Carbohydrate Metabolism

CARBOHYDRATE METABOLISM

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I. Polysaccharide to Monosaccharide • Digestion II. Monosaccharide to Acetyl CoA • Glucose -> Acetyl CoA -> Citric Acid Cycle III. Oxidative Phosphorylation

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STEP 1: DIGESTION • MOUTH – doughnut (cellulose, amylase, amylopectin, lactose) o α amylase (ptyalin) – capable of breaking α 1,4 bonds o basic – optimal pH of AMYLASE • STOMACH o pH is ACIDIC o stops the digestion of carbohydrate because of acidic nature • INTESTINE o α AMYLASE from pancreas breaks the remaining α 1,4 bonds o α dextrinase – breaks α 1,6 o α glucosidase – breaks α 1,4 o disaccharidases (maltase, lactase) – breaks disaccharides into monosaccharide o cellulose and monosaccharides remain o monosaccharides – will be absorbed in the small intestine by entering the lumen to enter the blood circulation ACTIVE TRANSPORT – Co-transport PASSIVE TRANSPORT – facilitated diffusion CARRIERS: GLUT1 – GLUT5 (GLUCOSE TRANSPORTERS • GLUT4 o transports glucose under the influence of the hormone INSULIN o can be found in adipose tissues and skeletal muscles • brain, liver, RBC and intestines doesn’t need INSULIN STEP 2: GLYCOLYSIS – process of breaking down glucose to provide energy in the form of ATP and to provide intermediates • TYPES: o AEROBIC – mitochondria in the presence of O2 o ANAEROBIC – cells without mitochondria • PHASES: o ENERGY INVESMENT PHASE o ENERGY GENERATION PHASE

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Consists of 10 reactions with 3 regulated steps Each molecule of glucose produces 4 molecules of ATP STEPS: o 1: PHOSPHORYLATION OF GLUCOSE  Irreversible  Requires ATP  Glycolysis – occurs in CYTOSOL  Glucose should be trapped inside the cell by adding phosphate  HEXOKINASE • Very high affinity for glucose • Found in most tissues • Broad specificity: can be used in hexoses not only for glucose • Low Km and Vmax for glucose • Can be inhibited by G6P (glucose-6phosphate) – negative feedback of glycolysis • Not influenced by insulin • Can easily be saturated  GLUCOKINASE • Low affinity for glucose • High Km for glucose found in the liver & B cells of the pancreas • High Vmax for glucose suitable for the liver (receives high amounts of glucose) • can phosphorylate high amounts of glucose • Not inhibited by G6P unlike hexokinase • Not influenced by insulin because it is in the liver o 2: ISOMERIZATION OF G6P – change aldose to ketose  Catalyzed by PHOSPHOGLUCOSE ISOMERASE

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G6P -> F6P (fructose-6phosphate)  Reversible step 3: PHOSPHORYLATION OF F6P  Irreversible  Rate-limiting – primary control of how much glycolysis will occur  Mediated by enzyme PHOSPHOFRUCTOKINASE 1 (PFK1)  Most important control step in glycolysis  ENZYMATIC ACTIVITY OF PFK1:

INCREASED AMP (energy starved Insulin Well fed state Fructose-2,6Biphosphate

High amounts of ATP will inhibit the activity of PFK1  Decreased glucagon will result into starvation  Insulin is pro-storage while glucagon is antistorage/pro-degradation 4-5: CLEAVAGE OF F1,6BP  ALDOLASE A – cleaves F1,6BP into DIHYDROXYACETONE PHOSPHATE & GLYCERALDEHYDE-3PHOSPHATE (TRIOSE)  DHAP & G3P – only involved in glycolysis; interchangeable  TRIOSE PHOSPHATE ISOMERASE – enzymes 6: OXIDATION OF G3P  Catalyzed by G3P dehydrogenase  First oxidation-reduction reaction of glycolysis  Elemental phosphate is added to G3P to form 1,3BPG  BIPHOSPHOGLYCERATE MUTASE  Oxidation reaction will remove the H+  Reduction reaction will gain the H+ 7: 1,3BPG to 3PG  1,3BPG is converted to 3PG 

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DECREASED ATP (energy rich) Glucagon Fasting State

Produces ATP in the process Catalyzed by PHOSPHOGLYCERATE KINASE  Reversible  SUBSTRATE LEVEL PHOSPHORYLATION (SLP) 8: 3PG to 2PG  Catalyzed by PHOSPHOGLYCERATE MUTASE  Mutate from 3 to 2 phosphate group 9: DEHYDRATION OF 2PHOSPHOGLYCERATE  2-PHOSPHOGLYCERATE is dehydrated by ENOLASE to from PHOSPHOEOLPYRUVATE (PEP)  Reversible 10: FORMATION OF PYRUVATE  Final step in glycolysis  PYRUVATE KINASE  Irreversible reaction  Forms ATP (SLP)  Pyruvate kinase is activated by F1,6BP (feed forward reaction)  Ensures that the reaction goes forward once PFK converts F6P into F1,6BP  Increased glucagon -> decreased pyruvate kinase activity  

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3 IMPORTANT STEPS (IRREVERSIBLE): 1. (1) PHOSPHORYLATION OF GLUCOSE 2. (3) PHOSPHORYLATION OF F6P 3. (10) FORMATION OF PYRUVATE WHAT HAPPENS TO PYRUVATE? 1. OXIDATIVE CARBOXYLATION  Enters the trycarboxylic acid cycle  Gets converted to Acetyl CoA by PYRUVATE DEHYDROGENASE 2. CAN BE CARBOXYLATED INTO OXALOACETATE  The first step in GLUCOGENESIS 3. PYRUVATE CONVERTED TO ETHANOL 4. PYRUVATE TO LACTATE Pyruvate + NADH + H -> lactate + NAD + 2H ENERGY YIELD OF GLYCOLYSIS  2 invested ATP  4 gained ATP  ETC = total of 8: (10 – 2) o NADH: 3 ATP x 2 = 6

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o FADH: 2 ATP x 2 = 4 Overall reaction: o ANAEROBIC – glucose to pyruvate o AEROBIC – glucose to lactate

IN SUMMARY, GLYCOLYSIS:  Uses 2 molecules of ATP per glucose molecule to convert it to pyruvate  Produces 4 molecules of ATP  2 net ATP  2 molecules f NADH are produced  3 ATP produced per molecule of NADH if the reaction proceeds to oxidative phosphorylation  2 ATP/glucose  3 regulated steps: 1,3,10  Glucose -> Pyruvate

-Rosette Go 091808 