又名磷酸己糖支路或6-磷酸葡萄糖酸途径发生在细胞液.ppt

5 6 9 10 Regulation of Hexokinase Hexokinase reaction is metabolically irreversible G6P (product) levels increase when?glycolysis is inhibited at sites further along in the pathway G6P inhibits hexokinase isozymes I, II and III that are active at normal glucose concentrations (Km values ~10-6 to 10-4M) Glucokinase (hexokinase IV, Km ~10-2M) forms G6P in the liver (for glycogen synthesis) when glucose is abundant (activity is modulated by fructose phosphates and a regulatory protein) 1. When ATP levels are sufficient, glycolysis activity decreases Hexokinase inhibited by excess glucose 6-phosphate PFK-1 is inhibited by ATP and citrate Pyruvate kinase is inhibited by ATP 2. When ATP is needed, glycolysis is activated AMP (the product of ATP consumption) relieve the inhibition of PFK-1 by ATP Fructose 2,6-bisphosphate (F2,6BP) relieve the inhibition of PFK-1 by ATP Pyruvate kinase is activated by F1,6BP Step 1 Step 3 Step 10 Regulation of the TCA cycle TCA cycle的调节位点在三个不可逆的步骤： 1. 柠檬酸合酶：受ATP、柠檬酸、琥珀酰CoA、 脂酰CoA抑制。 2. 异柠檬酸脱氢酶：受ATP、NADH抑制，受 ADP激活。 3. ?-酮戊二酸脱氢酶：受NADH、琥珀酰CoA 抑制。 此外，由于细胞中草酰乙酸浓度较低，其 浓度是决定TCA cycle速度的重要因素之一。 4. 丙酮酸脱氢酶系的调节控制 （1）产物抑制 乙酰CoA抑制E2，NADH抑制E3。 （2）核苷酸的反馈抑制 即细胞能量状态（能荷）的控制 （3）共价修饰的调节 可逆磷酸化作用（酶丝氨酸羟基上） E1受到两个调节酶控制： a. 丙酮酸脱氢酶激酶，ATP为磷酸供体，磷酸 化的酶为inactive形式 b. 丙酮酸脱氢酶磷酸（酯）酶：催化脱氢酶去 磷酸，为active形式 The Pasteur Effect Under anaerobic conditions the conversion of glucose to pyruvate is much higher than under aerobic conditions (yeast cells produce more ethanol and muscle cells accumulate lactate) The Pasteur Effect is the slowing of glycolysis in the presence of oxygen More ATP is produced under aerobic conditions than under anaerobic conditions, therefore less glucose is consumed aerobically 酵解、TCA cycle及氧化磷酸化途径间的协调控制 巴斯德效应：巴斯德发现在进行旺盛无氧酵解的酵母中 通入氧气，葡萄糖消耗减少，乳酸堆积迅速下降。说明糖的有 氧氧化对酵解产生抑制作用。 原因：有氧条件下 （1）酵解产生的NADH进入氧化磷酸化，将H传递给氧，并 产生大量ATP。 （2）丙酮酸进入TCA cycle，乳酸自然减少，经TCA Cycle 也产生大量ATP，同时柠檬酸浓度增加。 高浓度的ATP和柠檬酸进入胞液后，抑制PFK活性