES 4 Monosaccharides predominantly exist in cyclic forms 5 to 6 membered in both liquid and solid state thermodynamic equilibrium due to nucleophilic reaction 5 Gluc0pvranose 6 membered cyclic ring formed spontaneously from linear glucose due to nucleophilic reaction 6 Em 6membered cyclic forms of monosaccharides named in analogy with the heterocyclic pyran ring 7 Fructofuranose 5membered cyclic ring formed spontaneously from linear form of fructose due to nucleophilic reaction C2 in CO attacks H in hydroxyl group attached to C5 8 W 5membered cyclic forms of monosaccharides named in analogy with the heterocyclic furan ring 9 Haworth Proiection represents 3D stereochemical configurations of cyclic forms of monosaccharides a Heterocyclic ring lies perpendicular to the plane of the page PPONT b Wedged lines atoms coming toward the observer c Vertical lines atoms above or below the plane of the ring d Substituents below the plane right hand side of FischerProjection position of OH group involved in cyclization replaced with the lefthand side H atom e Heterocyclic ring nonplanar due to tetrahedral sp3 hybridization of atomic orbitals adopt chair conformation to minimize steric clashes i Bulkiest substituents compete with smaller groups for the less crowded equatorial positions rather than more crowded axial positions ii 2 chair conformations one in which bulkiest groups are in equatorial position is the thermodynamically most favorable 10 Anomers special class of epimers in that they are concerned with the stereochemical configuration only at the anomeric O atom hemiacetal or hemiketal group of cyclic sugar a Two anomers of the same linear monosaccharide have distinct physicochemical properties including ability to differentially rotate the plane of polarized light b NOT mirror images of each other so they are DIASTEREOMERS like epimers c alphaDglucopyranose and alphaLglucopyranose are ENANTIOMERS plot twist 11 Anomeric Carbon the carbonyl O atom that becomes chiral with two possible stereochemical configurations upon cyclization 12 Pairs of stereoisomers at the anomeric O atom freely interconvert thermodynamic equilibrium a Alpha anomer anomeric OH group orients below the plane of the ring on the side opposite to the CHZOH substituent attached to the hydroxyl O atom involved in cyclization b Beta anomer the anomeric OH group orients above the plane of the ring on the same side as the CHZOH substituent attached to the hydroxyl O atom involved in cyclization 13b Monosaccharide Derivatives Vocabulary 1 Derivatives other forms in which monosaccharides can exist 2 Aldonic Acids CHO gt COOH a Oxidation of the terminal CHO group of an aldose generates the corresponding polyhydroxy carboxylic acid derivative called Aldonic acid b Nomenclature replace the suffix ose in the aldose to m in the aldonic acid i Ex oxidation of CHO terminal group of glucose generates 9w 3 Alduronic Acids CHZOH gt COOH a Oxidation of the terminal CHZOH group of an aldose generates the corresponding polyhydroxycarbonyl carboxylic acid called Alduronic acid or Uronic m b Nomenclature replace the suffix ose in the aldose to uronic in the alduronic acid i Ex oxidation of CHZOH group of glucose generates Cilucuronic acid a component of glycosaminoglycans extracellular matrix Alditols CHO gt CHZOH a Reduction of the terminal CHO group of an aldose generates the corresponding sugar alcohol polyol called Alditol b Nomenclature replace the suffix ose in the aldose to ito in the alditol i Ex reduction of the terminal CHO group of glucose generates glucitol commonly known as sorbitol used as a sweetener Deoxy Sugars OH gt H a Reduction via reductases of an OH group to H generates the corresponding deoxy sugar b Nomenclature prefix the sugar with ndeoxy n position of OH reduced or replaced i Ex reduction of the OH group C2 of m generates deoxyribose a component of DNA Phospho Sugars OH gt OPO3quot2 a Phosphorylation via kinases of an OH group to phosphate moiety generates the corresponding phosoho suoar or sugar phosphate b Nomenclature suffixing the sugar with nphosphate n position of OH phosphorylated i Ex phosphorylation of the OH group C6 of glucose generates olucose6ph03phate key intermediate involved in the oxidation of glucose from food via glycolysis to produce energy ii alphaDglucopyranose c alphaDGlucopyranose6 phosphate glycolytic intermediate rings example W OH gt NH2 a Replacement or amination of an OH group with NH2 moiety generates the corresponding amino sugar b Nomenclature prefix the sugar with naminondeoxv n position of Oh replaced i Ex amination of the OH group C2 of glucose generates 2amino2deoxvalphaDolucoovranose alphaDolucosamine component of glycosaminoglycans extracellular matrix ii alphaDolucosamine Generic name iii 2amino2deoxvalphaDolucoovranose Systematic name W OH gt NH2 gt HNCOCH3 a Acetylation of amino sugars at the NH2 moiety so as to generate the corresponding acetyl sugar b Nomenclature prefix the sugar with nacetvlaminondeoxv n position of OH replaced i Ex acetylation of the NH2 group C2 of glucose generates 2acetvlamino2deoxvalphaDCilucorwranose NacetvlalphaDolucosamine a component of glycosaminoglycans extracellular matrix 9 OGlycosides OH gt OR a Condensation of anomeric O atom or hemiacetalketal group with OH group from another alcohol ROH which may or may not be another sugar i Results in formation of an Oolvcosidic bond between anomeric O atom and alcohol O atom product is called Oglycoside 1 extremely common in nature 2 serve as building blocks of disaccharides and more complex polysaccharides 10 NGlycosides OH gt NHR a Condensation of anomeric O atom of sugars with an M or M group from an amine ex RNH2 i Results in formation of an Nolvcosidic bond between anomeric O atom and amine N atom product is called Nglycoside 1 common in nature 2 serve as the building blocks of RNA and DNA in the form of deoxyribonucleotides 13c Polysaccharides Vocabulary 1 Polvsaccharides glycans comprised of two or more monosaccharides covalently linked together via olvcosidic bonds a Not only form linear polymers but also branched chains i Due to their polyhydroxy feature which enables them to engage in the formation of multiple Oglycosidic bonds on the same monosaccharide 