Does excess NADH increase or decrease gluconeogenesis? - USMLE Forums
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Old 07-29-2015
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Default Does excess NADH increase or decrease gluconeogenesis?

Everybody says alcohol metabolism -> high NADH -> shunt oxaloacetate into malate -> depleted oxaloacetate, and that inhibits gluconeogenesis... But isn't malate required for gluconeogenesis via the malate shuttle anyways?

According to USMLE world, oxaloacetate in the mitochondria cannot get out, and needs to be converted to malate to get to the cytoplasm, where it is converted back into oxaloacetate and gluconeogenesis continues.

Doesn't this mean the NADH-driven conversion of oxaloacetate to malate should actually INCREASE gluconeogenesis?

(I am aware that there are other ways in which alcohol metabolism antagonizes gluconeogenesis, for example via the NADH-driven conversion of pyruvate to lactate, that does lead to less pyruvate and thus less gluconeogenesis, but that is not my focus in this question)
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Old 07-29-2015
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I don't get the question. If oxaloacetate is depleted, how can gluconeogenesis occur? Conversion of oxaloacetate to PEP occurs in both the cytosol and mitochondria.

I guess you are asking if increased malate increases gluconeogenesis? Only if NAD+ isn't depleted, which happens in increased ethanol metabolism.

Last edited by acff; 07-29-2015 at 09:14 AM.
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Quote:
Originally Posted by acff View Post
I guess you are asking if increased malate increases gluconeogenesis? Only if NAD+ isn't depleted, which happens in increased ethanol metabolism.
I think this point made it clear to me. For some reason I hadn't thought about how even though the malate shuttle is a part of gluconeogenesis, malate will have to turn back into oxaloacetate in the cytoplasm for gluconeogenesis to continue (which needs NAD+, and is unfavourable in the cytoplasm as well, as you pointed out).

Quote:
Conversion of oxaloacetate to PEP occurs in both the cytosol and mitochondria.
This part confused me, though. I thought oxaloacetate needed to be brought out of the mitochondria to be converted to PEP? I thought the point of the malate shuttle in gluconeogenesis is to get oxaloacetate out of the mitochondria?

Last edited by vocaloidict; 07-30-2015 at 12:05 AM. Reason: corrected a mistake
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