Fundamentals of Biochemistry Third Edition Donald Voet • Judith G. Voet • Charlotte W. Pratt Chapter 15 Glucose Catabolism Copyright © 2008 by John Wiley & Sons, Inc.

Overview of Glycolysis

Step 1 Not really that reversible

Hexokinase

Step 2

Step 3

Step 4

Step 5

Step 6

Determination of the Mechanism

Step 7

Step 8

Figure 15-12

Step 9

Step 10

What did we accomplish? Overall, we took 1 glucose molecule and made: 2 pyruvates, 2 NADH, 2 ATP, and 2 H2O Net equation

Fates of Pyruvate

Lactate Dehydrogenase (LDH)

Alcoholic Fermentation by Yeast

Energy Efficiency ΔG°’ = -196 kJ/mol ΔG°’ = -235 kJ/mol To make 2 ATP = ΔG°’ = 61 kJ/mol Therefore, lactate production is 61/196 = 31% efficient Therefore, ethanol production is 61/235 = 26% efficient Under biochemical concentrations, the reactions are actually >50% efficient

Regulation of Glycolysis

PFK is main regulatory enzyme Activators: ADP; AMP; F2,6P Other substrate: F6P Substrate/inhibitor = ATP

Other Mechanisms Is flux controlled only by ATP? Seems like yes, but no Glycolytic flux varies by 100 fold ATP concentration varies only 10 fold ATP concentration is buffered by other enzymes such as creatine kinase and adenylate kinase However, [ATP] is 50X > [AMP] and 10x > [ADP] Therefore, a 10% change in [ATP] and result in 100% change of ADP and 400% change of AMP

Substrate cycling A ↔ B If top equation were correct, then thermodynamics would be violated. One enzyme cannot be favorable in two directions Substrate cycling uses two different enzymes.

Substrate cycling PFK FBPase

Other Hexoses

Pentose Phosphate Pathway Stage 1 Stage 2 Stage 3

Figure 15-34

Figure 15-35