講義案例生化下ch14

1、CHAPTER 14Glycolysis, Gluconeogenesis, and the Pentose Phosphate PathwayHistory1856年，法國的Louis Paster(巴斯德)證實發(fā)酵是由微生物進行的。這是科學史上的一塊里程碑。但在那時，認為葡萄糖到乙醇的發(fā)酵過于復雜，無法在活細胞外重復這一過程。1896年，德國科學家Hans Buchner (older brother)和Eduard Buchner（畢希納）發(fā)現(xiàn)發(fā)酵可在無細胞條件下進行。1905年，Harden和Young發(fā)現(xiàn)將無機磷酸加入酵母抽提物后，可以激活和延長葡萄糖發(fā)酵。在發(fā)酵過程中，無機磷酸從反

2、應培養(yǎng)基中消逝。他們認為發(fā)酵是通過形成一個或多個糖磷酸酯進行工作的。1930年前后，德國的Embden和Meyerhof等將發(fā)酵中每一步反應加以分離，鑒定了導致葡萄糖到丙酮酸的10步反應。Saccharomyces cerevisiae is a species of budding yeast Paster (1822-1895)The father of microbiology Eduard Buchner (May 20, 1860 August 13, 1917) was a German chemist and zymologist, the winner of the 1907

3、Nobel Prize in Chemistry “for his biochemical researches and discovery of cell-free fermentation” .Buchner Definition glykys-, sweet or sugar；lysis,spliting The pathway by which glucose is converted to lactate in muscle The anaerobic catabolic pathway by which a molecule of glucose is broken down in

4、to two molecules of pyruvate. Embden-Meyerhof-Pathway, EMP (埃姆登-邁耶霍夫途徑) GermanyThe two phases of glycolysisATP and NADP formation Coupled to Glycolysis C6H12O6 + 2NAD+ 2H3C-CO-COO- + 2NADH+2H+ Go = -146 KJ/mol 2ADP + 2Pi 2ATP + 2H2O Go = 2 x 30.5 = 61.0 KJ/mol C6H12O6 + 2ADP + 2Pi + 2NAD+ 2 pyruvate

5、 + 2ATP +2NADH + 2H+ Go = -146 + 61 = -85 KJ/mol under standard-state conditions: (61/146) 100% = 41.7% 大部分汽油機僅僅在30%左右 Three possible catabolic fates of the pyruvate formed in glycolysis 1. Because the plasma membrane generally lacks transporters for phosphorylated sugar，the phosphorylated glycolyti

6、c intermediates cannot leave the cell.2. Phosphoryl groups are essential components in the enzymatic conservation of metobolic energy.3. Binding energy resulting from the binding of phosphate groups to the active sites of enzymes lowers the activation energy and increases the specificity of the enzy

7、matic reactions Importance of phosphorylated intermediates Phosphorylation of glucose by ATP creates a charged molecule that cannot easily cross the plasma membrane. Hexokinase: Km = 0.1mM blood glucose 4-5mM allosterical inhibitor : G-6-P isozymes: HK1,2,3,4 Glucokinase (HK4): Km = 10.0 mM not prod

8、uct- inhibited Glucose-6-phosphate is the branch point for several carbohydrate metabolic pathways.When glucose levels are low, hexokinase is responsible for phosphorylating glucose for glycolysis;When glucose levels are high, glucokinase phosphorylates glucose for storage as glycogen.Insulin glucok

9、inase diabetes mellitusHarden-Young esterThe first committed step A. ATP is an allosteric inhibitorRegulation of phosphofructokinase 1B. AMP reverses the inhibition induced by ATP. ATP concentration varies a little, while AMP concentration varies a lot, so the rate of glycolysis varies a lot. C. Cit

10、rate is another allosteric inhibitor of phosphofructokinase. Inhibition of glycolysis by citrate ensures that, if the citric acid cycle is already saturated, there is no need for glucose to “ feed ” the citric acid cycle. D. - D- fructose-2,6-bisphosphate is an allosteric activator for phosphofrucokinase-1. Negative feedback 1. Increase the affinity of kinase for subs