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Chapter 4 Carbohydrates Metabolism

Chapter 4 Carbohydrates Metabolism. § 1 Overview. Carbohydrates in general are polyhydroxy aldehydes or ketones or compounds which yield these on hydrolysis. Biosignificance of Carbohydrates. The major source of carbon atoms and energy for living organisms.

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Chapter 4 Carbohydrates Metabolism

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  1. Chapter 4 Carbohydrates Metabolism

  2. § 1 Overview • Carbohydrates in general are polyhydroxy aldehydes or ketones or compounds which yield these on hydrolysis.

  3. Biosignificance of Carbohydrates • The major source of carbon atoms and energy for living organisms. • Supplying a huge array of metabolic intermediates for biosynthetic reactions. • The structural elements in cell coat or connective tissues.

  4. Glucose transporters (GLUT) • GLUT1~5 GLUT1: RBC GLUT4: adipose tissue, muscle

  5. The metabolism of glucose • glycolysis • aerobic oxidation • pentose phosphate pathway • glycogen synthesis and catabolism • gluconeogenesis

  6. glycogen Glycogenolysis Glycogenesis starch lactate Glycolysis Digestion absorption glucose aerobic oxidation Lactate, amino acids, glycerol H2O+CO2 Gluconeo-genesis Pentose phosphate pathway Ribose, NADPH

  7. §2 Glycolysis

  8. Glycolysis • The anaerobic catabolic pathway by which a molecule of glucose is broken down into two molecules of lactate. glucose →2lactic acid (lack of O2) • All of the enzymes of glycolysis locate in cytosol.

  9. G 1. The procedure of glycolysis glycolytic pathway pyruvate lactic acid

  10. 1) Glycolytic pathway : G → pyruvate including 10 reactions.

  11. G phosphorylated into glucose 6-phosphate • Phosphorylated G cannot get out of cell • Hexokinase , HK (4 isoenzymes) , glucokinase, GK in liver ; • Irreversible .

  12. Comparison of hexokinase and glucokinase hexokinase glucokinase occurrence in all tissues only in liver Km value 0.1mmol/L 10mmol/L Substrate G, fructose, glucose mannose Regulation G-6-P Insulin

  13. (2) G-6-P→ fructose 6-phosphate

  14. (3) F-6-P → fructose 1,6-bisphosphate • The second phosphorylation • phosphofructokinase-1, PFK-1

  15. (4) F-1,6-BP→ 2 Triose phosphates • Reversible

  16. (5) Triose phosphate isomerization G→2 molecule glyceraldehyde-3-phosphate, consume 2 ATP .

  17. (6) Glyceraldehyde 3-phosphate →glycerate 1,3-bisphosphate

  18. (7) 1,3-BPG→ glycerate 3-phosphate • Substrate level phosphorylation

  19. (8) Glycerate 3-phosphate → glycerate 2-phosphate

  20. (9) Glycerate 2-phosphate → phosphoenol pyruvate

  21. (10) PEP→pyruvate • Second substrate level phosphorylation • irreversible

  22. 2) Pyruvate → lactate

  23. Summary of Glycolysis

  24. Total reaction: C6H12O6 + 2ADP + 2Pi 2CH3CHOHCOOH + 2ATP + 2H2O • Formation of ATP: The net yield is 2 ~P or 2 molecules of ATP per glucose.

  25. 2. Regulation of Glycolysis • Three key enzymes catalyze irreversible reactions : Hexokinase, Phosphofructokinase & Pyruvate Kinase.

  26. 1) PFK-1 The reaction catalyzed by PFK-1is usually the rate-limiting step of the Glycolysis pathway. This enzyme is regulated by covalent modification, allosteric regulation.

  27. bifunctional enzyme

  28. 2) Pyruvate kinase • Allosteric regulation: F-1,6-BP acts as allosteric activator； ATP and Ala in liver act as allosteric inhibitors;

  29. Covalent modification: • phosphorylated by Glucagon through cAMP and PKA and inhibited.

  30. 3) Hexokinase and glucokinase • This enzyme is regulated by covalent modification, allosteric regulation and isoenzyme(同工酶) regulation. • Inhibitedby its productG-6-P. • Insulin induces synthesis of glucokinase.

  31. 3. Significance of glycolysis 1) Glycolysis is the emergency energy-yielding pathway. 2) Glycolysis is the main way to produce ATP in some tissues, even though the oxygen supply is sufficient, such as red blood cells, retina, testis, skin, medulla of kidney. • In glycolysis, 1mol G produces 2mol lactic acid and 2mol ATP.

  32. § 3 Aerobic Oxidation of Glucose

  33. The process of complete oxidation of glucose to CO2 and water with liberation of energy as the form of ATP is named aerobic oxidation. • The main pathway of G oxidation.

  34. 1. Process of aerobic oxidation

  35. 1) Oxidative decarboxylation of Pyruvate to Acetyl CoA • irreversible; • in mitochodria.

  36. Pyruvate dehydrogenase complex: E1 pyruvate dehydrogenase Es E2dihydrolipoyl transacetylase二氢硫辛酸转乙酰酶 E3 dihydrolipoyl dehydrogenase二氢硫辛酸脱氢酶 thiamine pyrophosphate, TPP (VB1) HSCoA (pantothenic acid) cofactors lipoic Acid NAD+ (Vpp) FAD (VB2)

  37. Pyruvate dehydrogenase complex: HSCoA NAD+

  38. The structure of pyruvate dehydrogenase complex

  39. HSCoA

  40. CO2 NADH +H+ NAD+ CoASH

  41. 2) Tricarboxylic acid cycle, TCAC • The cycle comprises the combination of a molecule of acetyl-CoA with oxaloacetate, resulting in the formation of a six-carbon tricarboxylic acid, citrate. There follows a series of reactions in the course of which two molecules of CO2 are released and oxaloacetate is regenerated. • Also called citrate cycle or Krebs cycle.

  42. (1) Process of reactions

  43. Citrate cycle

  44. Summary of Krebs Cycle ① Reducing equivalents

  45. ② The net reaction of the TCAC: acetylCoA+3NAD++FAD+GDP+Pi+2H2O → 2CO2+3NADH+3H++FADH2+GTP+ HSCoA ③ Irreversible and aerobic reaction ④ The enzymes are located in the mitochondrial matrix.

  46. ⑤ Anaplerotic reaction of oxaloacetate

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