Cholesterol metabolites

B. S. Reddy and K. Watanabe, Effect of cholesterol metabolites and promoting effect of lithocholic acid in colon carcinogenesis in germ-free and conventional F344 rats. Cancer Res., 1979, 39, 1521. 

Cholesterol also serves as a precursor to other important molecules. Bile acids aid in lipid absorption during digestion. Steroid hormones all derive from cholesterol, including the adrenal hormones that maintain fluid balance Vitamin D, which is an important regulator of calcium status and the male and female sex hormones. Although humans wouldn t survive in one sense or another without cholesterol metabolites, cholesterol brings with it some well-known side effects. Doctors find cholesterol derivatives, being essentially insoluble in water, in the deposits (plaque) that characterize diseased arteries. 

Sonoda, J., Chong, L.W., Downes, M., Barish, G.D., Coulter, S., Liddle, C., Lee, C.H. and Evans, R.M. (2005) Pregnane X receptor prevents hepatorenal toxicity from cholesterol metabolites. Proceedings of the National Academy of Sciences of the United States of America, 102, 2198-2203. 

Nakamura, H. (1966) Effect of y-oryzanol on hepatic cholesterol biosynthesis and fecal excretion of cholesterol metabolites. Radioisotopes, 25, 371-374. 

Our rationale for such usage is based upon the tenet that the rates of various biochemical processes associated with cholesterol metabolism cannot be the same in all individuals. Therefore, in diseased persons the biochemical reactions would generate cholesterol metabolites in amounts that are very different from the ones produced by healthy individuals. Although several of these steroidal species may be metabolized and excreted, many of them would remain and enter blood circulation. Hence, the amounts of these steroids observed in sera of diseased subjects would be very different from the ones found in healthy individuals. 

Paul SM, Doherty JJ, Robichaud AJ, et al. The major brain cholesterol metabolite 24(S)-hydroxycholesterol is a potent allosteric modulator of N-methyl-D-aspartate receptors. J Neurosci. 2013 33 17290-17300. 

Patti, G.J., Shriver, L.P., Wassif, C.A., Woo, H.K., Uritboonthai, W., Apon, J., Manchester, M., Porter, F.D. and Siuzdak, G. (2010) Nanostructure-initiator mass spectrometry (NIMS) imaging of brain cholesterol metabolites in Smith-Lemli-Opitz syndrome. Neuroscience 170, 858-864. 

This fundamental role of bile salts in the intestinal absorption of sterols is a reflection of the potential requirements for this cholesterol metabolites in various steps of intraluminal and epithelial cell mechanisms of cholesterol absorption (Figure 1), These include solubilization of cholesterol in the intestinal lumen by mixed micelles, containing biliary bile salts and phospholipids, and the products of triglyceride digestion modification of the intestinal surface barriers to cholesterol transfer, including the un-stirred water layer" and the mucin "coat" and the cellular esterification of cholesterol prior to incorporation of the resulting esters into the lipoprotein core lipids. 

Zasloff, M., Williams, J.I., Chen, Q., Maeder, T., Holroyd, K., Jones, S., Kinney, W., Cheshire, K, and McLane, M. (2001) A spermine-coupled cholesterol metabolite from the shark with potent appetite suppressant and antidiabetic properties. Int. J. Obes., 25, 689-697. 

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