Precursors of Coprosterol and the Bile Acids in the Animal Organism

Abstract

THE transformation of cholesterol into coprosterol in its passage through the body involves a reduction of the C₅:C₆ double bond, and a transition from the allocholanic—to the cholanic-ring system. Although it is established that the bacterial flora of the intestine is concerned in the reduction process, the mechanism by which the stereochemical change is brought about is unknown. A clue was afforded by a study of the properties of cholestene—3:4—diol, a primary oxidation product which is formed under various conditions of mild oxidation from cholesterol, and is also a constituent of the resinous product called oxycholesterol¹. Being an glycol, this substance easily rearranges by loss of water into the corresponding ketone, that is, cholestenone. Since cholestenone (= coprostenone) yields coprostanone on reduction, which in turn is reducible to coprosterol (= coprostanol) and epi-coprosterol^2,3, we formed the working hypothesis that the reactive primary oxidation product, cholestene-diol, may play a role in cholesterol metabolism, giving rise to the formation of cholestenone as an intermediary product. On this assumption, cholestenone and coprostanone, and not cholesterol itself, are the immediate precursors of coprosterol which is formed from them in the intestine by bacterial reduction. Further, an explanation is afforded for the origin of the epi-hydroxycholane system in lithocholic acid (and the other bile acids?)⁴, which may be derived from epi-coprosterol by oxidative cleavage of the side chain with loss of acetone.