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Chapter 4 Carbohydrate Metabolism

Chapter 4 Carbohydrate Metabolism. 糖代谢. Dept Biochem: Xiaoli Zheng. Section 1 Overview. 1.1 Cells have choice among alternative substrates, but glucose is more important for their needs. The human body is a mechine fueled by food. Carbohydrate Triglyceride Protein Alcohol. food.

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Chapter 4 Carbohydrate Metabolism

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  1. Chapter 4 Carbohydrate Metabolism 糖代谢 Dept Biochem: Xiaoli Zheng

  2. Section 1 Overview

  3. 1.1 Cells have choice among alternative substrates, but glucose is more important for their needs. The human body is a mechine fueled by food. Carbohydrate Triglyceride Protein Alcohol food CO2 + H2O

  4. Most cells have choice among alternative substrates, including glucose,fatty acids, andamino acids. • Others are more specialized, a few cell types, such as neurons and red blood cells, depend mainly or exclusively on glucose for their energy needs.

  5. Most important functions of carbohydrates ： (1) Generation of metabolic energy by the catabolism of glucose. (2) Maintenance of a normal blood glucose level. Glucose is required at all times. In the fasting state, the liver has to provide glucose by the degradation of stored glycogen or by synthesis from noncarbohydrates.

  6. ③Supply of specialized monosaccharides as biosynthetic precursors. ribose: the synthesis of nucleotides and nucleic acid; amino sugars and acidic sugar derivatives: the synthesis of glycolipids, proteglycans, and glycoproteins (play roles in many biological processes, such as signal transduction, immunity, and molecular recognition) ④Some sugar derivates are important bioactive compound, such as NAD+,FAD, and ATP.

  7. 1.2 Glucose is the principal transported carbohydrate in humans Carbohydrates are widely distributed in plants and animals. Glucose is the most abundant monosaccharide in dietary carbohydrates.

  8. Carbohydrates are aldehyde or ketone derivatives of polyhydric alcohols. • Monosaccharide: cannot be hydrolyzed into simpler carbohydrates . trioses,tetroses,pentoses,hexoses or heptoses • Oligosaccharide: are condensation products of two to ten monosaccharide. maltotriose • Polysaccharide： are condensation products of more than ten monosaccharide • Glycoconjugate

  9. glucose fructose monosaccharide

  10. galactose ribose

  11. maltose glucose + glucose sucrose glucose + fructose lactose glucose + galactose oligosaccharide

  12. Starch Glycogen Cellulose polysaccharide

  13. α-1,6 glycosidic bonds α-1,4 glycosidic bonds 淀粉的分子结构(structure of starch)

  14. α-1,6 glycosidic bonds α-1,4 glycosidic bonds 糖原的分子结构(structure of glycogen)

  15. β-1,4 glycosidic bonds 纤维素的分子结构(structure of cellulose)

  16. Being small, soluble, and osmotically active, glucose can be transported by the blood, but it can not be stored in the cells. For storage, it has to be converted to the polysaccharide glycogen.

  17. A group of diseases characterized by high level of blood glucose resulting from defects ininsulin production, insulin action, or both. Blood sugar = Blood glucose 4.0 nmol /L---5.5 nmol /L Diabetes

  18. 1.3 Glucose uptake into the cell is regulated. Glucose is water soluble to penetrate membranes by passive diffusion. To enter the cell, it requires specialized carriers in the plasma membrane.

  19. liver pancreas stomach glucose Glucose metabolism pancreas insulin

  20. Insulinis a small protein consisting of an A chain of 21 amino acids linked by two disulfide (S-S) bridges to a B chain of 30 amino acids.

  21. Insulin signal transduction glucose Glucose transporter Golgi P - - P insulin receptor Insulin

  22. ""key" and “door"

  23. Type 2 Diabetes - after 40 years - cells ignore the insulin - insulin independence Type 1 Diabetes -children and young adults - cells that produce insulin are destroyed - insulin dependence No insulin Insulin resistance

  24. Glycogenolysis Glycogenesis aerobic Glycolysis Pentose Phosphate Pathway anaerobic Gluconeogenesis Digestion and Ingestion Digestion and Ingestion 1.4 Glucose oxidation can proceed in many different pathways. glycogen Ribulose-5 -phosphate + NADPH+H+ H2O andCO2 glucose pyruvate lactate lactate 、amino、glycerol starch

  25. Section 2 Glycolysis

  26. 2.1 Glycolysis, the major pathway for glucose metabolism. Glycolysis takes place in the cytosol of all cells。 Glycolysis can be carried out in the absence of oxygen ( anaerobically) and produce lactate. During glycolysis ,glucose is converted to two molecules of lactate, and two molecules of ATP per molecule of glucose oxidized.