2 Saccharides classified according to the number n of sugar units they have a Monosaccharide gt n1 b Disaccharide gt n2 c Oligosaccharide gt 3lt n lt 10 d Polysaccharide gt n gt 10 3 Homoglycans polysaccharides with identical sugar units 4 Heteroglycans polysaccharides with nonidentical sugar units or residues 5 lecoconiuoates polysaccharides that covalently associate with proteins and lipids to form complex macromolecules a Ex Glycoproteins proteoglycans glycolipids and lipopolysaccharides 6 Polysaccharide and glycoconjugate functions a structural support to various tissues through metabolism and cellular signaling b assisting the folding of proteins Lactose disaccharide a betaDLactose b betaDgalactopyranosyl1 gt 4betaDglucopyranose c formed via the beta1 gt beta4 glycosidic linkage between galactose and glucose d Bl gt B4 glycosidic linkage must be stated within the parentheses along with the position of linked A atoms and their anomericity or that of constituent sugars e It s the milk sugar and can make up as much as 10weightunit weight of milk f Lac latin for milk Sucrose disaccharide a betaDSucrose b alphaDglucopyranosyll gt 2betaDfructofuranose c formed via the al gt b2 glycosidic linkage between glucose aD glucopyranose and fructose bDfructofuranose fruit sugar d It s the table sugar extracted from sugarcane or sugarbeet Starch storage homoglycan a mixture of aamylose and amylopectin two closely related homoglycans comprised of thousands of repeating units of aDglucose b aamylose linear biopolymer in which repetitive glucose aD lucose units are joined together via a1 gt a4 glycosidic linkages in headtotail fashion c amylopectin linear chain of aamylose to which additional glucose units are added via the al gt a6 glycosidic linkages to generate a branched biooolvmer branch points every 30 residues or so 10 Glycogen storage homoglycan 11 a shares primary structure with amylopectin but it is more branched i a1 gt a6 glycosidic linkages occur every 10 glucose units on average b Principal fuel storage or energy reservoir in animals i deposited as insoluble granules largely in liver but also present in virtually all cells ii can compromise as much as 10ww of liver c Glycogenesis process where excess glucose produced via the hydrolysis of starch in meal is converted to glycogen in the body for storage d lecooenolvsis glycogen is converted quickly back to glucose to produce energy under times of starvation Cellulose structural homoglycan a linear biopolymer homoglycan made of thousands of BDGlucose units b formed via the repetitive Bl gt B4 ClIVCOSidiC linkages between consecutive glucose BDGlucopyranose units joined together in headtotail fashion c major structural component of the cell wall of plants i Wood as much as 50ww cellulose ii Cotton fiber as much as 90ww cellulose d Secreted by many bacteria in the form of biofilm e Most abundant oroanic biooolvmer on Earth 12 Chitin structural homoglycan a linear biopolymer homoglycan made up of repeating units of NacetylBD glucosamine derivative of glucose and closely related to cellulose b formed via repetitive Bl gt B4 glycosidic linkages between consecutive Nacetylglucosamine NacetvlBDolucosamine units joined together in headtotail fashion c Major structural component of exoskeletons of invertebrates such as crustaceans and insects also prominent component of cell walls of fungi and algae d Second most abundant oroanic biooolvmer on Earth 13 Hyaluronan complex heteroglycan a One of several closely related linear heteroglycans known as Givcosaminoolvcans comprised of a disaccharide repeating unit in which one of the two monosaccharides is an amino sugar usually either olucosamine or oalactosamine b AKA Hyaluronate and Hvaluronic acid c Disaccharide unit is provided by olucuronate olucuronic acid linked to amp acetvlolucosamine via the Bl gt B3 intraglycosidic linkage d Major component of extracellular matrix ECM between connective tissues such as cartilage and synovial fluid between joints helps to reduce friction as well as serve as lubricant and shock absorber 14 Heparin complex heteroglycan a Highly sulfated olvcosaminoolvcan b Disaccharide unit provided by Liduronate2sulfate uronic acid derivative of idose linked to Nsulfoolucosamine6sulfate via the al gt a4 intraqlvcosidic anage c Disaccharide units link together in headtotail manner via the al gt a4 interglycosidic linkage in their thousands to generate the hiohlv neoativelv charged hepann d NOT a major component of ECM between connective tissues e Primarily occurs in the intracellular granules of mast cells of arterial walls where it acts as an anticoagulant to prevent formation of runaway blood clots f Also clinically administered as an anticoagulant blood thinner in individuals with thrombotic disorders 15 Structural Homoglycans cellulose vs Storage Homoglycans starch a Are essentially stereoisomers of each other b exhibit distinct physicochemical properties c Structural homoglycans i adopt extended conformation ii allows them to tightly pack as stacked sheets forming 2D elongated fibers and thin filaments iii ideally suited to provide mechanical strength and structural support to surrounding tissues d Storage Homoglycans i largely assume irregular helical conformations ii allow them to loosely pack into coiledcoils helices wind around each other like a rope 1 quickly exposes them to enzymes for rapid metabolic breakdown Questions 1 How does an aldose differ from a ketose When looking at monosaccharides they are Classified on the basis of whether the carbonyl CO group is an aldehyde aldose or a ketone ketose 2 Draw 21 Fischer projection of Dglucose Draw two stereoisomers of this molecule including one that is an epimer 3 Show how aldoses and ketoses can form five and sixmembered rings 4 Draw a Haworth projection of Dglucose and identify it as an Ot or B anomer 5 Explain why anomers of a monosaccharide can readily interconvert whereas epimers do not Anomers of a monosaccharide can readily interconvert because monosaccharides exist both in linear and ring formation when they become ring formation depending on how the C5 asymmetric carbon attacks the anomeric carbon Cl from above or below will determine which anomer it is Epimers do not