Carbohydrate MetabolismAn OverviewGeneral Biochemistry-II (BCH 302) Dr . Saba AbdiAsst . Prof. Dept. Of BiochemistryCollege Of ScienceKing Saud University. Riyadh.KSA

Major Pathways1. Glycolysis2. Citric acid cycle3. Gluconeogenesis4. Glycogen metabolism (a) Glycogenesis (b) Glycogenolysis*Saba Abdi

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I. Glycolysis (Embden Meyerhof Pathway): A. Definition: 1. Glycolysis means oxidation of glucose to give pyruvate (in the presence of oxygen) or lactate (in the absence of oxygen). B. Site: cytoplasm of all tissue cells, but it is of physiological importance in: 1. Tissues with no mitochondria: mature RBCs, cornea and lens. 2. Tissues with few mitochondria: Testis, leucocytes, medulla of the kidney, retina, skin and gastrointestinal tract. 3. Tissues undergo frequent oxygen lack: skeletal muscles especially during exercise.*Saba Abdi

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C. Steps: Stages of glycolysis 1. Stage one (the energy requiring stage): a) One molecule of glucose is converted into two molecules of glycerosldhyde-3-phosphate. b) These steps requires 2 molecules of ATP (energy loss) 2. Stage two (the energy producing stage(: a) The 2 molecules of glyceroaldehyde-3-phosphate are converted into pyruvate (aerobic glycolysis) or lactate (anaerobic glycolysis(. b) These steps produce ATP molecules (energy production). *Saba Abdi

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Fig. 9.9aEnergy Investment Phase (steps 1-5)*Saba Abdi

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Fig. 9.9bEnergy-Payoff Phase (Steps 6-10)*Saba Abdi

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Energy production of glycolysis: *Saba Abdi

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E. oxidation of extramitochondrial NADH+H+: 1. cytoplasmic NADH+H+ cannot penetrate mitochondrial membrane, however, it can be used to produce energy (4 or 6 ATP) by respiratory chain phosphorylation in the mitochondria. 2. This can be done by using special carriers for hydrogen of NADH+H+ These carriers are either dihydroxyacetone phosphate (Glycerophosphate shuttle) or oxaloacetate (aspartate malate shuttle). a) Glycerophosphate shuttle: 1) It is important in certain muscle and nerve cells. 2) The final energy produced is 4 ATP. 3) Mechanism:- The coenzyme of cytoplasmic glycerol-3- phosphate dehydrogenase is NAD+.- The coenzyme of mitochodrial glycerol-3-phosphate dehydogenase is FAD.- Oxidation of FADH, in respiratory chain gives 2 ATP. As glycolysis gives 2 cytoplasmic NADH + H+ 2 mitochondrial FADH, 2 x 2 ATP = 4 ATP. b) Malate aspartate shuttle: 1) It is important in other tissues patriculary liver and heart. 2) The final energy produced is 6 ATP.*Saba Abdi

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Differences between aerobic and anaerobic glycolysis:*Saba Abdi

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Importance of lactate production in anerobic glycolysis: 1. In absence of oxygen, lactate is the end product of glycolysis:

2. In absence of oxygen, NADH + H+ is not oxidized by the respiratory chain. 3. The conversion of pyruvate to lactate is the mechanism for regeneration of NAD+. 4. This helps continuity of glycolysis, as the generated NAD+ will be used once more for oxidation of another glucose molecule. Glucose Pyruvate Lactate

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Substrate level phosphorylation: This means phosphorylation of ADP to ATP at the reaction itself .in glycolysis there are 2 examples: - 1.3 Bisphosphoglycerate + ADP 3 Phosphoglycerate + ATP - Phospho-enol pyruvate + ADP Enolpyruvate + ATPI. Special features of glycolysis in RBCs: 1. Mature RBCs contain no mitochondria, thus: a) They depend only upon glycolysis for energy production (=2 ATP). b) Lactate is always the end product. 2. Glucose uptake by RBCs is independent on insulin hormone. 3. Reduction of met-hemoglobin: Glycolysis produces NADH+H+, which used for reduction of met-hemoglobin in red cells. *Saba Abdi

