Question about gluconeogenesis

[deleted647690]

I got this question wrong, and I never took biochem II, so I spent a lot of time awhile ago trying to teach myself the pathways. This is one of the major topics that I am worried about for the exam, and I guess I just need to reread the chapter in TBR on metabolism/read about it as much as I can online.


My thought process in answering this question was that during the exam was
High NADH levels===NADH is a product of Citric acid cycle
Therefore, it makes sense that OAA would be increased, since that is a product in the TCA.

I know that my thought process here is wrong...maybe since the TCA cycle is circular, and OAA isn't actually a final product?


So the correct answer was that the rate of gluconeogenesis will decrease.
So if NADH is being produced--->that would inhibit both TCA and glycolysis, right? Since we are not in an energy deficit (since NADH provides electrons to the ETC to produce ATP through oxidative phosphorylation)

So then inhibit TCA and glycolysis---->Thus we have the reverse of glycolysis occuring, gluconeogenesis?

So since glycolysis isn't occurring, gluconeogenesis must be occurring?



EDIT: That was my reasoning, but I was completely wrong because gluconeogenesis is actually decreasing

So basically, I thought, since NADH was being produced, that would inhibit glycolysis from occurring. Since glycolysis and gluconeogenesis are reciprocally regulated, gluconeogenesis must be increased. This was incorrect.

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[tvbbnumber41]

You're thought process is not wrong, but I think you may have misinterpreted the question. So if NADH production is being upregulated, this suggests there is a lack of NADH (because you're trying to produce more NADH). If you're trying to increase NADH production, you wouldn't want to convert the molecules (that would normally feed into systems producing NADH) into it's original structure.

This is how I thought of it, but I do agree that the wording of the question isn't so great. I wouldn't expect questions like this to be asked by AAMC. They are rather more straightforward.

 

[deleted647690]

You're thought process is not wrong, but I think you may have misinterpreted the question. So if NADH production is being upregulated, this suggests there is a lack of NADH (because you're trying to produce more NADH). If you're trying to increase NADH production, you wouldn't want to convert the molecules (that would normally feed into systems producing NADH) into it's original structure.

This is how I thought of it, but I do agree that the wording of the question isn't so great. I wouldn't expect questions like this to be asked by AAMC. They are rather more straightforward.

From looking online, it does seem that high NADH would indicate would prevent the conversion of lactate to pyruvate, which then feeds into gluconeogenesis. Based on their explanation, this was what they were looking for I think. It also mentioned in the passage that, "the conversion of lactate to pyruvate is coupled with the reduction of NAD+ to NADH. Pyruvate enters gluconeogenesis after being converted to OAA by pyruvate carboxylase."

However, I did not note this in the passage. I just went off what I came up with and reasoned above, but I wonder if there is an error in my reasoning; that NADH would inhibit glycolysis, thus gluconeogenesis would have to be upregulated. I guess it's more complex than that.

And thanks for the response

 

[Nugester]

Use Le Chatelier's principle:

Lactate + NaD+ > Pyruvate + NaDH

Too much product forces it go back to lactate. Pyurvate is the first necessary substrate in gluconeogenesis.

 

[deleted647690]

Use Le Chatelier's principle:

Lactate + NaD+ > Pyruvate + NaDH

Too much product forces it go back to lactate. Pyurvate is the first necessary substrate in gluconeogenesis.

Yeah, I see why that is correct now. I was just wondering why my reasoning is wrong.

 

[Nugester]

Yeah, I see why that is correct now. I was just wondering why my reasoning is wrong.

Because OAA isn't involved only in the Krebs Cycle. It could get shunted off to the Urea cycle, for example in which the levels might decrease. That uncertainty automatically strikes out A). Also, like you mentioned, all the intermediates in the Krebs cycle are constantly being formed and broken down. Lastly, NaD+ is reduced to get NaDH in the Krebs Cycle. If you have too much NaDH, by that logic, the Krebs Cycle would be inhibited too and OAA levels would not increase.