Carbohydrate metabolism question

[HopefulMDclass2020]

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First off, this is a question from TPR FL exam 3. If I am not allowed to post this, I apologize in advance, and I will quickly take it down.

Alcohol dehydrogenase metabolizes ingested alcohol via oxidation, producing NADH during the course of the reaction. Which of the following is most likely to occur?

A. Intracellular levels of OAA will increase.
B. Lactate concentrations in the blood will decrease.
C. The rate of gluconeogenesis will decrease.
D. Levels of pyruvate as a gluconeogentic substrate will increase.

C. NADH levels will increase as a result of the oxidation of ethanol. Because pyruvate carboxylase is inhibited by increased intracellular NADH levels, the rate of conversion of pyruvate to OAA will decrease (choice A is false and may be eliminated). Increased NADH levels will shift the equilibrium of the reversible reaction between pyruvate and lactate toward lactate, reducing pyruvate levels as well (choice B is false and may be eliminated). As a result of decreased availability of both OAA and pyruvate (choice D is false and may be eliminated), two important gluconeogenic substrates, the rate of glucose production via gluconeogenesis will decrease (choice C is true and the correct answer). Because of this, one important effect of chronic alcoholism is hypoglycemia due to impaired glucose synthesis.

I answered A. I was under the impression that gluconeogenesis was activated during times of high hepatic cellular energy, such as increase ATP, NADH, and glucagon. This implies that the cell is energetically satisfied enough to produce glucose for the rest of the body and stimulate pyruvate carboxylase to produce OAA. And during times of low ATP, low NADH, and insulin, it will stimulate pyruvate dehydrogenase in order to replenish the energy. What is wrong with this logic?

 

[evaporation132]

is this a question on the MCAT? (don't know what TPR is) If so was there any more background info given or are we suppose to have memorized the NADH function chemical pathways and how they relate to every other thing such as lactate and gluconeogenesis ? kinda scared me

 

[EParker37]

I answered A. I was under the impression that gluconeogenesis was activated during times of high hepatic cellular energy, such as increase ATP, NADH, and glucagon. This implies that the cell is energetically satisfied enough to produce glucose for the rest of the body and stimulate pyruvate carboxylase to produce OAA. And during times of low ATP, low NADH, and insulin, it will stimulate pyruvate dehydrogenase in order to replenish the energy. What is wrong with this logic?

The question isn't really asking about the control schema for the pathway, but rather recognizing that important components of the pathway are missing altogether. But if we have excess NADH, the cell is satisfied, and therefore more glucose is not necessary. Gluconeogenesis is really all about providing for glucose in times of fasting, not really as a storage pathway.

 

[HopefulMDclass2020]

The question isn't really asking about the control schema for the pathway, but rather recognizing that important components of the pathway are missing altogether. But if we have excess NADH, the cell is satisfied, and therefore more glucose is not necessary. Gluconeogenesis is really all about providing for glucose in times of fasting, not really as a storage pathway.

I am still not fully grasping this. I found this on wikipedia for the inhibition of pyrvuate dehydrogenase.

"Pyruvate dehydrogenase is inhibited when one or more of the three following ratios are increased: ATP/ADP, NADH/NAD+ and acetyl-CoA/CoA."

And since we know the two paths of pyruvate is either pyruvate dehydrogenase forming Acetyl-Coa, or pyruvate carboxylase to form OOA. I would assume when the former is inhibited the latter will be stimulated. This question is essenitally ruining the whole conceptional framework I had over the pathways of glycolysis and gluconeogenisis.

Thank you in advance.

 

[EParker37]

I am still not fully grasping this. I found this on wikipedia for the inhibition of pyrvuate dehydrogenase.

"Pyruvate dehydrogenase is inhibited when one or more of the three following ratios are increased: ATP/ADP, NADH/NAD+ and acetyl-CoA/CoA."

And since we know the two paths of pyruvate is either pyruvate dehydrogenase forming Acetyl-Coa, or pyruvate carboxylase to form OOA. I would assume when the former is inhibited the latter will be stimulated. This question is essenitally ruining the whole conceptional framework I had over the pathways of glycolysis and gluconeogenisis.

Thank you in advance.

It can also be transaminated into alanine, and reduced to lactate. This question is saying that because we have an overabundance of NADH, the NADH will be oxidized, and the Pyruvate will get reduced, creating more lactate and not leaving any pyruvate available for gluconeogenesis. The pyruvate to lactate reaction is favored when there is excessive intracellular NADH available,

 

[HopefulMDclass2020]

It can also be transaminated into alanine, and reduced to lactate. This question is saying that because we have an overabundance of NADH, the NADH will be oxidized, and the Pyruvate will get reduced, creating more lactate and not leaving any pyruvate available for gluconeogenesis. The pyruvate to lactate reaction is favored when there is excessive intracellular NADH available,

Okay, that makes perfect since now. I forgot about the third pathway producing lactate. One more question, so obviously pyruvate dehydrogenase is inhibited with high NADH levels, I just always assumed that the opposite would be true for pyruvate carboxylase. I guess we would say that both are inhibited at high NADH levels, which will then activate lactate dehydrogenase?

 

[EParker37]

Okay, that makes perfect since now. I forgot about the third pathway producing lactate. One more question, so obviously pyruvate dehydrogenase is inhibited with high NADH levels, I just always assumed that the opposite would be true for pyruvate carboxylase. I guess we would say that both are inhibited at high NADH levels, which will then activate lactate dehydrogenase?

I wouldn't assume that it is inhibiting the pyruvate carboxylase directly, just that there isn't any pyruvate available to be catalyzed into OAA. As far as I can remember, the only direct inhibitor of PC is the presence of high levels of intracellular ADP, indicating a need for pyruvate to enter the Krebs Cycle and make more ATP.