interconvert because the configuration itself of the hydroxyl groups on the asymmetric carbons are different thus they cannot move about and switch sides 6 Know the schemes that generate aldonic acids uronic acids alditols deoxy sugars and amino sugars aldonic acids formed from the oxidation of Cl COH carbon into COOH uronic acids formed from the oxidation of terminal CHZOH carbon into COOH alditols formed from the reduction of Cl COH carbon into CHZOH deoxy sugars formed from the reduction of one of the asymmetric carbons hydroxyl groups OH into a hydrogen H phospho sugars formed from the phosphorylation of an hydroxyl OH group into OPng amino sugar formed from the amination of a hydroxyl OH group into an amino NH2 group acetyl sugar formed from the acetylation of an amino NH2 group that was once the product of an amination of a hydroxyl OH group 7 Explain why a sugar can form at least 2 different glycosides A sugar can form at least 2 different glycosides depending on whether an alcohol ROH or an amine RNHZ The two different glycosides are Oglycosides and N glycosides Resulting bond is called an Oglycosidic or an N glycosidic bond 8 Describe the monosaccharide units and their linkages in the common disaccharides and polysaccharides Lactose Bl gt84 galactoseglucose Sucrose Cdgt82 glucosefructose Starch ozamylose glucose ozl gtoz4 glucose They are linear amylopectin glucose ozl gtoz6 glucose They are branched Branch points occurring every 30 residues or so Glycogen ozamylose glucose ozl gtoz4 glucose They are linear amylopectin glucose 01 gtoz6 glucose They are branched Branch points occurring every 10 residues or so Cellulose Bl gt84 glycosidic linkages between consecutive glucose units Chitin consecutive Bl gt84 NacetyIBDglucosamine linkages Hyaluronan Formed from intraglycosidic Bl gt83 DGlucuronate and NAcetyID Glucosamine disaccharide units linked together via an interglycosidic Bl gt84 anages Heparin Formed from intraglycosidic 01 gtoz4 Llduronate2sulfate and NSulfoD glucosamine6sulfate disaccharide units linked together via an interglycosidic 01 gtoz4 linkages 9 Explain why the systematic name of an oligosaccharide must include more than just the names of the component monosaccharides Because it must include how the glycosidic bonds are occurring between the monosaccharides 10 Compare and contrast the structures and functions of cellulose chitin starch and glycogen Cellulose and Chitin adopt an organize sheet like fashion that allows for high package Hence why they are protective structures Starch and glycogen adopt a helical like fashion that allows for increased surface areas so that enzymes can attack easily and they can be broken down quickly for energy usage Hence why they are energy storage 11 How do the physical properties of glycosaminoglycans and similar molecules relate to their biological roles Hyaluronan is a major component of extracellular matriX between connective tissues such as cartilage and synovial uid between joints where it helps to reduce friction as well as serve as a lubricant and shock absorber Heparin primarily occurs in the intracellular granules of mast cells of arterial walls where it acts as an anti coagulant to prevent the formation of runaway blood clots Also administered as an anticoagulant blood thinner in individuals with thrombotic disorders 14 Lipids 14a Lipid Classification Vocabulary 1 Lipids hydrophobic molecules that usually harbor some degree of amphiphilic character polar and apolar regions a DO NOT polymerize b Different functions have lipid bilayer energy reservoirs regulate chemical messengers steroid hormones c 5 major categories 2 Fatty acids carboxylic acids with long aliphatic tail a saturated lack CC bonds i have greater conformational flexibility b unsaturated have one or more CC bonds i exist as cistrans stereoisomers cis is thermodynamically more stable ii can adopt 2 cistrans stereoisomers n is of CC bonds c Assigned XM symbol i X the of C atoms ii M the of double bonds d Melting Point increases with increasing X carbons decreases with increasing M CC bonds e Common FAs i Stearic acid Octadecanoic acid Saturated ii Oleic acid 9Octadecanoic acid Unsaturated 3 Triglycerides Fatty acid esters of glvcerol a formed via the esterification RCOOH of the carboxylic group of FA with the hydroxyl group of glycerol b AKA triacvlglvcerols usually with different fatty acid R groups c major constituent of cooking oils and fats d oil vs fat liquid vs solid room temperature i oils unsaturated FA ii fats saturated FA e function as high energy reservoirs in adipose tissue f less oxidized than carbs and proteins so they yield more energy per unit mass upon oxidative metabolism g Common Triglycerides i Caster Oil triricinolein ii Vernonia Oil trivernolin 4 Phosoholipids CllvcerODhOSDholipids Fatty acid esters of phosphoglycerol glycerol3 phosphate a 2 of the 3 C atom groups are esterified to FA R groups C1 and C2 b C3 atom is derivatized with another functional group called X usually polar c Highly amphiphilic partially hydrophobic fatty acid tails partially hydrophilic phospho moiety d serve as major components of biological membranes e Common Phospholipids i Phosphatidic acid ii Phosphatidylcholine lecithin bent iii Phosphatidylglycerol 5 Sphingolipids Derivatives of ceramides a Ceramides fatty acid amides of sphingosine an amino alcohol fatty acid group R is amidated onto NH3 group amidation RCOOH b Sphingolipid functional group is conjugated either via a phosphoester or ether linkage to one of the OH groups c major component of biological membranes key role in signal transduction and molecular recognition particularly around brain and CNS d 3 major classes depending on the nature of moiety X i Sphingomyelins phosphocholine or phosphoethanolamine moiety 1 Phosphocholine head group X 2 Palmitate residue ii Cerebrosides monosaccharide moiety iii Gangliosides oligosaccharide moiety 1 Sugars with sialic acid attached N acetylneuraminidate 2 Stearic Acid residue C2 with NH3 6 Steroidolipids steroids derivatives of cyclopentanoperhydrophenanthrene sterane a Sterane 17carbon polycyclic aromatic hydrocarbon comprised of four nonplanar rings AD fused together b Cholesterol most abundant sterane in animals i 