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Lecture Biochemistry (2/e): Chapter 19 - Reginald Garrett, Charles Grisham

Glycolysis is a paradigm of metabolic pathways. Carried out in the cytosol of cells, it is basically an anaerobic process; its principal steps occur with no requirement for oxygen. Living things first appeared in an environment lacking O2, and glycolysis was an early and important pathway for extracting energy from nutrient molecules. It played a central role in anaerobic metabolic processes during the first 2 billion years of biological evolution on earth. | Chapter 19 Glycolysis to accompany Biochemistry, 2/e by Reginald Garrett and Charles Grisham All rights reserved. Requests for permission to make copies of any part of the work should be mailed to: Permissions Department, Harcourt Brace & Company, 6277 Sea Harbor Drive, Orlando, Florida 32887-6777 Outline 19.1 Overview of Glycolysis 19.2 Coupled Reactions in Glycolysis 19.3 First Phase of Glycolysis 19.4 Second Phase of Glycolysis 19.5 Metabolic Fates of NADH and Pyruvate 19.6 Anaerobic Pathways for Pyruvate 19.7 Energetic Elegance of Glycolysis 19.8 Other Substrates in Glycolysis Overview of Glycolysis The Embden-Meyerhof (Warburg) Pathway Essentially all cells carry out glycolysis Ten reactions - same in all cells - but rates differ Two phases: First phase converts glucose to two G-3-P Second phase produces two pyruvates Products are pyruvate, ATP and NADH Three possible fates for pyruvate 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 Be SURE you can interconvert Keq and standard state free energy change Be SURE you can use Eq. 3.12 to generate far right column of Table 19.1 Hexokinase 1st step in glycolysis; G large, negative 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 - but is not the most important site of regulation of glycolysis - Why? Rx 2: Phosphoglucoisomerase Glucose-6-P to Fructose-6-P 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 . | Chapter 19 Glycolysis to accompany Biochemistry, 2/e by Reginald Garrett and Charles Grisham All rights reserved. Requests for permission to make copies of any part of the work should be mailed to: Permissions Department, Harcourt Brace & Company, 6277 Sea Harbor Drive, Orlando, Florida 32887-6777 Outline 19.1 Overview of Glycolysis 19.2 Coupled Reactions in Glycolysis 19.3 First Phase of Glycolysis 19.4 Second Phase of Glycolysis 19.5 Metabolic Fates of NADH and Pyruvate 19.6 Anaerobic Pathways for Pyruvate 19.7 Energetic Elegance of Glycolysis 19.8 Other Substrates in Glycolysis Overview of Glycolysis The Embden-Meyerhof (Warburg) Pathway Essentially all cells carry out glycolysis Ten reactions - same in all cells - but rates differ Two phases: First phase converts glucose to two G-3-P Second phase produces two pyruvates Products are pyruvate, ATP and NADH Three possible fates for pyruvate First Phase of Glycolysis The first reaction - phosphorylation of glucose Hexokinase or .