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METABOLISM Metabolism 1. Metabolism – all chemical reactions necessary to maintain life 2. Catabolism – breakdown from complex to simple *Chemical reactions in which complex molecules are broken down to simple ones: a. anabolism b. catabolism c. reduction d. oxidation 3. Anabolism – synthetic reaction; from simple to complex 4. Oxidation – the gain of oxygen or loss of hydrogen; loss of energy (electron) 5. Reduction – the gain of hydrogen or loss of oxygen; gain of energy (electron) *This results from the gain of hydrogen or loss of oxygen: a. anabolism b. catabolism c. reduction d. oxidation 6. Redox – whenever one compound is reduced, another is oxidized 7. Coenzymes – temporary hydrogen (or electron) acceptor -a. NAD+ (nicotinamide adenine dinucleotide) – from niacin -b. FAD (flavin adenine dinucleotide) – from riboflavin, B2 8. ATP synthesis – captured energy *This coenzyme is derived from riboflavin: a. ATP b. cyclic AMP c. FAD d. NAD+ -a. Substrate level phosphorylation –phosphate from phosphorylated substrate -b. Oxidative phosphorylation – H+ pass through ATPase channels; gradient energy -c. Chemiosmotic process – food energy (chem) push H+ across membrane (osmotic) Carbohydrate Metabolism 1. Glucose – all carbohydrates are broken down to; taken up by body cells *All carbohydrates are broken down to this: a. glucagon b. glucose c. glycine d. glycogen 2. Glucose-6-phosphate – 1 ATP -ADP; trapped in all but liver, kidney, intestine cell 3. Glucose oxidation – cellular respiration; ATP production -a. C6H1206 + 6O2→6H2O + 6CO2 + 36 ATP + heat 4. Glycogen metabolism – glycogenesis and glycogenolysis 5. Gluconeogenesis – convert glycerol and amino acids to glycogen Glucose oxidation: glycolysis 1. Sugar activation – energy investment phase -a. Glucose – 2 ATP to 2 ADP: add phosphate on -b. Fructose-1,6-diphosphate – the end product of sugar activation 2. Sugar cleavage – fructose-1,6-diphosphate cleaved; 2 3 carbon isomers -a. Dihydroxyacetone phosphate – one isomer; converts to other isomer -b. Glyceraldehyde phosphate – other isomer; convert to other isomer 3. Oxidation: ATP formation -a. Phosphorylation – another phosphate group added to each substrate -b. ATP production – substrate level phosphorylation; 2 per molecule; 4 (-2) -c. NADH+H+ - reduced coenzyme NAD+; 1 per molecule; 2 total -d. Pyruvic acid – 2 molecules; end product of glycolysis *The end product of glycolysis is: a. b. c. d. glycerol glycogen acetyl coenzyme A pyruvic acid *Glycolysis results in the net formation of _____ molecules of ATP per glucose: a. b. c. d. 1 2 8 16 Glucose oxidation: anaerobic versus aerobic 1. Anaerobic – NADH+H+ returns hydrogens to pyruvic acid; lactic acid -a. Lactic acid – diffuse out of cell; back to liver -b. Acid-base problems – some tissue tolerate (muscle); cardiac less; brain not at all 2. Aerobic – pyruvic acid to mitochondria fluid matrix Glucose oxidation: Acetyl Coenzyme formation 1. Decarboxylation – one of pyruvic acids carbon removed; CO2; total 2 2. Oxidation – Hydrogen ions are removed 3. NADH+H+- coupled reduction of NAD+; total 2 4. Acetic acid – by product 5. Coenzyme A – from pantothenic acid (B5); combines with acetic acid; acetyl CoA 6. Acetyl CoA – on to Kreb’s cycle *This molecule enters the Kreb’s cycle: a. acetone b. acetyl CoA c. lactic acid d. pyruvic acid Glucose oxidation: Kreb’s (citric acid) cycle 1. Acetyl CoA – enters the Kreb’s cycle 2. Oxaloacetic acid – combines with acetic acid, which disassociated from CoA 3. Citric acid – where cycle gets its name 4. Decarboxylation – for each acetyl CoA, 2 C removed as 2CO2; total 4 5. NADH+H+ - reduction of NAD+; 3 per acetyl CoA; total 6 6. FADH2 – reduction of FAD; 1 per acetyl CoA: total 2 7. Oxidation – hydrogen removal from intermediates coupled to coenzyme reduction 