Lactic acidosis type A results from tissue hypoperfusion. In the anaerobic state, pyruvate accepts electrons from NADH via lactate dehydrogenase (LDH) to form lactate, regenerating NAD+. Why is NAD+ regeneration critical here?

• A NAD+ is required as a substrate by glucose-6-phosphate dehydrogenase in the pentose phosphate pathway
• B NAD+ is required by GAPDH (step 6 of glycolysis) to allow continued ATP generation from glucose in the absence of oxygen ✓
• C NAD+ regeneration activates pyruvate kinase by allosteric stimulation
• D NAD+ is needed by the electron transport chain to regenerate ATP from NADH directly

Explanation

Glycolysis requires NAD+ at the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) step (step 6): G3P + NAD+ → 1,3-BPG + NADH. Without NAD+ regeneration, GAPDH is inhibited and glycolysis halts, preventing any ATP production from glucose. Under anaerobic conditions, the mitochondrial ETC cannot oxidise NADH (no O2 as terminal acceptor), so LDH converts pyruvate to lactate while regenerating NAD+, enabling glycolysis to continue and produce 2 ATP/glucose. This anaerobic ATP is critical for cell survival during hypoxia. G6PD uses NADP+, not NAD+. Pyruvate kinase is not allosterically regulated by NAD+. ETC regenerates ATP using NADH, not the reverse.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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