3rd major component of biological membranes 3040 molmol of total membrane lipids ii greater rigidity than phospholipids and sphingolipids fused rings provides structural integrity and dynamic fluidity iii can be esterified to make cholestervl FAs iv metabolic precursor of steroid hormones c Steroid Hormones regulate variety of physiological functions central to cellular homeostasis chemical messengers i diffuse through the cell membrane and bind to steroid hormone receptors SH Rs intracellular cytoplasmic and nuclear receptors ii Highly hydrophobic iii 5 major classes 1 Glucocorticoids Metabolism and inflammation a ex cortisol adrenal glands 2 Mineralocorticoids Osmoregulation a Aldosterone adrenal glands 3 Androgens Male sex development a Testosterone 4 Estrogens Female sex development a Estradiol 5 Progesterones Menstruation pregnancy 14b Biological Membranes Vocabulary 1 Detergent micelles monolayers singletailed detergents amphiphilic like FAs and SDS aggregate into higherorder structures called micelles a nonpolar tails avoid contact with water while polar tails interact with the solvent b formation of micelles is driven by thermodynamic favorability Van der Waals interaction between tails c Diameter dependent on length of tail d Central cavity may be filled with water depending on concentration of detergent molecules 2 Lipid Bicelles bilayers doubletailed amphiphilic molecules like phospholipids aggregate into disclike structures called bicelles a steric clashes between lipids require the formation of the disclike structure b Hydrophobic effect ability to exclude water from their nonpolar surfaces i also the basis of folding of proteins into 3D shapes 3 Liposomes bilayers 3D spherical structures fully enclosed by a single lipid bilayer with a central aqueous cavity a formed from phospholipid bicelles when disrupted b serve as artificial membranes vehicle for the delivery of hydrophilic nutrients and drugs through cell membranes i hydrophobic nutrients and drugs dissolve into lipid bilayer of liposomes c fuse with biological membranes 4 Lipid bilayer fluidity a Lateral diffusion rapid process allows biological membranes to be dynamic and fluid structures b Transverse diffusion flipflop very slow is rare due to it thermodynamic constraints c Lipid tails are constantly in motion due to free rotation about the 00 bond d described as a 2D fluid thanks to the mobility of lipids e fluidity of bilayer is dependent upon temperature and lipid composition f lipid bilayer undergoes a phase transition from highly viscous liquid solution to a gellike solid liquid crystal i Transition temperature Tm temperature at which the bilayer melts ii Tm is highly dependent on chain length x and degree of saturation m 1 longer chain or higher degree higher temperature g changing composition of FAs in membrane lipids can attune the Tm of lipid bHayer h cholesterol serves as fluidity buffer broadens or completely abolishes phase transition i TgtTm Liquid solution cholesterol decreases fluidity ii TltTm Gellike solid with an ordered array cholesterol increases fluidity 5 Membrane Proteins Integral and Peripheral a lMPs traverse through lipid bilayer once monotopic or multiple times polytopic hydrophobic and insoluble in water b PMPs adhere to either inner or outer leaflet of bilayer 6 Integral Membrane Proteins IMP a amphiphiles nonpolar amino acid residues inside polar and charged residues outside b transmembrane segments adopt two major folds ahelical or 8 barrel c Bbarrel transmembrane proteins allow passive diffusion of nutrients salt and water thanks to its closed hollow channel d ahelical transmembrane proteins can be monotopic and polytopic to form a helical bundle conduct from signal transduction to energy generation 7 Peripheral Membrane Proteins PMP a adhere to surface of either inner or outer leaflet of the bilayer b watersoluble proteins impart structural and functional versatility upon biological molecules i can serve as membrane skeleton and as a framework for the integration and operation of signaling networks 8 Fluid Mosaic Model a lipid bilayer can be described as a fluid mosaic heterogeneous mixture made up of lipids proteins and such arranged in an orderly manner b lMPs undergo similar lateral diffusion 9 Asymmetric distribution of lipids a protein components of biological membranes are not evenly distributed on both sides b lipids are asymmetrically distributed on each face of the lipid bilayer c asymmetric distribution is necessary to attune specific cell types Questions 1 How do lipids differ from the three other major classes of biological molecules Lipids do not polymerize they have both polar and nonpolar regions they serve as gatekeepers lipid bilayers energy reservoirs and Chemical messengers They have roughly double the amount of stored energy compared to carbohydrates and proteins due to being less oxidized 2 Explain the trend in melting point with increasing fatty acid chain length and number of double bonds xm Where X represents the number of carbon atoms and m represents the number of CC double bonds An increase in the the number of carbon atoms xincreasing fatty acid chain length leads to an increase in melting point However an increase in the number of double bonds leads to a decrease in the melting point 3 Summarize the structures and physical properties of fatty acids triglycerides phospholipids sphingolipids and steroids Fatty acids carboxylic acids with long aliphatic tails Triglycerides glycerol derivatives of fatty acids Phospholipids phosphoglycerol derivatives of fatty acids Sphingolipids derivatives of ceramides Steroidolipids steroids derivatives of sterane OOOOO gt Revert to notes above more detail 4 Summarize the functions of steroid hormones Highly hydrophobic can diffuse through the cell membrane and bind to specific intracellular receptors called steroid hormone receptors SHRs Five Major Classes 0 Glucocorticoids eg Cortisol made in adrenal glands Metabolismin ammation O Mineralocorticoids eg Aldosterone made in adrenal glands Osmoregulation O Androgens eg Testosterone made in testes Male sexual development 0 Estrogens eg Estradiol made in ovaries Female sexual development 0 Progesterones eg Progesterone made in