Cholesterol metabolism pathways - are the intermediates more important than the products?

Abstract

Every cell in vertebrates possesses the machinery to synthesise cholesterol and to metabolise it. The major route of cholesterol metabolism is conversion to bile acids. Bile acids themselves are interesting molecules being ligands to nuclear and G protein-coupled receptors, but perhaps the intermediates in the bile acid biosynthesis pathways are even more interesting and equally important. Here, we discuss the biological activity of the different intermediates generated in the various bile acid biosynthesis pathways. We put forward the hypothesis that the acidic pathway of bile acid biosynthesis has primary evolved to generate signalling molecules and its utilisation by hepatocytes provides an added bonus of producing bile acids to aid absorption of lipids in the intestine.

Keywords: COVID-19; G protein-coupled receptors; cholestenoic acids; glutamate receptors; inborn errors of metabolism; mass spectrometry; nuclear receptors; oxysterols; sterols.