Journal of Lipid Research (Oct 2000)
Structural and biosynthetic studies of a principal bile alcohol, 27-nor-5β-cholestane-3α,7α,12α,24,25-pentol, in human urine
Abstract
The stereochemistry at C-24 and C-25 of 27-nor-5β-cholestane-3α,7α,12α,24,25-pentol, a principal bile alcohol in human urine, and its biosynthesis are studied. Four stereoisomers of the C26-24,25-pentols were synthesized by reduction with LiAlH4 of the corresponding epoxides prepared from (24S)- or (24R)-27-nor-5β-cholest-25-ene-3α, 7α,12α,24-tetrol. The stereochemistries at C-25 were deduced by comparison of the C26-24,25-pentols with the oxidation products of (24Z)-27-nor-5β-cholest-24-ene-3α,7α,12α-triol with osmium tetraoxide. On the basis of this assignment, the principal bile alcohol excreted into human and rat urine was determined to be (24S,25R)-27-nor-5β-cholestane-3α,7α,12α,24,25-pentol, accompanied by a lesser amount of (24R,25R)-isomer. To elucidate the biosynthesis of the C26-24,25-pentol, a putative intermediate, 3α,7α,12α-trihydroxy-27-nor-5β-cholestan-24-one, derived from 3α,7α, 12α-trihydroxy-24-oxo-5β-cholestanoic acid by decarboxylation during the side-chain oxidation of 3α,7α,12α-trihydroxy-5β-cholestanoic acid, was incubated with rat liver homogenates. The 24-oxo-bile alcohol could be efficiently reduced to yield mainly (24R)-27-nor-5β-cholestane-3α,7α,12α,24-tetrol. If a 25R-hydroxylation of the latter steroid occurs, it should lead to formation of (24S,25R)-C26-24,25-pentol. Now it has appeared that a major bile alcohol excreted into human urine is (24S,25R)-27-nor-5β-cholestane-3α,7α,12α, 24,25-pentol, which might be derived from 3α,7α,12α-trihydroxy-27-nor-5β-cholestan-24-one via (24R)-27-nor-5β-cholestane-3α, 7α,12α,24-tetrol.—Une, M., S. Takenaka, T. Kuramoto, K. Fujimura, T. Hoshita, and K. Kihira. Structural and biosynthetic studies of a principal bile alcohol, 27-nor-5β-cholestane-3α,7α,12α,24,25-pentol, in human urine. J. Lipid Res. 2000. 41: 1562–1567.