ovaries Menstruation 5 Why do glycerophospholipids and sphingolipidsbut not fatty acidsform bilayers Sphingolipids and glycerophospholipids form bilayers because they have both polar and apolar parts causing them to aggregate and form layers Due to the hydrophobic effect Fatty acids do not have both polar and apolar parts They are only composed of apolar therefore they do not aggregate and form layers 6 Explain why lateral diffusion of membrane lipids is faster than transverse diffusion Lateral diffusion lipid exchange that happens very rapidly in membrane Transverse diffusion ip op lipid exchange that happens very slowly in membrane since polar head must be in an apolar environment prior to regressing back to polar environment 7 What factors in uence the uidity of a bilayer Transition temperature Tm temperature in which the lipid bilayer undergoes a dramatic phase transition in vitro from liquid solution to a gel like solid liquid crystal Usually around 25 OC Tmis dependent upon Xm and Cholesterol which acts as a buffer for Tm When T gt Tm cholesterol decreases uidity When T lt Tm cholesterol increases uidity 8 What are the two types of secondary structures that occur in transmembrane proteins Integral membrane proteins IMPs transverse through the lipid bilayer once monotropic or multiple times polytopic They are highly hydrophobic and insoluble They are essentially amphiphiles OtIMPs helical conduct roles involving signal transduction and energy generation BIMPs barrel are sheet like and form a barrel shape allowing passive diffusion of nutrients salts and water Peripheral membrane proteins PMPs adhere to the surface of either inner or outer lea et of the bilayer via association with lipid head groups or nontransmembrane regions of IMPs PMPs are water soluble eg spectrin actin and ankyrin serve as membrane skeleton giving cells shape and framework for the smooth integration and operation of signaling networks running from the nucleus to the events on cell surface 15 Membrane Transport 15a Passive Transport Vocabulary 1 Mechanism a passive transoort the movement of molecules along a chemical potential gradient across biological membranes from region of high concentration to region of low concentration b only apolar substances can diffuse through biological membranes i steroid hormone gas 02 and C02 fatsoluble vitamins c small polar molecules water can diffuse but at a slower rate d rate of diffusion proportional to the concentration difference across the membrane and its solubility in the apolar core e filtration and osmosis are other examples of passive transport 2 Thermodynamics a chemical potential describes the amount of potential energy stored in the substance that can be used to do useful work Paaswe Tranapolrthhermndynamms r Cenaider the passive diffuaicn eff an alcclaur auhatance A frdrn extracellular eat aide td cytciplaaimic cw aide acrdaa a hidicgicaii rnerri bra ne J5let 393 Acct The chemical patential u liar partial melar free energy if anltite en each aide ia given by that RTlnlelai 1 Hm RTIinrieim 2 where um Chemical pretental df adiuite a an the extracellular aide calfmcl i um Cherncal pdtential df aciute a an the cttlplalamic aide icafmdll H Universal rndlar aa ccnatant 11919 calfmclfft T Aladlute tern peratume iii a Chemical pctehtal full is a ihtaical pli39UpIEFW at a substance related 39th ita cdncentraticn in a manner akin td ita telu me and dienaity that diescribes the arndunt cf pctential enery atcnred T the aubatance that can be uaed td did uaeful work The ipdtehtiall energyr atdredi in adlute a is thua clearlyquotr pmhdrticnal the difference in ita coincehtratidh acr daa the mern tarane aifir unitr petal such ccncentrat icn difference generatea a chemical pctential difference dull acreaa the mernhrane given by u hm pm gt RTlniAth v HiflnLelEM HTln eJm Aim 3 If lm a Aim 2 a l a Net flew dfi l tc cytcniplaarnic aide If elm rllji tim 22 i a Zero net flew cf A acrcaa the membrane If Aim e alth 3 gtiu 9 Net flew dfi i td extracellular aide 15b Facilitated Transport 1 Mechanisms a involves movement of polar and charged molecules along a membrane via micromolecular compounds or macromolecular proteins that serve as transmembrane hydrophilic vehicles b 3 major classes i Carriers travel across membrane and deliver a substance from one side to the other and return empty ionophore carriers 1 ionophore amphiphilic micromolecular compounds 2 carriers wrap around a specific ion via polar groups and aid in diffusion 3 after releasing the ion the carrier comes back to repeat the process 4 Valinomycin macrocyclic dodeca depsipeptide antibiotic that accommodates a single K ion and transports it 5 Depsipeptide peptide that harbors a mixture of amide and ester bonds ii Channels form tunnels to allow unhindered traffic of substance ion channels porin channels 1 ionoohore channels a amphiphilic micromolecular compounds b drill a tunnel through the membrane to increase permeability to specific ions flow results in discharge of electrochemical potential gradient c Gramicidin A linear pentadecapeptide antibiotic that folds into a headtohead helical dimer within lipid bilayers 2 ion channels a membrane potential excess Na ions outside the cell excess K ions inside the cell b discharge depolarization of the membrane potential is necessary to energize cellular processes such as signal transduction and neurotransmission c proteinequivalents of ionophore channels d KcsA bacterial ion channel that forms an ahelical conelike tunnel to facilitate the flow K ion out the cell tetramer e not constitutively open only open and closed when needed 3 porin channels a Bbarrels that drill hydrophilic tunnels through outer membrane of bacteria to allow diffusion of polar and charged molecules in a nonselective manner b act as molecular sieves c OmpF filters out larger molecules and allows passage to smaller ones d Maltoporin some porins act as channels in a highly selective manner maltodextrin oligosaccharide 4 aouaporin channels a ahelical bundles that form hollow channels through certain membranes to accelerate the flow of water in and out of the cell b AQP1 expressed in kidney cells and serves as a water channel in the form of a tetramer each bundle associates