Human Anatomy and Physiology I
Human Anatomy and Physiology I BIOL 1151
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Date Created: 10/05/15
Chapter 25 Metabolism Ob39ectives Role of ATP in anabolism and catabolism Oxidationreduction reactions Carbohydrate metabolism Lipid metabolism Protein metabolism Heat and energy balance Nutrition guidelines minerals and vitamins Metabolism Functions of food source of energy essential nutrients stored for future use Metabolism is all the chemical reactions ofthe body some reactions produce the energy stored in ATP that other reactions consume all molecules will eventually be broken down and recycled or excreted from the body Catabolism and Anabolism Catabolic reactions breakdown complex organic compounds providing energy exergonic glycolysis Krebs cycle and electron transport Anabolic reactions synthesize complex molecules from small molecules requiring energy endergonic Exchange of energy requires use of ATP adenosine triphosphate molecule ATP Molecule amp Energy Each cell has about 1 billion ATP molecules that last for less than one minute Over half of the energy released from ATP is converted to heat Energy Transfer Energy is found in the bonds between atoms Oxidation is a decrease in the energy content of a molecule Reduction is the increase in the energy content ofa molecule Oxidationreduction reactions are always coupled within the body whenever a substance is oxidized another is almost simultaneously reduced Oxidation and Reduction Biological oxidation involves the loss of electrons hydrogen atoms dehydrogenation reactions require coenzymes to transfer hydrogen atoms to another compound common coenzymes of living cells that carry H NAD nicotinamide adenine dinucleotide NADP nicotinamide adenine dinucleotide phosphate FAD avin adenine dinucleotide Biological reduction is the addition of electrons hydrogen atoms to a molecule increase in potential energy ofthe molecule Mechanisms of ATP Generation Phosphorylation is bond attaching 3rd phosphate group contains stored energy Mechanisms of phosphorylation within animals substratelevel phosphorylation in cytosol oxidative phosphorylation in mitochondria in chlorophyllcontaining plants or bacteria photophosphorylation Phosphorylation in Animal Cells ln cytoplasm 1 ln mitochondria 2 3 amp 4 Carbohydrate Metabolismln Review 0 ln GI tract polysaccharides broken down into simple sugars absorption of simple sugars glucose fructose amp galactose 0 ln liver fructose amp galactose transformed into glucose storage of glycogen also in muscle 0 ln body cells functions of glucose oxidized to produce energy conversion into something else storage energy as triglyceride in fat Fate of Glucose ATP production during cell respiration uses glucose preferentially Converted to one of several amino acids in many different cells throughout the body Glycogenesis hundreds of glucose molecules combined to form glycogen for storage in liver amp skeletal muscles Lipogenesis triglyceride synthesis converted to glycerol amp fatty acids within liver amp sent to fat cells Glucose Movement into Cells In GI tract and kidney tubules Naglucose symporters Most other cells GluT facilitated diffusion transporters move glucose into cells 7 insulin increases number of GluT transporters in the membrane of most cells 7 in liver amp brain always lots of GluT transporters Glucose 6 phosphate forms immediately inside cell requires ATP thus glucose hidden in cell Concentration gradient favorable for more glucose to enter Glucose Catabolism 39 Cellular respiration 4 steps are involved glucose 02 produces H20 energy C02 39 Anaerobic respiration called glycolysis 1 formation of acetyl CoA 2 is transitional step to Krebs cycle 39 Aerobic respiration Krebs cycle 3 and electron transport chain 4 Glycolysis of Glucose amp Fate of Pyruvic Acid Breakdown of sixcarbon glucose molecule into 2 threecarbon molecules of pyruvic acid 10 step process occurring in cell cytosol produces 4 molecules of ATP after input of 2 ATP utilizes 2 NAD molecules as hydrogen acceptors lfO2 shortage in a cell pyruvic acid is reduced to lactic acid so that NAD will be still available for further glycolysis rapidly diffuses out of cell to blood liver cells remove it from blood amp convert it back to pyruvic acid Formation ofAcetyl Coenzyme A Pyruvic acid enters the mitochondria with help oftransporter protein Decarboxylation pyruvate dehydrogenase converts 3 carbon pyruvic acid to 2 carbon fragment CO2 produced pyruvic acid was oxidized so that NAD becomes NADH 2 carbon fragment acetyl group is attached to Coenzyme A to form Acetyl coenzyme A which enter Krebs