生物化学

1. 生物化学 Chapter 3 Metabolism of Carbohydrate

4. Section 1 Digestion and uptaking of carbohydrate 第一节 糖的消化与吸收

5. 1.1 糖类水解酶 a-淀粉酶 b-淀粉酶 淀粉酶 葡萄糖淀粉酶 纤维素酶 多糖水解酶 异淀粉酶 半纤维素酶 果胶酶 麦芽糖酶 蔗糖酶 糖苷水解酶 乳糖酶 ●●●

6. 1.2 糖类在人体中的消化 糖类食物 唾液淀粉酶 咀嚼、部分水解 第一阶段 有限水解 HCl 胰淀粉酶 a-糊精、麦芽糖和少量葡萄糖 第二阶段 单糖 糖苷酶 吸收

7. 1.3 糖的吸收 糖的吸收就是指游离的葡萄糖（单糖）进入到生物体内（细胞内）的过程。 主动运输 促进扩散 糖的吸收方式 基团转位

8. 血糖的来源、去向 血糖 80－120 mg/100 ml 40－70， 120－180 低 高 • Glucose is very soluble source of quick and ready energy. • It is a relatively stable and easily transported. • Glucose is the only source of energy in red blood cells

9. Section 2 Catabolism of monocarbohydrate 第二节 单糖的分解代谢 Glycolysis and Gluconeogenesis Glycolysis- Derived from the Greek stem glyk-,”sweet”, and the word lysis, “dissolution”.

10. 2.1 Concepts 酵解（glycolysis):是酶将葡萄糖降解成丙酮酸并伴随着生成ATP的过程。它是动物、植物、微生物细胞中葡萄糖分解产生能量的共同代谢途径。 发酵（fermentation)：厌氧有机体把酵解生成的NADH中的氢交给丙酮酸，生成乳酸；或丙酮酸脱羧生成的乙醛，生成乙醇。 发酵类型（types of fermentation)。 呼吸（respiration）

11. Glycolysis The cell is the functional unit of organisms. All metabolic activity is based on cells

12. 2.2 Glycolysis and the Catabolism of Hexoses—— EMP pathway 2.2.1 The Elucidation of Glucose Degradation Pathway Has a Rich History Embden-Meyerhof-Parnas pathway • 1890s, Buchner (Germany), fermentation occurred outside living yeast cells (the “sucrose surprise”): metabolism became chemistry; The Nobel Prize in Chemistry 1907 for his biochemical researches and his discovery of cell-free fermentation

13. 2.2.1 The Elucidation of Glucose Degradation Pathway Has a Rich History • 1910s to 30s, Embdenand Meyerhof (Germany), glycolysis in muscle and its extracts: in vitro reconstruction from glycogen to lactic acid; many reactions of lactic acid (muscle) and alcohol (yeast) fermentations are the same; lactic acid is reconverted to carbohydrate in the presence of O2; some phosphorylated compounds are energy-rich. • “Embden-Meyerhof pathway”. The Nobel Prize in Physiology or Medicine 1922 for his discovery of the fixed relationship between the consumption of oxygen and the metabolism of lactic acid in the muscle 梅耶霍夫 Otto Meyerhof

14. 2.2.1 The Elucidation of Glucose Degradation Pathway Has a Rich History • 1940s, Lipmann, discovery of Coenzyme A and acetyl-CoA; • 1930s to 40s, Carl Cori and Gerty Cori, discovery of glycogen phosphorylase (磷酸化酶）and glucose-1-phosphate; • 1940s, Cori, Cori and Houssay, discovery of hormone （激素） regulation of metabolism; • The whole pathway of glycolysis (Glucose to pyruvate) was elucidated by the 1940s.

15. 2.2.2 Overview of glycolysis糖酵解概况 • The glycolysis is a pathway from glucose to pyruvate; Yeast 葡萄糖 丙酮酸 Exercising muscle The fate of glucose is varies with physiological conditions, tissues, and organisms. Aerobic conditions Anaerobic conditions

16. 2.2.2 Overview of glycolysis糖酵解概况 2. Glycolysis can occurs under anaerobic conditions(fermentations); Fermentations provide usable energy in t absence of oxygen. 3. glycolysis takes place in cytoplasma （细胞质）； Glucose is an important fuel for most organisms

17. 2.2.2 Overview of glycolysis 4. The glycolysis pathway consists of two phases Preparatary phase (耗能) 2ATP Payoff phase (产能)2×2 ATP Net: 2 ATP； a limited amount