with 3 other subunits to form 4 adjacent membrane pores iii Transporters act as allostericallygated tunnels that open to allow passage in or to allow passage out glucose transporters 1 Glucose transporters facilitate cells uptake of glucose a glucose is a vital source of energy via respiration b GLUT1 12transmembrane a helical protein that forms an allostericallygated tunnel i bolsters a rather broad substrate specificity serves as a transporter for a number of aldoses glucose obvs and Vitamin C c binding of glucose to GLUT1 extracellular induces conformational change d transports other aldoses pentoses and hexoses and vitamin C 15c Active Transport 1 Features a Active transport can be described as i Uniport transport of 1 molecule in either direction predominant feature of facilitated transport ii Symport transport of 2 or more molecules in the same direction iii Antiport transport of 2 or more molecules in different dkec ons b Two classes i Primarv bumps energy from ATP hydrolysis ii Secondarv bumps energy from discharge of electrochemical ion gradients 2 Primarv bumps NaK Antiporter L Func on 1 Eukaryotic cells usually maintain ionic gradients across their plasma membranes thereby creating an electric voltage membrane potential 2 NaK antiporter is an ATPdriven pump that transports Na and K ions against their concentration gradients 3 electrochemical gradient generated plays a key role in the maintenance of cell volume as well as in restoring membrane potential ii Mechanism 1 antiporter switches between 2 conformations per transport cycle a ATPbound conformation E1 that recognizes Na ions on the cytoplasmic side b Phosphorylated conformation E2 that recognizes K ions on the extracellular side 3 Primarv pumps Ca2 Antiporter a Func on i influx of Ca ions is necessary for muscle contraction release of neurotransmitters and glycogen breakdown ii accordingly eukaryotic cells maintain an excess of Ca ions 1 mM outside the cell iii antiporter is an ATPdriven pump transports Cato extracellular side while transporting H ions to the cytoplasmic side b Mechanism i switches between 2 conformations per transport cycle 1 ATPbound conformation E1 that only recognizes Ca ions on the cytoplasmic side 2 Phosphorylated conformation E2 that only recognizes H ions on the extracellular side 4 Secondarv pumps NaGlu Svmporter a Intestinal epithelial cells lining the villi take up dietary glucose Glu via the NaGlu symporter i aka sodiumglucoselinked transporter SGLT b energy stored in the Na ion gradient across the membrane is coupled to the NaGlu symporter c energy derived from the dischargedissipation of downhill Na ion gradient is utilized by the NaGlu symporter to transport glucose against an uphill glucose gradient i plasma membrane NaGlu stoichiometry 21 SGLT1 or 11 SGLT2 Questions 1 What are the three forms of passive transport Passive diffusion filtration and osmosis 2 Define chemical potential of a substance How is it related to its concentration physical property of a substance related to its concentration The amount of potential energy stored in the substance that be used as work 3 How can you predict whether it will be thermodynamically favorable for an apolar substance to move from one side of a membrane to the other Dependent upon the concentration of the substance in both sides you can predict how it will ow based on the chemical potential difference formula 4 Provide examples of substances that can readily diffuse across a biological membrane Steroid hormones lipid based vitamins NDEK and gases 5 What are the three major classes of facilitated transport 0 Carriers carriages that travel across the membrane so as to shuttle a substance from one side to the other and then return unloaded eg ionophore carriers 0 Channels form tunnels or pores to allow unhindered traffic of a substance eg ionophore channels ion channels porin channels and aquaporin channels 0 Transporters act as allosterically gated tunnels that transiently open on the other side to allow its eXit eg glucose transporters 6 What are similarities and differences between ionophore channels and ion channels Ionophore ChannelsGramicidin A a literal drilled hole through the membrane as to increase the permeability to specific ions Gramicidin A is a linear pentadecapeptide antibiotic that folds into a head to head helical dimer within lipid bilayers the central lumen of this helical dimer is suitable for cations such as Na and K Ion channelsKcsA protein equivalent of ionophore channels KcsA is a bacterial ion channel that forms an Othelical cone like tunnel from 4 subunits into a tetramer to facilitate the ow of K ions Ion channels open and close as needed dependent on stimuli 7 Outline the mechanism of action of GLUTl transporter Glucose enters GLUTl allowing for a conformational change while inside GLUTl GLUTl changes conformation allowing for an opening in the other side of the membrane while the the side where glucose came from is closed off Glucose is released and conformational change back to the original position GLUTl is a 12membrane 0t helical protein 8 Distinguish between passive transport facilitated transport and active transport across biological membranes Passive transport uses no energy and involves hydrophobic molecules such as steroid hormones lipid based vitamins ADEK and gases Facilitated transport uses no energy involves the transport of hydrophilic molecules by usage of a carrier Valinomycin channel Gramicidin A KcsA OmpF AQPl or transporter GLUl Active transport uses energy Involves either a primary or secondary pump 9 What are the two forms of active transport What is the direct and ultimate source of energy for each form Primary pump Na K Antiporter or Ca AntiporterUses ATP directily Secondary pump NaGlu Symporter uses ATP indirectly 10 EXplain why the Na K antiporter and the Ca antiporter carry out unidirectional transport with respect to each ion across the plasma membrane This question is vague and confusing Each ion only travels in one direction across its gradient 16 Biochemical Signaling 16a Endocrine Hormones 1 Hormones chemical messengers that play key role in cellular signaling exclusively produced by endocrine glands and travel in the blood to act at distant sites