8. ATP production – GTP; substrate level phosphorylation; 1 per acetyl CoA; total 2 Glucose oxidation: Electron transport chain 1. Cristae – inner mitochondrial membrane; where it takes place *The electron transport chain is located here: a. cytosol b. inner mitochondrial membrane c. outer mitochondrial membrane d. plasma membrane 2. Components – of the electron transfer chain; proteins bound to metal ions -a. Flavins – flavin mononucleotide (FMN); from riboflavin (B2); to protein -b. Cytochoromes – iron containing pigments; mostly 3. Respiratory enzyme complex – three of them; grouped together -a. Coenzyme oxidation – hydrogen is split into H+ and e-; e- moved along -b. H+ pump – at each complex; use energy from the movement of e-c. Matrix – watery; Hydrogen is pumped out of -d. Intermembrane space – hydrogen is pumped into 4. ATP synthase – uses electrical energy of H+ returning to matrix; makes ATP *ATP synthase uses the movement of this ion to make ATP: a. calcium b. hydrogen c. potassium d. sodium 5. Reduced cofactors – carry the electron and hydrogen -a. NADH+H+ - each results in movement of 3 H+; the production of 3 ATP -b. FADH2 – each results in movement of 2 H+; production of 2 ATP 6. Oxygen – has the highest affinity for e-; binds to hydrogen -a. 2H (2H++2e-) + ½O2 → H2O -b. Physiological water – the water resulting from cellular respiration 7. ATP – 2, glycolysis; 2, Krebs cycle; 34, transport chain; minus 2; 36 ATP Glycogen metabolism 1. Glycogenesis – high ATP levels, glycolysis stops; glucose stored as glycogen -a. Hexokinase – in all body cells; uses ATP to ADP to phosphorylate glucose -b. Glucose-6-phosphate – trapped in most body cells *Glucose-6-phosphate can be converted back to glucose here: a. adipose tissue b. adrenal gland c. cardiac muscle d. liver -c. Glucose-1-phosphate – isomer of G6P -d. Glycogen synthase – phase in between; glucose added to glycogen chain -e. Skeletal muscle – does this a lot -f. Liver – also does this; stores glucose for rest of body 2. Glycogenolysis – from low blood glucose level; glucagon -a. Glycogen phosphorylase – cleaves off glucose monomers -b. Glucose-1-phosphate – isomer -c. Glucose-6-phosphate – can be used in glycolysis - d. Glucose-6-phosphatease – G6P back to glucose; liver (kidney and intestinal) Gluconeogenesis 1. Gluconeogenesis – glucose from noncarbohydrate sources; proteins and glycerol 2. Liver – where this takes place 3. Hypoglycemia – the trigger for this to take place 4. Protection – protects nervous system Lipid metabolism: catabolism 1. Lipolysis – stored fats are broken down to glycerol and fatty acids 2. Glycerol oxidation– to glyceraldehyde phosphate; a glycolysis intermediate -a. Glyceraldehyde phosphate – plugged into glycolysis; 18 ATP -b. Gluconeogenesis – all phases of glycolysis are reversible; to glucose-6-phosphate 3. Fatty acids oxidation– are broken down by beta oxidation; in mitochondria -a. Beta oxidation – fatty acid chains are broken down; from carboxyl side; 2 carbon *Fatty acids are broken down by: a. alpha oxidation b. beta oxidation c. alpha reduction d. glycolysis -b. Reduced coenzymes – NADH+H+ and FADH2 are formed -c. Acetic acid – by product of beta oxidation -d. Acetyl Coenzyme A – formed when acetic acid combines with coenzyme A -e. Krebs cycle – acetyl Co A enters 4. Ketone bodies – include acetone; from acetyl co A; can’t be fed into Krebs cycle -a. Ketosis – ketone bodies; diabetes, low carbohydrate diet; metabolic acidosis *Too many of these by products lipolysis can lead to acidosis: a. glycerol b. glycine c. ketone bodies d. cholesterol Lipid metabolism: anabolic 1. Lipogenesis – reverse of lipolysis; glycerol and fatty acids; dehydration synthesis -a. Glycerol – from glyceraldehyde phosphate; glycolysis intermediate -b. Fatty acids – from acetyl coenzyme A 2. Structural materials – many are