I am reading old papers by HA Krebs in which he suggests ways to estimate the ratio of NAD+/NADH inside the mitochondria using acetoacetate and B-hydroxybutyrate. I found a more modern researcher who suggests a particular formula and set of constants to use to make this calculation. Getting B-hydroxybutyrate is easy: any commercial lab offers that. But acetoacetate / B-ketobutyrate appears to be a specialty test that only niche labs handle. Does anyone have insights on why acetoacetate might be harder to obtain? Maybe it is just not used as a clinical marker and tends to be useful only in research?
Source for Acetoacetate / B-Ketobutyrate Measurements?
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Your question would probably be better served in the mcat or step 1 forums, but I'll give it a shot. I've never seen serum acetoacetate levels measured in a clinical setting, so definitely not an expert. It seems it would only be clinically useful in differentiating between ketosis caused by alcohol vs that caused by starvation and DKA. Pretty sure you should be able to make that differentiation, and quicker, with a decent h&p and other more routine labs. So not really necessary after initially establishing dx of ketosis. Also, beta-hydroxybutyrate is converted to acetoacetate, so a quantitative acetoacetate would falsely show worsening ketosis even as the clinical picture improves.
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So it sounds like acetoacetate has very limited clinical application, and that's probably the reason for difficulty finding the test.
Given limited clinical application, it probably isn't any better to post this question in step 1 forum. In osteopathic tradition, you look for causes of things, and approximating the NAD+/NADH ratio seems to be a reasonable way to help identify fatigue syndromes that defy normal clinical diagnosis. A lot of things in Krebs cycle and Electron Transport Chain can break, and having some way to objectively classify different types of fatigue symptoms might be useful.
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If anything in the electron transport chain breaks, you're going to have a lot more to worry about than trying to determine cause of ketosis, see cyanide poisoning
Good point. I should not have used the word 'break'. If electron transport chain completely breaks you have bigger problems, like surviving the next 10 minutes.
What I should have said is that electron transport chain can become inefficient. Since NAD-to-NADH ratio being too low can downregulate the Krebs cycle, and any inefficiency in electron transport chain can affect the ability to convert NADH back to NAD. NAD to NADH ratios can be a useful way to identify some energy metabolism defects.
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