systematic action 2 Growth factors and Cytokines produced throughout body by numerous cell types and can act both locally and systemically 3 Endocrine System a Endocrine Glands i Glands organs in the body that synthesize and secrete chemical products such as sweat and insulin ii 2 categories of glands 1 m secrete their products via ducts to specific internal or external sites a Ex sweat glands salivary glands mammary glands 2 m secrete their products directly into the bloodstream a Ex pituitary thyroid and adrenal glands iii Not all glands are monolithic 1 Ex pancreas acts as both an endocrine and exocrine gland a islets of Langerhans 2 as an endocrine gland secretes insulin and glucagon b M is an exocrine gland secretes digestive enzymes such as trypsin and chymotrypsin to the small intestine b Endocrine Sionalino i In response to stimuli endocrine glands secrete hormones directly into the bloodstream so they can be carried to the target cells ii endocrine hormones elicit specific biological effects such as the maintenance of homeostasis upon arrival at the target site c Micromolecular Hormones i Hormones that regulate functions central to cellular homeostasis steroids 1 steroid hormones highly hydrophobiclipophilic exert their effects by being able to diffuse through the membrane and by binding to specific receptors called steroid hormone receptors SH Rs a subfamily of a nuclear receptor superfamily d Macromolecular Hormones i such as M and gm regulate blood sugar level ii insulin aids in the absorption of glucose from the bloodstream by muscle and adipose cells inhibits production of glucose by the liver 1 exerts such effects by binding and activating cell surface insulin receptors member of receptor tyrosine kinase RTKs family iii glucagon does the opposite of insulin it stimulates the liver to release glucose through the breakdown of glycogen glycogenolysis and the synthesis of glucose from noncarbohydrate precursors such as pyruvate and lactate gluconeogenesis 1 binds and activates the cell surface glucagon receptor member of the G proteincoupled receptor GPCR family iv insulin and glucagon act antagonistically to maintain a relatively constant blood glucose level 16b 3 Hormone Receptors 1 Steroid Hormone Receptors SHR a Structural Organization i SH Rs are watersoluble intracellular cytoplasmic and nuclear proteins that act as ligandmodulated transcription factors require a hormone for activation ii generally comprised of the TADBLB modular architecture 1 DNAbinding domain DB binds to promoters of target genes in a sequencedependent manner 2 Ligandbinding domain LB Recruits other cellular proteins such as transcription factors coactivators and co repressors to gene promoters in a liganddependent manner 3 Transactivation domain TA Synergizes the action of LB domain by recruiting additional cellular proteins required for the assembly of fully functional transcriptional machinery at the target gene promoters a Acts in a ligandindependent manner b A typical signaling cascade i SHRs exist as monomers in complex with heat shock proteins HSPs in cytoplasm ii steroid hormone binding to the LB domain results in m iii Dimeric SHR translocates to the nucleus and binds to the target gene promoters via its DB domain 1 Turns on gene expression of specific proteins gt set about causing changes to the cell in response to the hormone 2 Receptor Tvrosine Kinases RTK a Structural Organization i Singletransmembrane cell surface receptors comprised of 1 Extracellular ligand binding LB domain 2 Single ahelical transmembrane TM domain 3 Cytoplasmic tyrosine kinase TK domain ii Binding of a cognate ligand hormone cytokine or growth factor to extracellular LB domain iii Receptors either dimerize or undergo conformational change gt brings their cytoplasmic TK domains close together gt allows each TK domain to phosphorylate its dimeric counterpart specific Tyr residue in a transfashion each TK phosphorylates the other iv Autophosphorylation of RTKs results in activation gt they recruit specific signaling proteins to the site of inner membrane surface v Sets off cascade of downstream events ultimately culminating in nucleus b Autophosphorylation i Occurs one of the hydroxy amino acids Tyr Thr Ser PostTranslational modification PTM 1 molecular switch protein kinases and phosphatases work in tandem to maintain homeostasis tightly regulated in highly spatial and temporal manner c RTKs Insulin Receptor i IR binds insulin and insulinlike growth factors such as IGF1 and IGF2 1 exists in a disulfidelinked dimeric state even in the unbound conformation 2 involved in the regulation of glucose homeostasis d Typical Signaling Cascade i Ligand binding to RKT induces receptor dimerization andor autophosphorylation ii Activated receptor serves as binding site for recruitment of adaptors such as w via SH2 domain to the inner membrane surface IMS in a phosphorylationTyrdependent manner LB iii GRB2 exists in complex with SOS exchange factor the recruitment of SOS to IMS catalyzes GDPGTP exchange in Ras gt activation of Ras iv Ras binds and activates the kinase MEK via SerT hr phosohorvlation gt activation of the MAP kinases MAPKs ERK2 by MEK also via phosphorylation v Activated MAPK translocates to the nucleus and phosphorylates specific transcription factors ex JunFosMyc vi Phosphorylated Jun binds to its promoter within target genes and turn on gene of specific proteins Cell response to ligand BOOM BITCH 3 GProtein Couoled Receptors GPCRs a Structural Organization i Seventransmembrane cell surface receptors ii Transduce hormone signals and also ligandsstimuli as diverse as light odors iii Absence of ligand cytoplasmic tail of GPCRs binds to the GDPbound asubunit of the so called Gproteins membraneanchored heterotrimers of a b and y subunits gt union between GPCRs and Gproteins locks b and y subunits in an inactive state iv Upon ligand binding at extracellular face GPCRs undergo conformational change that result in GDTGTP exchange within the asubunit gt allows it asubunit to dissociate off both the GPCR cytoplasmic tail and its heterotrimeric partners b and y subunits 1 Allows both GTPbound asubunit and the bvheterodimer to act as modulators of other membranebound proteins such