synthesized from -a. Cell membrane – phospholipids and cholesterol needed; myelin sheath -b. Liver – lipoprotein (transport); tissue factor; cholesterol -c. Cholesterol – from acetyl coenzyme A; steroidal hormones; vitamin D Amino acid oxidation: catabolic 1. Transamination – in liver, amino and oxygen between amino and keto acids -a. α-Ketoglutaric acid – keto acid of Krebs cycle, receives amino group -b. Glutamic acid – amino acid, what the α-ketoglutaric acid -c. Keto acid – the original amino acid; amino group now an oxygen 2. Oxidative deamination – removal of amino group from glutamic acid -a. α-Ketoglutaric acid – is reconstituted, back to Krebs cycle *Oxidative deamination of glutamic acid results in the release of this toxic substance: a. ammonia b. carbon monoxide c. lactic acid d. pyruvate -b. Ammonia – what the amino group becomes; toxic -c. Urea – ammonia combines with carbon dioxide; removed in urine 3. Keto acid modification – into some intermediate in cellular respiration -a. Krebs cycle intermediate – acetyl CoA, α-ketoglutaric acid, or oxaloacetic acid -b. Pyruvic acid – from keto acid modification; used for energy or -d. Gluconeogenesis – glycolysis is reversible; glucose from pyruvic acid Proteins / amino acids: anabolic 1. Protein synthesis – mRNA, tRNA; transcription, translation; ribosomes 2. Nonessential amino acids – transamination of keto acids in the liver, mostly *The formation of most nonessential amino acid occurs here: a. intestine b. liver c. kidney d. skin Absorptive state 1. Absorptive state – fed state; nutrients flushing into blood from intestine 2. Anabolism – outweighs catabolic ones 3. Glucose – major fuel; excess stored as glycogen or fat *During the absorptive state this is the major fuel used by the body: a. amino acids b. lipids c. glycogen d. glucose 4. Amino acids – most used to replenish body proteins 5. Triglycerides – broken down, used as fuel; taken up resynthesized by adipose 6. Insulin – released due to high blood glucose; cause body cells to take up glucose Postabsorptive state 1. Postabsorptive state – empty small intestine; energy from breakdown of reserves 2. Catabolism – breakdown of reserves *Of the following which is less likely to occur during the postabsorptive state? a. lipid synthesis b. glycogenolysis c. gluconeogenesis d. glucose sparing 3. Glucose – homeostatic mechanism; maintain about 100 mg/ 100 ml blood -a. Glycogenolysis – liver; skeletal muscle to pyruvic acid, back to liver -b. Gluconeogenesis – several sources; pyruvic acid from muscle -c. Glucose sparing – organs which can use other fuels 4. Lipolysis – in liver and adipose tissue -a. Glycerol – converted to glucose; gluconeogenesis in liver -b. Fatty acids – directly or used by cells after liver converts to ketone bodies 5. Proteins – after carbohydrate and fats; skeletal muscle first to go 6. Glucagon – causes glycogenolysis and gluconeogenesis; lipolysis of adipocytes 7. Sympathetic nervous system – causes epinephrine release by adrenal medulla -a. Lipolysis – in adipose tissue increased -b. Glycogenolysis – stimulated in muscle and liver -c. Gluconeogenesis – stimulated in liver Metabolic role of liver: general 1. Carbohydrates – glycogenolysis; glycogenogensis; glucose to lipids 2. Protein metabolism – most plasma proteins; deamination; nonessential AAs 3. Urea – formed to get rid of toxic ammonia from deamination & intestinal bacteria 4. Fats – beta oxidation; acetyl CoA; ketone bodies; cholesterol synthesis 5. Vitamin storage – vitamins A, D, and B12 6. Iron storage – most not in RBCs in liver as ferritin 7. Detoxification – of drugs and alcohol Metabolic role of liver: cholesterol regulation 1. Chylomicrons – intestine; lymph to blood; lose some triglycerides; back to liver 2. VLDL – from liver; deliver triglycerides to adipose (mostly) and other tissue 3. LDL – from