cycle coenzyme A is derived from pantothenic acid B vitamin Krebs Cycle Citric Acid Cycle Series of oxidationreduction amp decarboxylation reactions occurring in matrix of mitochondria lt finishes the same as it starts 4C 7 acetyl CoA 2C enters at top amp combines with a 4C compound 7 2 decarboxylation reactions peel 2 carbons off again when CO2 is formed Krebs Cycle Energy stored in bonds is released step by step to form several reduced coenzymes NADH amp FADH2 that store the energy In summary each Acetyl CoA molecule that enters the Krebs cycle produces 2 molecules of C02 one reason 02 is needed 3 molecules of NADH H one molecule of ATP one molecule of FADH2 39 Remember each glucose produced 2 acetyl CoA molecules The Electron Transport Chain Series ofintegral membrane proteins in the inner mitochondrial membrane capable of oxidationreduction Each electron carrier is reduced as it picks up electrons and is oxidized as it gives up electrons Small amounts ofenergy released in small steps Energy used to form ATP by chemiosmosis Chemiosmosis Small amounts ofenergy released as substances are passed along inner membrane Energy used to pump H ions from matrix into space between inner amp outer membrane High concentration of H is maintained outside of inner membrane ATP synthesis occurs as H diffuses through a special H channel in inner membrane Electron Carriers Flavin mononucleotide FMN is derived from riboflavin vitamin B2 Cytochromes are proteins with heme group iron existing either in reduced form Fe2 or oxidized form Fe3 Ironsulfur centers contain 2 or 4 iron atoms bound to sulfur within a protein Copper Cu atoms bound to protein Coenzyme Q is nonprotein carrier mobile in the lipid bilayer ofthe inner membrane Steps in Electron Transport Carriers ofelectron transport chain are clustered into 3 complexes that each act as proton pump expel H Mobile shuttles pass electrons between complexes Last complex passes its electrons 2H to a half of 02 molecule to form a water molecule H20 Proton Motive Force amp Chemiosmosis Buildup of H outside the inner membrane creates charge 7 electrochemical gradient potential energy is called proton motive force ATP synthase enzyme within H channel uses proton motive force to synthesize ATP from ADP and P Summary of Cellular Respiration Glucose 02 is broken down into C02 H20 energy used to form 36 to 38 ATPs 7 2 ATP are formed during glycolysis 7 2 ATP are formed by phosphorylation during Krebs cycle 7 electron transfers in transport chain generate 32 or 34 ATPs from one glucose molecule Summary in Table 251 Points to remember 7 ATP must be transported out of mitochondria in exchange for ADP uses up some of proton motive force 7 Oxygen is required or many of these steps can not occur Carbohydrate Loading 0 Longterm athletic events marathons can exhaust glycogen stored in liver and skeletal muscles 0 Eating large amounts of complex carbohydrates pasta amp potatoes for 3 days before a marathon maximizes glycogen available for ATP production 0 Useful for athletic events lasting for more than an hour Glycogenesis amp Glycogenolysis Glycogenesis 7 glucose storage as glycogen 7 4 steps to glycogen formation in liver or skeletal muscle 7 stimulated by insulin Glycogenolysis 7 glucose release not a simple reversal of steps 7 enzyme phosphorylase splits offa glucose molecule by phosphorylation to form glucose 1phosphate 7 enzyme only in hepatocytes so muscle can t release glucose 7 enzyme activated by glucagon pancreas amp epinephrine adrenal Gluconeogenesis Liver glycogen runs low if fasting starving or not eating carbohydrates forcing formation from other substances 7 lactic acid glycerol amp certain amino acids 60 of available Stimulated by cortisol adrenal amp glucagon pancreas 7 cortisol stimulates breakdown of proteins freeing amino acids 7 thyroid mobilizes triglycerides from adipose tissue Transport of Lipids by Lipoproteins Most lipids are nonpolar and must be combined with protein to be tranported in blood Lipoproteins are spheres containing hundreds of molecules 7 outer shell polar proteins apoproteins amp phospholipids 7 inner core of triglyceride amp cholesterol esters Lipoprotein categorized by function amp density 4 major classes of lipoproteins 7 chylomicrons very lowdensity lowdensity amp highdensity lipoproteins Classes of Lipoproteins Chylomicrons 2 protein 7 form in intestinal epithelial cells to transport dietary fat apo C2 activates enzyme that releases the fatty acids from the chylomicron for absorption by adipose amp muscle cells liver processes what is left VLDLs 10 protein 7 transport triglycerides formed in liver to fat cells