as a Adenylate cyclase AC b Phospholipase C PLC b Adenvlate Cvclase AC i AC catalyzes the conversion of ATP to cAMP ii cAMP acts as an intracellular secondary messenger in the cytosol gt targets and modulates the activities of other cellular proteins such as protein kinase A PKA regulation of carbs and lipid metabolism through phosphorylation c Phosoholipase C PLC i PLC catalyzes the hydrolysis of PP2 membrane phospholipid at its glycerophosphoester bond into P3 and DAG ii P3 and DAG gt act as intracellular secondary messengers in cytosol iii P3 triggers the opening of Caquot2 channels in the endoplasmic reticulum gt sudden increase of Ca and DAG activates protein kinase C PKC modulates numerous signaling cascades through phosphorylstion Questions 1 Explain why only certain cells respond to hormones even though all cells in the body are exposed to the hormone It is dependent if the cell has the receptors of the hormone Such as Steroid Hormone Receptors Cell Surface Insulin Receptor RTK family or Cell Surface Glucagon Receptor GPCR family 2 List hormones produced by the pancreas and adrenal glands What types of molecules are these hormones Pancreas produces macromolecules through the islet of Langerhans both insulin and glucagon which are peptidesproteins The pancreas also produced trypsin and chymotrypsin Adrenal Glands produce micromolecules such as glucocorticoids cortisol and mineralocorticoids aldosterone They are both steroids 3 Summarize the biological effects of insulin and glucagon Insulin secreted by pancreas the endocrine function of pancreas islets of Langerhans Aids in glucose uptake by cells from the bloodstream Inhibits production of glucose by liver Binds to cell surface insulin receptor a member of the receptor tyrosine kinase RTK family Glucagon secreted by pancreas the endocrine function of pancreas islets of Langerhans Stimulates the liver to release glucose through breakdown of glycogen and the synthesis of glucose from noncarbohydrate precursors such as pyruvate and lactate Gluconeogenesis Binds to the cell surface glucagon receptor a member of the Gproteincoupled receptor GPCR family 4 Summarize the biological effects of steroid hormones Steroid Hormone Receptors SHRs a subfamily of nuclear receptor superfamily a group of transcription factors that become activated upon binding of a ligand such as a hormone or vitamin causing an effect in the cell 5 How does a receptor tyrosine phosphorylate itself When the ligand binds to the LB domain a conformational change causes the TK domain to dimerize and thereby leading to phosphorylation by self 6 Summarize various members of RTK family their ligands and functions NO 7 Summarize the roles of proteins such as Grb2 SOS Ras and various protein kinases involved in coupling activated RTKs to downstream cellular targets such as transcription factors in the nucleus Receptor tyrosine kinases RTKs Insulin Remember they are one of the two subfamilies of the larger protein tyrosine kinase PTK the other being non receptor tyrosine kinases nRTKs LB domain Single 0thelical transmembrane TM domain Cytoplasmic tyrosine kinase TK domain When ligand binds dimerization occurs bringing proximity between individual LB domain Single 0thelical transmembrane TM domain Cytoplasmic tyrosine kinase TK domains The TK domains now proximate to each other then phosphorylate in a transfashion Results in activation causing signaling proteins to the site and setting off a cascade The cascade caused by adaptors such as GRB2 to the inner membrane surface IMS GRB2 exist in complex with SOS exchange factor the recruitment of SOS to the IMS catalyzes GDPGTP Activated Ras binds and activates Raf kinase Ref kinase activates the kinase MEK via phosphorylation In turn this activates MAPK MAPK enters the nucleus and phosphorylates specific transcription factors such as JunFosMyc Phosphorylated Jun binds to its promoter within the target genes and turns on gene expression specific proteins Insulin Receptor IR binds insulin and insulin like growth factors such as IGFl and IGF2 This is the LB domaingt lt 8 Explain why cells contain an array of protein phosphatases as well as protein kinases In order to activate and deactivate multiple proteins across the cell and cell membrane 9 Summarize the steps of signal transduction from a GPCR to phosphorylation of target proteins by PKA Gproteincoupled receptors GPCRs Glucagon They are seven transmembrane cell surface receptors called GPCR In absence of ligand the tail of the transmembrane cell surface receptor binds to GDPbound Otsubunit called Gproteins G proteins are membrane anchored heterotrimers of or B and subunits This locks the GPCR and Gproteins When a ligand activates GPCR GPCRs undergo a conformational change that results in GDPGTP exchange within the OL subunitThereby allowing it to dissociate off both the GPCR tail and its B and subunitss Such dissociation enables both the GTPbound Xsubunit and the 15 heterodimer to act as modulators of other membrane bound proteins such as adenylate cyclase AC and phospholipase C PLC Upon activation by the GTPboundOt subunit of Gproteins AC catalyzes the conversion of ATP to cAMP cAMP then acts as a secondary messenger in the cytosol in response to GPCRs cAMP targets and modulates the activities of other cellular proteins such as protein kinase A PKA involved in the regulation of carbohydrate and lipid metabolism by virtue of its ability to phosphorylate SerThr residues in target proteins Upon activation by the GTPboundOt subunit of Gproteins PLC catalyzes the hydrolysis of PIP2 a membrane phospholipid at its glycerophosphoester bond into 1P3 and DAG 1P3 and DAG then act as intracellular secondary messengers in the cytosol in responds to GPCRs 1P3 triggers the opening of Ca2 channels in the endoplasmic reticulum Sudden ood of calcium and DAG causes protein kinase C PKC to regulate gene eXpression by its method of phosphorylating SerThr residues in target proteins 10 What is the function of a secondary messenger such as cAMP To regulate carbohydrate regulation CAMP lipid regulation cAMP or gene eXpression DAG and Ca2 by its method of phosphorylating SerThr residues in target proteins
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