Effect of NADH on Fructose 1-6-bisphosphatase and Glucose-6-phosphatase

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Hypertrophy22

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I had a practice question that read: "High levels of NADH will inhibit which of the following enzymes?"

The answer choices Fructose 1-6-bisphosphatase and Glucose-6-phosphatase were both explained to be incorrect because:
"This enzyme is required for gluconeogenesis. High levels of NADH would indicate the cell is energetically satisfied, and gluconeogenesis would be expected to decrease."

To me that would imply that both enzymes have decreased activity with high levels of NADH and therefore be inhibited.
Am I missing something here? Is there a reason this isn't considered inhibition?
 

EmilKraepelin55

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It’s not the best explanation as to why NADH affects this process in the context of this question. NADH is produced from NAD+ when Fructose 1,6 bisphosphate is converted to DHAP and Glycerol-3-P. From here NADH is used to convert pyruvate into lactate in the presence of lactate dehydrogenase. And so it follows that if NADH is high that more pyruvate would be converted to lactate, essentially spurring on more glycolysis to yield more useable energy (ATP). However, in the context of this question, it’s actually the ATP that would directly inhibit glucneogenesis by working on fructose 1,6 bisphosphatase and Glucose-6-phosphatase.

The thing to remember here is that glycolysis to lactate is an anerobic process, creating minimal ATP. So elevations in NADH should not produce the amount of ATP required to inhibit Gluconeogenesis by inhibiting these enzymes, which is a process that occurs in energy depleted scenarios and not necessarily as a result of anoxic conditions where oxidative phosphorylation isn’t possible.

*Had to make a correction in bold

Increased NADH can inhibit Gluconeogenesis by draining the available pyruvate and oxaloacetate required to fuel the process, instead producing more lactic acid. See ethanol metabolism and the acidosis that can ensue as a result of NADH accumulation.
 
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Hypertrophy22

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Thanks for the explanation. I had to stare at the gluconeogenesis and glycolysis pathways and compare for some time after your initial post but it makes sense with the correction.
I appreciate it!
 
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