LDLs 25 protein bad cholesterol 7 carry 75 of blood cholesterol to body cells 7 apo B100 is docking protein for receptormediated endocytosis ofthe LDL into a body cell if cells have insuf cient receptors remains in blood and more likely to deposit cholesterol in artery walls plaque HDLs 40 protein good cholesterol 7 carry cholesterol from cells to liver for elimination Blood Cholesterol Sources of cholesterol in the body 7 food eggs dairy organ meats meat 7 synthesized by the liver All fatty foods still raise blood cholesterol 7 liver uses them to create cholesterol 7 stimulate reuptake of cholesterol containing bile normally lost in the feces Desirable readings for adults 7 total cholesterol under 200 mgdL triglycerides 10190 mgdL 7 LDL under 130 mgdL HDL over 40 mgdL 7 cholesterolHDL ratio above 4 is undesirable risk Raising HDL amp lowering cholesterol can be accomplished by exercise diet amp drugs Fate of Lipids Oxidized to produce ATP Excess stored in adipose tissue or liver Synthesize structural or important molecules phospholipids of plasma membranes lipoproteins that transport cholesterol thromboplastin for blood clotting myelin sheaths to speed up nerve conduction cholesterol used to synthesize bile salts and steroid hormones Triglyceride Storage Adipose tissue removes triglycerides from chylomicrons and VLDL and stores it 50 subcutaneous 12 near kidneys 15 in omenta 15 in genital area 8 between muscles Fats in adipose tissue are everchanging released transported amp deposited in other adipose Triglycerides store more easily than glycogen do not exert osmotic pressure on cell membranes are hydrophobic Lipid Catabolism Lipolysis amp Glycerol 39 Triglycerides are split into fatty acids amp glycerol by lipase glycerol if cell ATP levels are high converted into glucose if cell ATP levels are low converted into pyruvic acid which enters aerobic pathway to ATP production Lipolysis amp Fatty acids Beta oxidation in mitochondria removes 2 carbon units from fatty acid amp forms acetyl coenzyme A Liver cells form acetoacetic acid from 2 carbon units amp ketone bodies from acetoacetic acid ketogenesis 7 heart muscle amp kidney cortex prefer to use acetoacetic acid for ATP production Lipid Anabolism Lipogenesis 39 Synthesis of lipids by liver cells lipogenesis from amino acids converted to acetyl CoA amp then to triglycerides from glucose from glyceraldehyde 3phosphate to triglycerides 39 Stimulated by insulin when eat excess calories Ketosis 0 Blood ketone levels are usually very low many tissues use ketone for ATP production 0 Fasting starving or high fat meal with few carbohydrates results in excessive beta oxidation amp ketone production acidosis ketoacidosis is abnormally low blood pH sweet smell of ketone body acetone on breath occurs in diabetic since triglycerides are used for ATP production instead of glucose amp insulin inhibits lipolysis Fate of Proteins 0 Proteins are broken down into amino acids transported to the liver 0 Usage oxidized to produce ATP used to synthesize new proteins enzymes hemoglobin antibodies hormones brinogen actin myosin collagen elastin amp keratin excess converted into glucose or triglycerides no storage is possible 0 Absorption into body cells is stimulated by insulinlike growth factors lGFs amp insulin Protein Catabolism Breakdown of protein into amino acids Liver cells convert amino acids into substances that can enter the Krebs cycle 7 deamination removes the amino group NH2 converts it to ammonia NH3 amp then urea urea excreted in the urine Converted substances enter the Krebs cycle to produce ATP Protein Anabolism Production of new proteins by formation of peptide bonds between amino acids 7 10 essential amino acids are ones we must eat because we can not synthesize them 7 nonessential amino acids can be synthesized by transamination transfer ofan amino group to a substance to create an amino acid Occurs on ribosomes in almost every cell Stimulated by insulinlike growth factor thyroid hormone insulin estrogen amp testosterone Large amounts of protein in the diet do not cause the growth of muscle only weight bearing exercise Phenylketonuria PKU 0 Genetic error of protein metabolism that produces elevated blood levels ofamino acid phenylalanine causes vomiting seizures amp mental retardation normally converted by an enzyme into tyrosine which can enter the krebs cycle 0 Screening of newborns prevents retardation spend their life with a diet restricting phenylalanine restrict Nutrasweet which contains phenylalanine Key Molecules at Metabolic Crossroads Glucose 6 phosphate pyruvic acid and acetyl coenzyme A play pivotal roles in metabolism