VLDL; cholesterol to body cells; endocytosis 4. HDL – protein shell made in liver; excess cholesterol back to liver; bile salts *These lipoproteins transport excess cholesterol back to the liver: a. chylomicrons b. VLDL c. LDL d. HDL BODY ENERGY BALANCE Regulation of food intake 1. Hypothalamus – control hunger and satiety 2. Nutrient levels – glucose receptors in brain; high glucose levels inhibit hunger 3. Leptin – protein from adipose tissue; high reserve, high leptin, inhibits hunger 4. Insulin – an important satiety signal 5. Other hormones – epinephrine, hunger; cholecystokinin, satiety *This part of the brain controls hunger: a. basal nuclei b. thalamus c. hypothalamus d. pineal 6. Body temperature – high temperatures depress hunger 7. Psychological factors – can override automatic factors 8. Hypothetical model – interrelationship of factors that control food intake -a. Leptin – a satiety signal produced by adipose tissue -b. Hypothalamus – leptin acts on -c. Neuropeptide Y – an appetite stimulant produced by hypothalamus, is inhibited Metabolic rate 1. Metabolic rate – body’s rate of energy output; kcal/hour 2. Calorimeter – direct measure; heat produced by energy raises water temperature 3. Respirometer – indirect measure; oxygen consumption related to energy output 4. Basal metabolic rate – at rest; postabsorptive state; energy for basal functions -a. 70 kcal/hour – for a normal 70 kg (154 lb) -b. Influences – age, sex, stress, thyroxine 5. Total metabolic rate – to fuel all organic activities -a. Skeletal muscle – activity causes greatest increase -b. Dietary thermogenesis – food intake increases TMR; especially proteins Regulation of body temperature 1. Body temperature – balance between heat production and heat loss 2. Skeletal muscle – produce much of the heat 3. Average body temperature – 36.2 C (98.2 F); homeostatic range 4. Over homeostatic range – depressed neurons; proteins denature; 106 convulsions 5. Under homeostatic range – more tolerated; used in heart surgery 6. Core body temperature – brain, thoracic and abdominal cavity; constant 7. Shell body temperature – fluctuates 20 to 40 degrees C 8. Heat exchange – always from hotter to colder -a. Radiation – loss of heat in form of infrared waves -b. Conduction – direct contact; heat transferred -c. Convection – air warmed by conduction moved away; replaced by cooler -d. Evaporation – of sweat; mucosa; water molecules absorb energy; evaporate 9. Hypothalamus – among others; chief controller of body temperature regulation 10. Heat promoting mechanisms – initiated by the hypothalamus -a. Cutaneous vasoconstriction – slows down heat loss; frostbite -b. Chemical thermogenesis – norepinephrine; increased metabolic rate -c. Shivering – involuntary contraction of skeletal muscle -d. Thyroxine – enhanced release; seasonal changes; gradual; more released, winter -e. Behavior – more clothes; hot drinks 11. Heat loss mechanisms – again, initiated by the hypothalamus -a. Cutaneous vasodialtion – increase heat loss to the skin -b. Sweating – heat loss by evaporation -c. Behavior – take off clothes; slow down; get out of sun -d. Heat exhaustion – dehydration; low BP; confusion; cooling mechanism working -e. Heat stroke – hypothalamus depressed; heat incresses metabolism; brain damage NUTRITION General 1. Kilocalorie – energy to raise 1 kilogram water 1 degree Celsius 2. Nutrient – needed for growth, maintenance, and repair 3. Categories – carbohydrates, proteins, lipids, vitamins, minerals, and water 4. Food groups – grains; fruits; vegetable; meat; and dairy 5. Essential nutrients – not synthesized by body; must be obtained in diet Carbohydrates 1. Sources – complex from starch food; simple from sweet foods 2. Use in body – mostly glucose as fuel; nucleic acids and cell membrane 3. Deficits – proteins and fats broken down; wasting and