Imagine a scenario in which some person is unable to absorb any dietary cholesterol because of some intestinal mutation (for example). Thus, they have no cholesterol available from their diet for steroid hormone synthesis, bile acid synthesis, or any other process that requires cholesterol.

If that person had to synthesize all of their cholesterol requirements de novo (i.e. from acetyl-CoA), how much energy would that require on a daily basis? In biochemistry we talk about de novo cholesterol synthesis, but a lot of the time it is glanced over because it would be so energetically unfavorable to synthesize it when you can get it from your diet.

I'm curious to know... if we could somehow inhibit all cholesterol absorption and forced the body to make all its own cholesterol, then how much excess energy could we burn? Could we use that as a weight loss therapy?

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    $\begingroup$ You can easily figure this out by (1) counting up the stoichiometry of the cholesterol synthesis pathway and (2) multiplying by the amount of cholesterol lost each day by an average person. $\endgroup$
    – Roland
    Nov 25 '15 at 20:00
  • $\begingroup$ @Roland how much cholesterol is lost each day by an "average person"? Are you sure that's fairly constant across adults? $\endgroup$ Nov 25 '15 at 20:01
  • $\begingroup$ @Roland I think the problem is trying to estimate the daily losses of cholesterol from conversion to "other substances" within the body - i.e. bile acids, steroid hormones, etc. I'm not sure how or what those estimates would be and if they would differ significantly between adults. $\endgroup$ Nov 25 '15 at 20:20
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    $\begingroup$ It's gonna be a ballpark estimate of course, as always with whole-body metabolism. This paper ncbi.nlm.nih.gov/pmc/articles/PMC297311 puts the loss of cholesterol at about 1g / day. Since cholesterol is not catabolized in the body, it should be a pretty good estimate of total cholesterol turnover. I think modifications like bile acid conjugation etc are minor in comparison to loss of the entire sterol backbone. Of course, you will see some variation between individuals, diets, etc. $\endgroup$
    – Roland
    Nov 25 '15 at 22:38
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    $\begingroup$ Great, let us know what you come up with! Also, consider that the acetyl-CoA generated by sterol syntheis is a metabolic cost as well, as it could otherwise have been used to generate ATP. $\endgroup$
    – Roland
    Nov 26 '15 at 6:14

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