When a person's glucose and glycogen stores are depleted, which can occur due to fasting or due to a diet consisting largely of fat (like eskimo diets), the body produces its energy by breaking down triglycerides into fatty acids. Fatty acids can be then converted to Acetyl-CoA, which can consequently enter the citric acid cycle, generating ATP.*

Now normally when a cell does not receive sufficient oxygen to undergo its natural processes, it usually breaks down glucose anaerobically to generate ATP and lactic acid. However, in the case where the body is running off fatty acids (e.g. fast, or fat/protein only diet), how does the body respond to such anaerobic situations?

*(Note: In this situation many fatty acids are first taken up into the liver and converted to ketone bodies, which are subsequently converted to Acetyl-CoA after being taken up in the required tissues, hence causing "ketosis" as in the title)


2 Answers 2


You are correct in thinking that fatty acids cannot be metabolised anaerobically. However, in the type of metabolic state that you are describing, blood glucose will be maintained by the liver to support tissues or cells which are more or less dependent upon anaerobic metabolism. The classic example of such a cell type is the red blood cell which as no mitochondria and so cannot use the TCA cycle. The brain is also heavily dependent upon glucose.

The liver exports glucose that it has produced via gluconeogenesis from amino acid skeletons, as well as from glycerol produced as a result of fat metabolism.


In reality, a cell will die almost immediately in such anaerobic conditions. The question itself can be taken another way. That is, how does the body fuel anaerobic metabolism in the relative absence of glucose. It is important to understand that stored ATP and CP (creatine phosphate) provide energy anaerobically, but can be refueled by beta oxidation of fatty acids that occurs between bouts where energy needs exceed oxygen supply. So someone on a high fat diet with virtually zero carbs is going to perform their anaerobic work mostly from ATP-CP without having to turn to gluconeogenesis. Glucose obligate tissues, primarily the brain, nerves, liver and pancreas will require glucose (or ketones) in the absence of endogenous glucose, and so they will need to receive these via gluconeogenesis of canabalized tissues or consummed protein, however the brain does not last for more than about 30 seconds on fast glycolysis anyway so to say that the body makes glucose from protein to allow anaerobic metabolism to go on is not accurate. The body turns to gluconeogenesis primarily to provide substrates for glucose dependent tissues to use in oxidative phosphoylation, not in anaerobic pathways.

At any rate, the ANSWER to the question as posed "Is anaerobic activity during ketosis possible," YES because you have stores of CP and ATP that don't require oxygen to access, but gluconeogenesis during ketosis is not activated by a need for anaerobic energy sources (fast glycolysis) but by glucose dependent tissues need for glucose for oxidative phosphorylation.

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    $\begingroup$ Two points to you as a new contributor. 1. It's best to provide sources in support of assertions, e.g. "the brain does not last for more than about 30 seconds on fast glycolysis" (what do you mean by fast glycolysis, anyway?). 2. Wbat do you mean by "the oxidative phosphorylation needs of the brain"? Oxidative phosphorylation is a means to an end (production of ATP), not a need in itself. $\endgroup$
    – David
    Nov 5, 2018 at 22:10
  • $\begingroup$ It may take a few posts on this S.E. to get a feel fort what is considered to be a baseline level of knowledge in biochem. $\endgroup$ Nov 5, 2018 at 23:35
  • $\begingroup$ Will work on an edit. "Oxidative Phosphorylation needs" should be "aerobic energy needs" "Fast Glycolysis" is glycolysis that results immediately in lactate/pyruvate rather than "slow glycolysis" which is going to send substrates directly into the TCA cycle. $\endgroup$ Nov 5, 2018 at 23:44
  • $\begingroup$ biomechanix.net/a-quick-breakdown-of-fast-and-slow-glycolysis $\endgroup$ Nov 5, 2018 at 23:48
  • $\begingroup$ Something wrong with your link. It points to a page that gives me a "401 Forbidden". $\endgroup$
    – David
    Nov 7, 2018 at 9:08

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