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NBME 21 Answers

nbme21/Block 2/Question#29 (reveal difficulty score)
A healthy 25-year-old man is participating in ...
Alanine 🔍 / 📺 / 🌳 / 📖
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 +27  upvote downvote
submitted by assoplasty(108)
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Fats are ketogenic (except odd chain FA), so they produce ketones for energy production (Acetyl-CoA) rather than glucose. If the question asked what the primary source of energy production was, it would still be glycogen (and not ketones), because this is within 24 hours. However after 24 hours the answer could be ketone bodies. Regardless, the question specifically said the pt had a serum glucose of 100, indicating that we are looking for something that provides a substrate for gluconeogenesis.

During periods of starvation, substrates for gluconeogenesis come from two sources: (1) breakdown of existing muscle, or (2) via odd-chain FA through propionyl-CoA. (*Valine also feeds into propionyl CoA, but is not involved during starvation --> see below)

(1) The alanine-pyruvate cycle provides this (glutamine in muscle + pyruvate --> alanine --> goes to liver --> transamination to alpha-ketoglutorate --> pyruvate is separated from glutamine --> glutamine goes to urea cycle, pyruvate goes on to gluconeogenesis). Lactate can also be used (this could have been a right answer if it were listed).

(2) Odd chain FAs are also glucogenic, but stearic acid (provided in the answer choice) isn’t odd chain, so it is only ketogenic and can be ruled out.

Although valine (and other branched a.a.) feed into Propionyl-CoA, they are not used in starvation because starvation strictly relies on hepatic gluconeogenesis. These a.a. are not metabolized in the liver because the liver lacks branched-chain a.a. transferase enzyme. In First Aid, Biochem section, under Fasting/Starvation, in both the “fasting state” (which is within the time frame of this question), or the “starvation state,” both utilize hepatic gluconeogenesis. My assumption is that valine is used during regular metabolism, and not during periods of starvation.

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hello  I want to re-emphasize something that @assoplasty has already stated :). The Q-stem states serum glucose = 100, and the Q asks why the patient is able to maintain normoglycemia. Therefore, you can immediately eliminate choices A and C because acetoacetate and beta-hydroxybutyrate are sources of energy during ketogenesis -- ketogenesis does not provide glucose energy sources. +14
chandlerbas  ^ this checks out: valine and isoleucine are broken down in the muscle into branched chain 2 oxo acid via branched chain aminotransferase (reversible) then the valine and isoleucine leave the muscle and swims to the liver to be acted on by branched chain 2 oxo acid DH (irreversible). So bascially the process from taking BCAA valine and isoleucine requires 2 enzymes. the first enzyme is in the muscle, and the second enzyme is in the liver (for simplification purposes --> both organs contain both enzymes but dont have the same affinity for their substrate). source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1147506/?page=4 so you're right to say that the liver +5
toxoplasmabartonella  Thank you for such a great explanation. Isn't it glutamate instead of glutamine that combines with pyruvate in muscle to yield alanine for Cahill cycle? +1
almondbreeze  @ toxoplasmabartonella think you are right +
revanthshanmukh  its given that methionine histidine and valine are glucogenic AA.nso why not these form the glucose in the body first compared to alanine? +
johnnybravo  @revanthshanmukh Although those are indeed glucogenic AA, they are also essential AA, which means they must be acquired from the diet. This patient in the stem has been fasting. FA 2020 pg 91, Lactate and Alanine help contribute to gluconeogenesis during starvation (1-3 days) +1



 +21  upvote downvote
submitted by hayayah(1212)
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P. 91 of FA has a quick explanation for this!

Basically once you're in a starving state there's still hepatic gluconeogenesis going on (as well as using FFA) but the gluconeogenesis is coming from peripheral tissue lactate and alanine.

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 +2  upvote downvote
submitted by frimmy_11(2)
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Muscle protein breaks down into the amino acid alanine which enters Cahill Cycle to form glucose ...

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volcanobuns  @frimmy_11 Why would protein break down after only 20 hours? Shouldn’t fat be the major contributor now? Also, if protein is being used, then why isn’t valine the choice? Valine is also glucogenic. +



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submitted by hello(429)
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I want to re-emphasize something that @assoplasty has already stated :).

The Q-stem states serum glucose = 100, and the Q asks why the patient is able to maintain normoglycemia.

Therefore, you can immediately eliminate choices A and C because acetoacetate and beta-hydroxybutyrate are sources of energy during ketogenesis -- ketogenesis does not provide glucose energy sources.

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 +0  upvote downvote
submitted by volcanobuns(1)
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@frimmy_11 Why would protein break down after only 20 hours? Shouldn’t fat be the major contributor now? Also if protein is being used, then why isn’t valine the choice? It’s also glucogenic.

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sd22  It's not asking for the major contributor, just which one of the choices contributes anything at all. +



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submitted by hello(429)
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Please help

Why is valine incorrect?

An explanation below says that valine would be converted to glucose during regular metabolism?

Regular metabolism = fed state, so why would valine even be converted to glucose?

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ali_hassan  FA 2018 pg.91 - Starvation days 1 - 3: hepatic gluconeogenesis from peripheral tissue lactate and alanine. that's all +



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submitted by unknown001(9)
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that stuid mneuminic of MET HIS VALENTINE made me switch from alanine to valine.

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