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Biological importance (functions) of glycolysis: 1. Energy production: a) anaerobic glycolysis gives 2 ATP. b) aerobic glycolysis gives 8 ATP. 2. Oxygenation of tissues: Through formation of 2,3 bisphosphoglycerate, which decreases the affinity of Hemoglobin to O2. 3. Provides important intermediates: a) Dihydroxyacetone phosphate: can give glycerol-3phosphate, which is used for synthesis of triacylglycerols and phospholipids (lipogenesis). b) 3 Phosphoglycerate: which can be used for synthesis of amino acid serine. c) Pyruvate: which can be used in synthesis of amino acid alanine. 4. Aerobic glycolysis provides the mitochondria with pyruvate, which gives acetyl CoA Krebs' cycle.

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Reversibility of glycolysis (Gluconeoqenesis): 1. Reversible reaction means that the same enzyme can catalyzes the reaction in both directions. 2. all reactions of glycolysis -except 3- are reversible. 3. The 3 irreversible reactions (those catalyzed by kinase enzymes) can be reversed by using other enzymes.Glucose-6-p Glucose F1, 6 Bisphosphate Fructose-6-pPyruvate Phosphoenol pyruvate 4. During fasting, glycolysis is reversed for synthesis of glucose from non- carbohydrate sources e.g. lactate. This mechanism is called: gluconeogenesis.*Saba Abdi

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As pyruvate enters the mitochondrion, a multienzyme complex modifies pyruvate to acetyl CoA which enters the Krebs cycle in the matrix.A carboxyl group is removed as CO2.A pair of electrons is transferred from the remaining two-carbon fragment to NAD+ to form NADH.The oxidized fragment, acetate, combines with coenzyme A to form acetyl CoA.Fig. 9.10*Saba Abdi

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Kreb Cycle*Saba Abdi

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Electron Transport Chain*Saba Abdi

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Summary*Saba Abdi

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Total energy yieldGlycolysis 2 ATPKrebs Cycle 2 ATPETC 32 ATP

Total 36 ATP

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Glycogen Metabolism*Saba Abdi

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Glycogenesis:

Glycogenesis is the formation of glycogen from glucose. Glycogen is synthesized depending on the demand for glucose and ATP (energy). If both are present in relatively high amounts, then the excess of insulin promotes the glucose conversion into glycogen for storage in liver and muscle cells.In the synthesis of glycogen, one ATP is required per glucose incorporated into the polymeric branched structure of glycogen. actually, glucose-6-phosphate is the cross-roads compound. Glucose-6-phosphate is synthesized directly from glucose or as the end product of gluconeogenesis.

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Glycogenolysis

In glycogenolysis, glycogen stored in the liver and muscles, is converted first to glucose-1- phosphate and then into glucose-6-phosphate. Two hormones which control glycogenolysis are a peptide, glucagon from the pancreas and epinephrine from the adrenal glands.Glucagon is released from the pancreas in response to low blood glucose and epinephrine is released in response to a threat or stress. Both hormones act upon enzymes to stimulate glycogen phosphorylase to begin glycogenolysis and inhibit glycogen synthetase (to stop glycogenesis).

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.Glycogen is a highly branched polymeric structure containing glucose as the basic monomer. First individual glucose molecules are hydrolyzed from the chain, followed by the addition of a phosphate group at C-1. In the next step the phosphate is moved to the C-6 position to give glucose 6-phosphate, a cross road compound.Glucose-6-phosphate is the first step of the glycolysis pathway if glycogen is the carbohydrate source and further energy is needed. If energy is not immediately needed, the glucose-6-phosphate is converted to glucose for distribution in the blood to various cells such as brain cells.

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