Different reactions occur because of nutritional status or level of physical activity Role of Glucose 6 Phosphate Glucose is converted to glucose 6 phosphate just after entering the cell Possible fates ofglucose 6 phosphate used to synthesize glycogen when glucose is abundant ifglucose 6 phosphatase is present glucose can be rereleased from the cell precursor ofa vecarbon sugar used to make RNA amp DNA converted to pyruvic acid during glycolysis in most cells of the body Role of Pyruvic Acid 0 3carbon molecule formed when glucose undergoes glycolysis lfoxygen is available cellular respiration proceeds lfoxygen is not available only anaerobic reactions can occur pyruvic acid is changed to lactic acid Conversions amino acid alanine produced from pyruvic acid to oxaloacetic acid of Krebs cycle Role of Acetyl coenzyme A Can be used to synthesize fatty acids ketone bodies or cholesterol Can not be converted to pyruvic acid so can not be used to reform glucose Metabolic Adaptations Absorptive state nutrients entering the bloodstream glucose readily available for ATP production 4 hours for absorption of each meal so absorptive state lasts for 12 hoursday Postabsorptive state absorption of nutrients from GI tract is complete body must meet its needs without outside nutrients late morning late afternoon amp most ofthe evening assuming no snacks lasts about 12 hoursday more cells use ketone bodies for ATP production maintaining a steady blood glucose level is critical Metabolism during Absorptive State Body cells use glucose for ATP production about 50 of absorbed glucose Storage of excess fuels occur in hepatocytes adipocytes amp skeletal muscle most glucose entering liver cells is converted to glycogen 1 0 or triglycerides 40 dietary lipids are stored in adipose tissue amino acids are deaminated to enter Krebs cycle or are converted to glucose or fatty acids amino acids not taken up by hepatocytes used by other cells for synthesis of proteins Regulation of Metabolism during Absorptive State 0 Beta cells of pancreas release insulin 0 lnsulin s functions increases anabolism amp synthesis of storage molecules decreases catabolic or breakdown reactions promotes entry of glucose amp amino acids into cells stimulates phosphorylation ofglucose enhances synthesis oftriglycerides stimulates protein synthesis along with thyroid amp growth hormone Metabolism During Postabsorptive State Maintaining normal blood glucose level 70 to 110 mg100 ml of blood is major challenge glucose enters blood from 3 major sources glycogen breakdown in liver produces glucose glycerol from adipose converted by liver into glucose gluconeogenesis using amino acids produces glucose alternative fuel sources are fatty acids from fat tissue fed into Krebs as acetyl CoA lactic acid produced anaerobically during exercise oxidation of ketone bodies by heart amp kidney Most body tissue switch to utilizing fatty acids except brain still need glucose Regulation of Metabolism During Postabsorptive State As blood glucose level declines pancreatic alpha cells release glucagon glucagon stimulates gluconeogenesis amp glycogenolysis within the liver Hypothalamus detects low blood sugar sympathetic neurons release norepinephrine and adrenal medulla releases norepinephrine amp epinephrine stimulates glycogen breakdown amp lipolysis raises glucose amp free fatty acid blood levels Metabolism During Fasting amp Starvation Fasting means going without food for hoursdays Starvation means weeks or months can survive 2 months or more if drink enough water amount of adipose tissue is determining factor Nutritional needs nervous tissue amp RBC need glucose so amino acids will be broken down for guconeogenesis blood glucose stabilizes at 65 mg1OO mL lipolysis releases glycerol used in guconeogenesis increase in formation of ketone bodies by liver cells due to catabolism of fatty acids by 40 days ketones supply 23 s of brains fuel for ATP Absorption of Alcohol 0 Absorption begins in the stomach but is absorbed more quickly in the small intestine fat rich foods keep the alcohol from leaving the stomach and prevent a rapid rise in blood alcohol a gastric mucosa enzyme breaks down some of the alcohol to acetaldehyde 0 Females develop higher blood alcohols have a smaller blood volume have less gastric alcohol dehydrogenase activity Metabolic Rate 39 Rate at which metabolic reactions use energy energy used to produce heat or ATP 39 Basal Metabolic Rate BMR measurements made under speci c conditions quiet resting and fasting condition 39 Basal Temperature maintained at 986 degrees shell temperature is usually 1 to 6 degrees lower Heat Production 0 Factors