Kaplan Full-Length 3; Bio/Biochem Question #3

[MrRed]

Which of the following best explains why, after several weeks of starvation, acetyl-CoA is used almost exclusively to produce ketone bodies?

A. Gluconeogenesis depletes the supply of oxaloacetate which is essential for the entry of acetyl-CoA into the Krebs cycle.
B. Starvation leads to the selective production of the enzyme that catalyzes the formation of ketone bodies.
C. Acetyl-CoA cannot be converted into pyruvate; therefore, it cannot enter the gluconeogenic pathway.
D. Triacylglycerols are mobilized from adipose tissue.


The correct answer is listed as A; I thought the best answer was C; however I suppose A would be a better answer, but I still don't like that answer itself.

Ketone bodies are produced by the reaction:

1. 2 Acetyl-CoA + H2O --> acetoacetate + 2CoA + H+

2. acetoacetate + NADH + H+ ---[D-hydroxybutyrate dehydrogenase]--> NAD+ + D-3-Hydroxybutyrate
(mind you step 1 is actually 3 steps, this is only the net)

They are degraded in the process:
1. D-3hydroxybutyrate + NAD+ ---[dehydrogenase]--> acetoacetate
2. acetoacetate + succinyl-CoA --[CoA transferase]--> Succinate + acetoacetyl-CoA
3. acetoacetyl-CoA + CoA --[thiolase]--> 2 acetyl-CoA

Then the 2 acetyl-CoA enter the citric acid cycle anyway. So I don't see why A is correct.
Maybe I'm just not as familiar with the fasting process and what bio-pathways are most upregulated compared to others, but I don't get it.

I think, maybe I should just be considering ONLY the liver? If this is the case; which I can see gluconeogenesis and ketone body synthesis happening and gluconeogenesis using alot of OAA to make PEP; then I still don't get it.

If the liver cells need ATP for themselves they are going to put acetyl-CoA into the citric acid cycle as first priority. Only once they themselves have enough ATP to function will they even be able to make ketone bodies.
So is the question just a poor question in general? Or am I missing something blatant?

Confused lol

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[MrRed]

Alright so I'm just going to talk to myself here quick and maybe someone can confirm or deny what I'm saying:

So during starvation (After a few weeks; and they are talking about birds here with a lot of fat on them) the liver will be participating in both gluconeogenesis, fatty acid oxidation, and ketone body synthesis. Glucagon and epinephrine upregulate all of these pathways, I'm assuming.

So gluconeogenesis needs pyruvate to be carboxylated to form OAA (pyruvate carboxylase: ATP + pyruvate + HCO3- --> OAA + + ADP + Pi) to actually carry out the biosynthetic pathway.
How else can OAA be made in the cell?
From what I know OAA is primarily formed through oxidation of malate (L-malate + NAD+ +2H+ --[malate dehydrogenase] --> OAA + NADH + H+)
or from the combination of carbonic acid with pyruvate.

So the liver is busting out a ton of beta-oxidation and acetyl-CoA is flying all over the place. There's so much acetyl-CoA so the liver can't use all of it by itself so it just pumps it into the blood in the form of ketone bodies.
However, even if the liver had the OAA potential to use all of the acetyl-CoA by itself, isn't that beside the point?
It takes a full 6 high energy phosphates and 2NADH to make 1 glucose from 2 pyruvate (4ATP, 2 GTP, 2NADH); so obviously the hepatocyte in question has to be performing aerobic respiration.
So I guess that I see why OAA would be depleted, but if you're performing gluconeogenesis you're breaking down muscle for protein; and I know you can form malate from aspartate. So you're obviously forming more OAA?
Then when the cell has enough ATP (hepatocyte in question) it will of course make ketone bodies + glucose for other cells to use; but then as soon as it needs more ATP then it will postpone ketone body synthesis + gluconeogenesis (or however the actual complex regulation works) until it has enough ATP to continue on.

I don't know... the whole thing just seems like a rather annoying question that if you actually think deep into it, I actually do believe C would be a better answer.

Anyone for some discussion?

--actually time to meditate then bed any prospective individuals who would like to debate I will see you tomorrow