生物化学资料：24 The Feed Fast Cycle.pptVIP

OBJECTIVE AND REQUIREMENT 【Students Should Gain a Mastery of】 1. enzymic changes in the fed state and fasting 2. liver：nutrient distribution center 3. liver and adipose tissue in fasting 4. adipose tissue：energy storage depot 5. resting skeletal muscle in fasting 6. kidney in long-term fasting 【Students Should Gain a Familiarity with】 1. brain in fasting 2. overview of fasting I. Overview of the absorptive state Absorptive state: 2-4 hrs after a normal meal High insulin (40 μU/ml)/glucagon(80 pg/ml) ratio promotes almost all tissues use glucose as fuel during this period II. Enzymic changes in the fed state The flow of intermediates through metabolic pathways is controlled by four mechanisms: (1) the availability of substrates (2) allosteric activation and inhibition of enzymes (3) covalent modification of enzymes and (4) induction repression of enzyme synthesis. The allosteric changes usually affect the rate limiting reactions e.g. glycolysis in the liver is stimulated following a meal by increase in fructose 2, 6 – biphosphate, an allosteric activator of phosphofructokinase. I. Fructose bisphosphatase in gluconeogenesis is inhibited by fructose 2, 6-biphosphate, an inhibitor of fructose 1, 6-biphosphate. Allosteric effects work within minutes. In the fed state most of the enzymes regulated by covalent modification are in dephosphorylated state and active e.g. Pyruvate kinase, Pyruvate dehydrogenase complex, glycogen synthase, HMG – CoA reductase and acetyl –CoA carboxylase Three exceptions (active phosphorylated forms) are glycogen phosphorylase, fructose bisphosphate phosphatase and hormone-sensitive lipase of adipose tissue. Covalent modification takes minutes to hours The key enzymes are usually regulated by hormones that affect their synthesis e.g. insulin stimulates (induction) the synthesis of glucokinase, phosphofructokinase I, pyruvate kinase, the key enzyme of glycolysis, regulation of enzyme synthesis takes hours to days III. Liver：nutrie