I was told in a physiology lecture that alcohol inhibits gluconeogenesis because 'NADH produced from ethanol catabolism leads to product inhibition'.

But is NADH not a reactant coenzyme of gluconeogenesis? It would make more sense if NADH inhibits glycolysis by product inhibition.

So, what is wrong here? Or is it because of some other reason why alcohol inhibits gluconeogenesis and leads to hypoglycemia?


Yes, this is the effect of metabolizing ethanol and also the reason why excess ethanol can lead to hypoglycemia.

Ethanol is oxidized by the alcohol dehydrogenase to acetaldehyde. This reaction consumes one molecule of NAD+ per molecule ethanol oxidized:

Ethanol + NAD+ <=> Acetaldehyde + NADH + H+

Acetaldehyde is oxidized by the acetaldehyde dehydrogenase in a second reaction in the mitochondria to Acetyl-CoA, which produces another molecule of NADH:

Acetaldehyde + NAD+  + CoA <=> Acetyl-CoA + NADH + H+

If you now take a look at gluconeogenesis, there is one critical step which needs NAD+: the oxidation of lactate to pyruvate by the lactate dehydogenase which then cannot be processed into oxalacetate, phosphoenolpyruvate and so on.

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Adding excess NADH shifts the reaction equilibrium completely to the side of lactate and also leads to the production of additional lactate, leading to hypoglycemia and lactic acidosis. Excess NADH from the ethanol oxidation inhibits the oxidation of fatty acids in the liver - this process also generates NADH for the production of ATP. NADH signals this process that enough energy is available in the cell. And finally excess NADH also inhibits the malate dehydrogenase reducing the amount of oxalacetate for gluconeogenesis further.

  • $\begingroup$ Good explanation $\endgroup$ – rhill45 Oct 12 '14 at 2:41

Partially correct. Please allow me to explain. It is mentioned above: "shifting the equilibrium to the production of additional lactate, leading to hyperglycemia..."

It's true that excess NADH production as a result of alcohol consumption inhibits oxidation of lactate to pyruvate via lactate dehydrogenase. But, this leads to HYPOglycemia, not HYPERglycemia, because lactate is not adequately converted to pyruvate to meet the body's metabolic demands.

What are the repercussions? Less pyruvate created ---> less of its conversion to oxaloacetate, which under normal conditions, would usually traverse across the mitochondrial membrane into the cytoplasm to be converted to PEP via PEPCK. Less oxaloacetate as a result of less pyruvate being shunted towards the gluconeogenesis pathway ultimately leads to HYPOglycemia.

Although ethanol on its own (like if you were to drink grain alcohol) would result in a drop in blood sugar, and this is ESPECIALLY a danger for individuals with Type 1 diabetes. Beer, wine, and common spirits rarely cause a drop in blood sugar because they also provide carbohydrates. These carbohydrates help to maintain blood sugar, if not elevate it on a binge.

  • 1
    $\begingroup$ Welcome to SE Biology. I think hyperglycemia was probably just a typo in @Chris post. It would probably be better to just edit the accepted answer to correct the mistake. $\endgroup$ – Roland May 28 '17 at 7:26
  • $\begingroup$ You can simply correct typos in answers. As I have no corrected mine (thanks for spotting it), your answer is obsolete. $\endgroup$ – Chris May 28 '17 at 8:17

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