  27. The reaction process of Glycolysis could be separated into two phases. Glycolytic Pathway Lactate production The overall equation for glycolysis from glucose to lactate is as follows: Glucose+2ATP+2Pi→2L(+)-Lactate+2ATP+2H2O

  28. glucose fructose-1,6-bisphosphate glycolysis glyceraldehyde-3-phosphate pyruvate lactate activation lysis Glycolytic Pathway releasing energy reduction Lactate Production

  29. a. activation (1) Glucose is converted to two molecules of pyruvate glucose→fructose-1,6-bisphosphate(F-1,6-BP，FDP）

  30. * hexokinase ATP (1) ADP glucose-6-phosphate glucose Phosphohexose isomerase (2) * phosphofructokinase ADP ATP (3) fructose-1,6-bisphosphate fructose-6-phosphate activation committed step

  31. dihydroxyacetone phosphate (4) triose phosphate isomerase (5) aldolase fructose-1,6-bisphosphate glyceraldehyde-3-phosphate b、Cleavage

  32. NAD++Pi NADH+H+ (6) glyceraldehyde3-phosphate dehydrogenase glycerate-1,3-diphosphate glyceraldehyde-3-phosphate ADP Phosphoglycerate kinase (7) ATP (8) Phosphoglycerate mutase glycerate-2-phosphate glycerate-3-phosphate c. releasing energy Substrate-level phosphorylation

  33. H2O ⑼ enolase glycerate-2-phosphate phosphoenolpyruvate ADP * ⑽ Pyruvate kinase ATP pyruvate Substrate-level phosphorylation

  34. lactate pyruvate NADH+H+ NAD+ ⑾ Lactate dehydrogenase (2) Lactate Production Under anaerobic conditions, pyruvate is reduced by the NADH to lactate.

  35. GLYCOLYSIS

  36. Glycolysis can be carried out in the absence of oxygen ( anaerobically) and produce lactate. During glycolysis ,glucose is converted to two molecules of lactate, and two molecules of ATP per molecule of glucose oxidized.

  37. * hexokinase G-6-P ATP (1) ADP glucose-6-phosphate - glucose 2.2 Glycolysis could be regulated by changes of three key enzymes’ activities.(1) hexokinase Negative feedback 己糖激酶 hexokinase

  38. ADP、AMP insulin + ATP Citrate Low pH glucagon - (2) 6-phosphofructokinase-1 （PFK）： Phosphofructokinase is the most important regulatory enzyme 6-phosphofructokinase-1

  39. * phosphofructokinase ADP ATP (3) fructose-1,6-bisphosphate Positive feedback fructose-6-phosphate

  40. ATP Alanine (liver) F-1,6-BP + - 3. pyruvate kinase： pyruvate kinase Negative feedback

  41. 2.3 Physiological Significances of Glycolysis 1. Mature erthrocytes have no mitochondric. They do not engage in biosynthetic activity and require ATP only for the maintenance of ion gradients across their membrane. Their energy requirement is so modest that it can be met by the anaerobic glycolysis of 15 to 20g of glucose per day.

  42. 2. Skeketal muscle has to increase its ATP production more than 20-fold during bouts or vigorous contraction during a 100-m sprint, for example, the supply of oxygen by the blood becomes a limiting factor. To keep going, the muscles must turn glucose from the blood and their own stored glycogen into lactic acid.They lactate concentration in the blood rise 5- to 10-fold in this situation. 3. Ischemic tissues, which have been cut off from their blood supply, use anaerobic glycolysis for crisis management.

  43. Thank you!

  44. Section 3 Aerobic Oxidation of Carbohydrates

  45. 重要概念：aerobic oxidation of glucose • Aerobic conditions, glucose is completely oxidazed to CO2 and H2O,linked to the formation of ATP , the whole process is referred to as aerobic oxidation of glucose. • Aerobic oxidation of carbohydrates takes place in the cytoplasm and mitochondrion of cells。 • glucose is converted 36/38 molecules of ATP per molecule of glucose oxidized.

  46. G（Gn） cytoplasm pyruvate Acetyl-CoA mitochondrion TCA [O] CO2 NADH+H+ FADH2 H2O ATP ADP 一、有氧氧化的反应过程Reaction Process of Aerobic Oxidation

  47. （一）Production of Pyruvate by Glycolytic Pathway： • During Glycolytic Pathway, in cytoplasm, glucose is converted to two molecules of pyruvate, and two molecules of ATP, and two molecules of NADH+H+ per molecule of glucose oxidized.

  48. * Pyruvate dehydrogenase pyruvate acetyl CoA NAD+ +HSCoA NADH+H+ +CO2 （二）Production of Acetyl-CoA by Oxidative Decarboxylation of Pyruvate： 丙酮酸的氧化脱羧作用

  49. In aerobic oxidation,after pyruvate is produced, it diffuses through the process in the outer motochondria membrane and is transported across the inner motochondria membrane . In the motochondrial matrix, it is oxidatively decarboxylated to acetyl-CoA. • This irreversible reaction is catalyzed by pyruvate dehydrogenase, a multienzyme complex with three components

  50. During this reaction, in mitochondrion, glucose is converted to two molecules of acetyl-CoA, and two molecules of CO2, and two molecules of NADH+H+ per molecule （2×3 = 6 ATP）. • Key enzyme: pyruvate dehydrogenase complex

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