that affect metabolic rate and thus the production of body heat exercise increases metabolic rate as much as 15 times hormones regulate basal metabolic rate thyroid insulin growth hormone amp testosterone increase BMR sympathetic nervous system s release of epinephrine amp norepinephrine increases higher body temperature raises BMR ingestion of food raises BMR 1020 children s BMR is double that ofan elderly person Mechanisms of Heat Transfer 0 Temperature homeostasis requires mechanisms oftransferring heat from the body to the environment conduction is heat exchange requiring direct contact with an object convection is heat transfer by movement of gas or liquid over body radiation is transfer of heat in form of infrared rays from body evaporation is heat loss due to conversion of liquid to a vapor insensible water loss Hypothalamic Thermostat Preoptic area in anterior hypothalamus receives impulses from thermoreceptors generates impulses at a higher frequency when blood temperature increases impulses propagate to other parts of hypothalamus heatlosing center heatpromoting center 0 Set in motion responses that either lower or raise body temperature Thermoregulation Declining body temperature 7 thermoreceptors signal hypothalamus to produce TRH 7 TRH causes anterior pituitary to produce TSH resulting in vasoconstriction in skin adrenal medulla stimulates cell metabolic rate shivering release of more thyroid hormone raises BMR Increases in body temperature 7 sweating amp vasodilation Hypothermia Lowering of core body temperature to 35 C 95 F Causes immersion in icy water cold stress metabolic diseases hypoglycemia adrenal insuf ciency or hypothyroidism drugs alcohol antidepressants or sedatives burns and malnutrition Symptoms that occur as body temperature drops shivering confusion vasoconstriction muscle rigidity bradycardia acidosis hypoventilation coma amp death Regulation of Food Intake Hypothalamus regulates food intake feeding hunger center satiety center Stimuli that decrease appetite glucagon cholecystokinin epinephrine glucose amp leptin stretching ofthe stomach and duodenum Signals that increase appetite growth releasing hormone opioids glucocorticoids insulin progesterone amp somatostatin Guidelines for Healthy Eating Nutrients include water carbohydrates lipids proteins vitamins and minerals Caloric intake women 1600 Caloriesday is needed active women and most men 2200 Calories teenage boys and active men 2800 calories Food guide pyramid developed by US Department of Agriculture indicates number of servings of each food group to eat each day Minerals Inorganic substances 4 body weight Functions calcium amp phosphorus form part of the matrix of bone help regulate enzymatic reactions calcium iron magnesium amp manganese magnesium is catalyst for conversion ofADP to ATP form buffer systems regulate osmosis of water generation of nerve impulses Vitamins Organic nutrients needed in very small amounts serve as coenzymes Most cannot be synthesized by the body Fatsoluble vitamins absorbed with dietary fats by the small intestine stored in liver and include vitamins A D E and K Watersoluble vitamins are absorbed along with water in the GI tract body does not storeexcess excreted in urine includes the B vitamins and vitamin C An Vit tioxidant Vitamins C E and betacarotene a provitamin Inactivate oxygen free radicals highly reactive particles that carry an unpaired electron damage cell membranes DNA and contribute to atherosclerotic plaques arise naturally or from environmental hazards such as tobacco or radiation Protect against cancer aging cataract formation and atherosclerotic plaque amin and Mineral Supplements Eat a balanced diet rather than taking supplements Exceptions iron for women with heavy menstrual bleeding iron amp calcium for pregnant or nursing women folic acid if trying to become pregnant reduce risk of fetal neural tube defects calcium for all adults B12 for strict vegetarians antioxidants C and E recommended by some ver Abnormally high body temperature toxins from bacterial or viral infection pyrogens heart attacks or tumors tissue destruction by xrays surgery or trauma reactions to vaccines Bene cial in fighting infection amp increasing rate of tissue repair during the course ofa disease Complicationsdehydration acidosis amp brain damage Obesity Body weight more than 20 above desirable standard Risk factor in many diseases cardiovascular disease hypertension pulmonary disease noninsulin dependent diabetes mellitus arthritis certain cancers breast uterus and colon varicose veins and gallbladder disease
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