18. 2.2.2 Overview of glycolysis 碳原子途径 磷酸途径 氧化还原反应的电子途径 5. Intermediary metabolites are phosphated（磷酸化的）; 6. Three types of chemical changes； 7. Glycolysis is highly regulated. Glycolysis is an energy-conversion pathway in many organisms

19. 2.2.2 Overview of glycolysis Glucose is phosphorylated. The negative charge concentrates glucose in the cell and glucose becomes less stable. (P，C ，e )

20. 2.2.2 Overview of glycolysis 8. Types of reactions occurring in glycolysis Phosphoryl group transfer: kinase(激酶); 激酶 磷酸化酶

21. 2.2.2 Overview of glycolysis 8. Types of reactions occurring in glycolysis Phosphoryl group shift: mutase（变位酶） Phosphoryl shift. A phosphoryl group is shifted from one oxygen atom to another within a molecule by a mutase.

22. 2.2.2 Overview of glycolysis 8. Types of reactions occurring in glycolysis Isomerization:isomerase(异构酶); Isomerization. A ketose (酮糖） is converted into an aldose （醛醣）, or vice versa, by an isomerase.

23. 2.2.2 Overview of glycolysis 8. Types of reactions occurring in glycolysis Dehydration: dehydratase（enolase, 烯醇化酶） Dehydration. A molecule of water is eliminated by a dehydratase.

24. 2.2.2 Overview of glycolysis 8. Types of reactions occurring in glycolysis Aldol cleavage: aldolase（醛缩酶） Aldol cleavage. A carbon-carbon bond is split in a reversal of an aldol condensation by an aldolase.

25. 2.2.2 Overview of glycolysis • Phosphoryl group transfer: kinase; • Phosphoryl group shift: mutase（变位酶）; • Isomerization: isomerase; • Dehydrogenation: dehydrogenase（脱氢酶）; • Dehydration: dehydratase (enolase，烯醇化酶); • Aldol cleavage: aldolase（醛缩酶）.

26. Preparatory phase: Phosphorylation of glucose and its conversion to glyceraldehyde-3-phosphate Payoff phase Conversion of glyceraldehyde-3-phosphate to pyruvate and the coupled formation of ATP

27. 2.2.3 The reactions of glycolysis 葡萄糖 葡萄糖-6-磷酸 果糖-6-磷酸 果糖-1,6-二磷酸 甘油醛-3-磷酸 二羟丙酮磷酸

28. 二羟丙酮磷酸 甘油醛-3-磷酸 1,3-二磷酸甘油酸 3-磷酸甘油酸 2-磷酸甘油酸 磷酸烯醇式丙酮酸 丙酮酸

29. Intermediary metabolites are phosphated （磷酸化的） Hexokinase traps glucose in the cell and begins glycolysis • 带有负电荷的磷酸基团使中间产物具有极性，从而使这些产物不易透过脂膜而失散。 • 磷酸基团在各反应步骤中，对酶来说，起到信号基团的作用，有利于与酶结合而被催化。 • 磷酸基团经酵解作用后，最终形成ATP的末端磷酸基团，因此具有保存能量的作用。

30. Stage of glycolysis • The glycolytic pathway can be divided into three stages: • 1)Glucose is trapped and destabilized. • 2)Two interconvertible three-carbon molecules are generated by cleavage of six-carbon fructose. • 3)ATP is generated. • Stage 1 of Glycolysis. The three steps of stage 1begin with the phosphorylation of glucose by hexokinase

31. (1) Glucose is Phosphorylated First to Enter Glycolysis Hexokinase 己糖激酶 ΔG°’= -4.0 kcal mol-1 Phosphoryl transfer reaction. Kinases transfer phosphate from ATP to an acceptor. Hexokinase has a more general specificity in that it can transfer phosphate to other sugars such as mannose（甘露糖）.

32. (1) Glucose is Phosphorylated First to Enter Glycolysis ATP与葡萄糖的反应机制 Mg2+-ATP复合物 ( Mg2+-ATP complex)

33. (1) Glucose is Phosphorylated First to Enter Glycolysis 己糖激酶与葡萄糖结合时的构象变化 Induced fit in hexokinase. As shown in blue, the two lobes of hexokinase are separated in the absence of glucose. The conformation of hexokinase changes markedly on binding glucose, as shown in red. The two lobes of the enzyme come together and surround the substrate.

