生物化学原理教学（杨荣武）Chapter22 Glycolysis.pptVIP

Outline Overview of Glycolysis All glycolysis reactions Fates of NADH and Pyruvate In the presence of O2 In the absence of O2 How other substances other than glucose enter the glycolysis Physiological function of glycolysis Regulation of glycolysis The Embden-Meyerhof (Warburg) Pathway Essentially occurring in all cells Cellular location: cytosol Ten reactions - same in all cells - but rates differ Two phases: 1st phase- investing phase: glucose →F-1,6-2P →2G-3-P 2nd phase-harvesting phase: produces two pyruvates, ATPs and NADH Three possible fates for pyruvate Don’t panic! All you have to memorize are the total reaction, three rate-limiting reactions, three inhibitors, two substrate-level phosphorylation steps and major regulation mechanisms. First Phase of Glycolysis The first reaction - phosphorylation of glucose Hexokinase or glucokinase This is a priming reaction - ATP is consumed here in order to get more later ATP makes the phosphorylation of glucose spontaneous 1st step in glycolysis; ?G large, negative Catalyzed by Hexokinase or glucokinase First irreversible reaction Hexokinase (and glucokinase) act to phosphorylate glucose and keep it in the cell Km for glucose is 0.1 mM; cell has 4 mM glucose So hexokinase is normally active! Glucokinase (Kmglucose = 10 mM) only turns on when cell is rich in glucose Hexokinase is regulated - allosterically inhibited by (product) glucose-6-P Binding of glucose to Hexokinase induces a large conformational change This same change in conformation is observed for ALL kinases! It also accounts for the fact that water cannot be used for hydrolysis of ATP unless we fool the enzyme by using xylose instead of glucose. Glucose-6-P to Fructose-6-P Catalyzed by Phosphoglucoisomerase Why does this reaction occur?? next step (phosphorylation at C-1) would be tough for hemiacetal -OH, but easy for primary -OH isomerization activates C-3 for cleavage in aldolase reaction Ene-diol intermediate in this reaction A mo