FitOldDog’s Paleo And Acetone Epiphanies With Respect To The Tricarboxylic Acid (TCA) Cycle Carbon Count Mystery – You Can’t Make Sugar From Fat (largely)?

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Photo of Hans Adolf Krebs from Wikipedia

Hans Adolf Krebs

This blog is in large part about safe exercise for better health based on the study of body awareness, and such awareness can usefully include a little Biochemistry, which is both interesting and critically important for your health!


The great apes, which include humans and gorillas, cannot make Vitamin C, having to find it in their diet or they suffer from a horrible disease, Scurvy.

For about 40 years, as a result of studying energy production in the body (my PhD thesis involved Vitamin B1, thiamine, which is a key player) I’ve been asking Biochemists the question, “Why can we not make sugar from fat, whilst we readily make fat from sugar?” I know the reason given in textbooks of Biochemistry relates to the Krebs or TCA cycle, being essentially a carbon accounting problem, rendering all carbon entering the cycle unavailable for the production of glucose. This is not totally correct, as you can make a little sugar (glucose) from fatty acids with odd numbers of carbons and from the glycerol component of triglycerides. But it appeared to be more than 90% true based on what I read in ‘Wise Tomes.’ These biochemists would just scratch their heads, and I suspect they wondered, “Why the hell is this pathologist asking me this – what did I do to him?” One said, “Maybe we accidentally became stuck on a Kaufmannian fitness peak and couldn’t get down?” Sounded reasonable!

Well, I think my recent foray into the world of the Paleo Diet, with the encouragement of my eldest son, Nick, of Shirts That Go fame, and Mark Sisson’s great book, The Primal Blueprint, may have provided me with the answer, but first let’s consider why certain species, including the great apes of which we are a member, cannot make Vitamin C.

Here is what one expert, Ron Kennedy, had to say, and it makes sense to me:

Ron Kennedy MD expert on Vitamin C“Why did these four mammals — humans, gorillas, guinea pigs and fruit bats — lose the ability to make ascorbate? Probably, because they could. I suspect that these four animals had abundant sources of ascorbate in their diets, and loss of ability to produce their own ascorbate did not put them at excess risk of being weeded out by natural selection. Only the human being has changed his dietary preferences since then. Humans are the only species to both eat meat and be unable to produce ascorbate. There are no other carnivores which cannot make ascorbate.”

Acetone in Nalgene BottleSo, along came my epiphany number one, based on Paleo Thinking, with my reasoning going like this: “Mammals cannot make sugar from fat because they didn’t need to, as they largely employed free fatty acids and ketones for energy generation, deriving the limited amount of  sugar (glucose) needed for brain (20%) and red blood red cell (100%) functions by making it out of certain amino acids (gluconeogenesis from glycogenic amino acids) in the liver and kidneys, on demand.” Mystery solved, right? They didn’t need to do this because glucose was not a major body fuel. But now I’m on a low carbohydrate diet this got me to thinking and researching, and I came across a fascinating article, which argues that we actually can make sugar (glucose) from fat via ketones, more specifically acetone.

This article, by Chris Masterjohn, was published in The Daily Lipid, being entitled, “We Really Can Make Glucose From Fatty Acids After All! O Textbook, How Thy Biochemistry Hast Deceived Me!”

Harper's Biochemistry is a great book, it need not be intimidating, just take your time as you don't need to understand the whole thing. From:

Harper’s Biochemistry is a great book, it need not be intimidating, just take your time as you don’t need to understand the whole thing and there’s no hurry.

If you are on a low carbohydrate diet, which I am like any good disciple of The Primal Blueprint, you make a lot of ketone bodies, and it appears that one such ketone, acetone (yes the paint thinner), can be converted fairly readily into glucose – how readily and efficiently I’m still not sure. So, it would appear that the mantra of the Biochemistry books I read over the years, that “The carbon count in the TCA cycle negates mammalian ability to turn fats into sugar,” is not strictly correct.

Epiphany number two: the carbon count restriction may not be correct, after I believed it all of those years? Don’t you hate that? Nope – I love to learn new stuff!

I refer you to the interesting article by Chris Masterjohn in The Daily Lipid, referred to above, and especially to the fascinating comment stream. I’ll have to think about all this!

Uhmm! Running on paint thinner! Why not!

Reminds me of that old piece of wisdom from Mark Twain:

“It ain’t what you don’t know that gets you into trouble. It’s what you know for sure that just ain’t so.”

-k @FitOldDog


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Disclaimer: As a veterinarian, I do not provide medical advice for human animals. If you undertake or modify an exercise program, consult your medical advisors before doing so. Undertaking activities pursued by the author does not mean that he endorses your undertaking such activities, which is clearly your decision and responsibility. Be careful and sensible, please.