metabolic acidosis 4. Excesses – obesity; especially simple carbohydrates Lipids 1. Sources – animal (saturated); plants (unsaturated) 2. Use in body – energy; cell membrane; insulation; padding; hormones 3. Deficits – weight loss; loss of adipose tissue; staying warm 4. Excesses – obesity; atherosclerosis Proteins 1. Sources – both plant and animal sources -a. Complete proteins – animal sources; meat; eggs; dairy -b. Incomplete proteins - plant sources -c. Essential amino acids – must be obtained from diet 2. Use in body – structure; function (enzymes, hemoglobin); fuel if needed 3. Deficits – tissue wasting; growth retardation; anemia 4. Excesses – obesity Vitamins 1. Vitamins – organic molecules; coenzyme or part; helps enzyme catalyze 2. Source – most we can’t make; bacteria K and pantothenic acid (B); vitamin D -a. Provitamin – like β carotene; used to make vitamin A (retinol) 3. Water soluble – C and B complex -a. Absorption – most with water in GI tract; B12 needs intrinsic factor -b. Hypervitaminosis – rare with water soluble; not stored in body 4. Fat soluble – A, D, E, and K *Of the following which is not a fat soluble vitamin? a. A b. B c. D d. E -a. Absorption – with fats in GI tract -b. Hypervitaminosis – all except K can accumulate in body 5. Antioxidants – A, C, and K disarm free radicals; superoxide ion; anticancer Fat soluble vitamins 1. Vitamin A – retinal; photopigment synthesis; skin, mucosa, skin, bone, repro -a. Source - β carotene; yellow, green vegetables; liver; egg yolk 2. Vitamin D – antirachitic factor; calcium absorption in intestine -a. Source – UV light; made in skin; fish liver oil; egg yolk 3. Vitamin E – antisterility factor; antioxidant; protects cell membrane -a. Source – wheat germ; vegetable oil; nuts 4. Vitamin K – coagulation vitamin; liver synthesis; coagulation and other proteins -a. Source – mostly enteric bacteria Water soluble vitamins 1. Vitamin C – ascorbic acid; connective tissue formation; serotonin; bile salts -a. Source – fruits and vegetable; citrus fruits 2. Vitamin B1 – thiamine; carbohydrate metabolism 3. Vitamin B2 – riboflavin; cellular respiration 4. Niacin – nicotinamide; also cellular respiration 5. Vitamin B6 – pyridoxine; amino acid metabolism 6. Vitamin B5- pantothenic acid; cellular respiration; fat oxidation and synthesis 7. Biotin – Krebs cycle; nonessential amino acid synthesis 8. B12 – cyanocobalamin; in GI tract; nervous system; red marrow DNA synthesis 9. Folic acid – folacin; amino acid; DNA synthesis; red blood cell formation Minerals 1. Calcium (Ca) – bones; blood clotting; normal muscle and nervous functioning -a. Source – dairy; leafy green vegetables 2. Chlorine (Cl) – Cl- chief anion in extracellular fluid; Cl shift; HCl in stomach 3. Sulfur – proteins (disulfide bonds); vitamins (biotin, thiamine); connective tissue 4. Potassium (K) – intracellular cation; osmotic pressure; nerve, muscle function 5. Sodium (Na) – cation in extracellular fluid; osmotic pressure; neuromuscular 6. Magnesium (Mg) – ATP to ADP; muscle and nerve irritability -a. Source – dairy; nuts; green vegetables 7. Phosphorus (P) – bone, teeth, nucleic acids, ATP, phospholipids Trace minerals 1. Fluorine (F) – tooth structure; prevent dental caries; osteoporosis -a. Source – fluoridated water 2 Cobalt (Co) – part of vitamin B12; red blood cell maturation 3. Chromium (Cr) – glucose metabolism; enhanced effectiveness of insulin 4. Copper (Cu) – hemoglobin synthesis; electron transport chain 5. Iodine (I) – thyroid metabolism -a. Source – iodized salt; shellfish; cod liver oil 6. Iron (Fe) – hemoglobin; cytochromes in oxidative phosphorylation 7. Manganese (Mn) – synthesis of lipids; hemoglobin; neural function -a. Source – nuts; legumes; leafy green vegetables 8. Selenium (Se) – antioxidant; spares vitamin E 9. Zinc (Zn) – in several enzymes; carbonic anhydrase