Question

Glycolysis and fatty acid oxidation are both affected by the [NADH]/[NAD+] ratio in the cell. If the conditions inside a cell are such that [NADH] >>[NAD+] what will be the effect on both pathways? Be sure to explain the direct connection between [NADH] and specific reactions in these and related pathways.

Answer 1

Ans. #1. Effect of [NADH] >> [NAD⁺] on Glycolysis:

The cell has a limited pool of NAD⁺/NADH. No new cofactors are generally synthesized, but the oxidized and reduced forms are kept recycling into each other during biochemical pathways.

Reaction 6 of glycolysis is catalyzed by glyceraldehyde-3-hosphate dehydrogenase. The enzyme requires NAD⁺ as cofactor. In this reaction, NAD⁺ is reduced into NADH.

At [NADH] >> [NAD⁺], the cell has depleted availability of NAD⁺.

Unavailability of NAD⁺ thus inhibits reaction 6 of glycolysis. Since product of on reaction acts as reactant for the next reaction, all the steps of glycolysis starting from reaction 6. The buildup of products of reactions before step 6 also causes allosteric inhibition of all the glycolytic reaction.

Thus, glycolysis stops when [NADH] >> [NAD⁺].

#2. Beta oxidation (step 3) also requires NAD⁺.

When [NADH] >> [NAD⁺], reaction 3 of beta oxidation will not be catalyzed due to unavailability of NAD⁺.

Thus, beta oxidation also is inhibited under depleted [NAD⁺].