34. (1) Glucose is Phosphorylated First to Enter Glycolysis 1、己糖激酶是一种调节酶，产物葡萄糖-6-磷酸和ADP能使该酶受到变构抑制。但葡萄糖磷酸激酶却不受葡萄糖-6-磷酸的抑制。 2、葡萄糖激酶的对葡萄糖的米氏常数Km (5~10mmol/L) 比己糖激酶的Km值 （0.1mmol/L）大得多，因此，当葡萄糖浓度相当高时，葡萄糖激酶才起作用。

35. 动物己糖激酶同工酶的性质比较

36. (2) Glucose-6-P Isomerizes from an Aldose to a Ketose Phosphoglucose Isomerase 磷酸葡萄糖同分异构酶 ΔG°’= 0.40 kcal/mol The conversion of an aldose（醛糖） to a ketose（酮糖）. • 先开环异构化闭环 • 受6-磷酸-葡萄糖酸抑制（在酸性条件下）

37. (2) Glucose-6-P Isomerizes from an Aldose to a Ketose Phosphoglucose Isomerase The enzyme opens the ring, catalyzes the isomerization, and promotes the closure of the five member ring.

38. (3) Fructose-6-P is Further Activated by Phosphorylation Phosphofructokinase PFK（磷酸果糖激酶） The 2nd investment of an ATP in glycolysis. ΔG°’= -3.4 kcal mol-1 Bismeans two phosphate groups on two different carbon atoms. Dimeans two phosphate groups linked together on the same carbon atom. PFK is an important allosteric enzyme（别构酶） regulating the rate of glucose catabolism and plays a role in integrating metabolism.

39. (3) Fructose-6-P is Further Activated by Phosphorylation 磷酸果糖激酶是一种变构酶，糖酵解的速率严格地依赖该酶的活力水平，它是哺乳动物糖酵解途径最重要的调控关键酶。 肝中PFK受高浓度的ATP的抑制。ATP结合于调节部位。ATP对该酶的别构抑制效应可被AMP解除。因此ATP/AMP的比例关系对此酶有明显的调节作用。

40. Effectors of phosphofructokinase （PFK） 柠檬酸 磷酸肌酸

41. (4) Fructose-1,6-Bisphosphate is Cleaved (lysed) in the Middle Aldolase (醛缩酶） 1 4 3 ΔG°’= 5.7 kcal mol-1 Reverse aldol condensation; converts a 6 carbon atom sugar to 2 molecules, each containing 3 carbon atoms.

42. Stage 2 of glycolysis 果糖-1，6-二磷酸 FBP 二羟丙酮磷酸 （DHAP） 甘油醛-3-磷酸 （GAP）

43. (5) Triose phosphate Interconvert Triose phosphate isomerase 丙糖磷酸异构酶 ，TIM ΔG°’ = 1.8 kcal mol-1 二羟丙酮磷酸 （DHAP） 甘油醛-3-磷酸 （GAP）

44. (5) Triose phosphate Interconvert 甘油醛-3-磷酸

45. (5) Triose phosphate Interconvert 单烯二羟负 离子中间体 二羟丙酮磷酸 （DHAP） 甘油醛-3-磷酸 （GAP） ΔG°’ = 1.8 kcal mol-1 All the DHAP is converted to glyceraldehyde 3-phosphate（GAP）. Although, the reaction is reversible it is shifted to the right since glyceraldehyde 3-phosphate is a substrate for the next reactions of glycolysis. Thus, both 3-carbon fragments are subsequently oxidized. This structural motif, called an TIM barrel, is also found in others glycolytic enzymes. His 95 and Glu 165 located in the barrel is active site .

46. Catalytic mechanism of triose phosphate isomerase

47. Stage 3 of glcolysis: the oxidation of three-carbon fragments yields ATP -CH2 -C-OH -C=O -COOH

48. (6) Glyceraldehyde-3-phosphate is Oxidized The energy yielding phase Glyceraldehyde 3-phosphate DH 甘油醛-3-磷酸脱氢酶，GAPDH 1，3二磷酸甘油酸 ΔG°’ = 1.5 kcal mol-1 An aldehyde（醛）is oxidized to carboxylic acid（羧酸） and inorganic phosphate is transferred to form acyl-phosphate（酰基磷酸）. NAD+ is reduced to NADH. 1,3-BPG has a high phosphoryl-transfer potential. It is a mixed anhydride（酐）. Notice, under anaerobic conditions NAD+ must be re-supplied.

49. (6) Glyceraldehyde-3-phosphate is Oxidized 1，3二磷酸甘油酸 GAPDH反应机制 ~ 甘油醛-3-磷酸 ∆G0’ = - 43.1 kJ/mol ∆G0’ = 49.4 kJ/mol

50. (6) Glyceraldehyde-3-phosphate is Oxidized 甘油醛-3-磷酸脱氢酶 The active site includes a Cys and His adjacent to a bound NAD+ 无活性的酶 GAPDH 碘乙酸