Chapter 4 Carbohydrates

1. Chapter 4 Carbohydrates Objectives: • Learn the major sources of dietary carbohydrates. • What are these digested to and absorbed as? • What are the major types of glucose transporters and where are they found? How are these transporters regulated? • Understand how the major carbohydrates are utilized metabolically by your cells • Understand the basic processes involved in glycolysis, glycogenesis, glycogenolysis, gluconeogenesis, and the hexosemonophosphate shunt • Understand how fructose and galactose enter these pathways • Learn how these pathways are regulated by insulin and glucagon • What are the major ways that regulation takes place (mechanisms of regulation)? • Learn how ethanol consumption impacts the metabolic pathways for carbohydrates • Acetaldehyde toxicity • High NADH:NAD+ ratio • Substrate competition • Induced metabolic tolerance • Learn how some diseases are associated with carbohydrate metabolism • Diabetes • Hypoglycemia

2. Enzymes involved in carbohydrate digestion and metabolism are stereospecific for D sugars Reference molecule Chiral carbon? Anomeric carbon? Fig. 4-2, p. 74

3. Pentoses? Reducing sugars? Oligosaccharides? Table 4-1, p. 75

4. Fig. 4-5a, p. 77

5. r Fig. 4-6, p. 78

6. Table 4-2, p. 81

7. Golgi Apparatus Glucose Transport Vesicle-bound transporters Synthesized transporters from ribosomes Translocation Signal? Insulin Insulin receptor Fig. 4-8, p. 82

9. (a) Glucose (reference food) (b) Low glycemic index (c) Fasting baseline Blood glucose (mg/dL) Hours Glucose meal Fig. 4-9, p. 83

11. Fig. 4-10, p. 84

12. Fig. 4-11a, p. 85

13. Glycogen synthase – active when dephosphorylated, inactive when phosphorylated; insulin vs. glucagon Fig. 4-11b, p. 85

14. Glycogenolysis – activated by glucagon and epinephrine through action on glycogen phosphorylase (phosphorylase a, phosphorylated – active; phosphorylase b, dephosphorylated - inactive Fig. 4-12, p. 86

15. Fig. 4-13, p. 87

17. Fig. 4-14, p. 88

18. Citrate synthase • Aconitase • Isocitrate dehydrogenase • a ketoglutarate dehydrogenase • Succinyl thiokinase • Succinate dehydrogenase • Fumarase • Malate dehydrogenase Fig. 4-15, p. 91

19. Fig. 4-16, p. 91

20. Fig. 4-17, p. 93

21. Used when nucleic acids are needed Used when NADPH is needed Fig. 4-19, p. 95

22. Brain, neurons, and RBCs are dependent on glucose as a nutrient. When dietary intake of glucose is decreased and glycogen stores are depleted, we can make new glucose from alternative fuel sources in a process called gluconeogenesis • Fuels used to make new glucose include • amino acids, • lactate, • Glycerol • Organ which most often performs gluconeogenesis is the liver

23. Irreversible rxn Fig. 4-21, p. 97

24. Four Mechanisms for Regulating Blood Glucose • Allosteric modulation by compounds within the pathways • Hormonal activation of covalent modification of specific enzymes • Directional shifts in reversible reactions by changes in reactant or product concentrations • Translocation of enzymes within the cell

25. Citrate synthase • Aconitase • Isocitrate dehydrogenase • a ketoglutarate dehydrogenase • Succinyl thiokinase • Succinate dehydrogenase • Fumarase • Malate dehydrogenase Regulated by NADH/NAD+ Regulated by ATP/ADP Fig. 4-15, p. 91

28. Fig. 4-22, p. 101

29. Ethyl Alcohol: Metabolic Impact • Ethyl alcohol most closely resembles a carbohydrate • It has caloric value, and is a common dietary component of alcoholic beverages • Each gram of alcohol yields 7kcal of energy • May account for 10% of total energy intake in moderate consumers • May account for 50% of total energy intake in alcoholics. • Ethanol is absorbed throughout the digestive tract and is transported in the blood. • It is then oxidatively degraded, mostly in the liver, to acetaldehyde and then to acetate. Acetate eventually is converted to acetylcoA • Alcohol dehydrogenase • MEOS or cytochrome P-450 • catalase

30. ethanol + NAD+ ----> acetaldehyde + NADH Acetaldehyde is toxic reactive with amino groups and may interact with proteins competes for the plasma carrier of pyridoxal (vitamin B6) acetaldehyde + NAD+ ----> acetic acid + NADH Acetic acid can lead to acidosis Because the two reactions require NAD+, NADH can build up. What problems might this cause? anaerobic metabolism to regenerate NAD+ lack of pyruvate for gluconeogenesis - hypoglycemia

31. Fig. 4-23, p. 102

32. Metabolic consequences • Acetaldehyde toxicity • Elevated NADH:NAD+ ratio • Metabolic competition • Induced metabolic tolerance • Elevates HDL in serum and lowers serum lipoproteins • Slowing development of smooth muscles in atherosclerosis

33. Diseases of Carbohydrate Metabolism • Diabetes • Hypoglycemia