Structural and biosynthetic studies of a principal bile alcohol, 27-nor-5{beta}-cholestane-3{alpha},7{alpha},12{alpha},24,25-pentol, in human urine

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Structural and biosynthetic studies of a principal bile alcohol, 27-nor-5ß-cholestane-3 ${alpha}$ ,7 ${alpha}$ ,12 ${alpha}$ ,24,25-pentol, in human urine

Mizuho Une^a, Shinji Takenaka^a, Taiju Kuramoto^a, Kingo Fujimura^a, Takahiko Hoshita^b, and Kenji Kihira^c
^a Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Minami-ku, Hiroshima, Japan
^b Hiroshima International University, Hiroshima, Japan
^c Department of Pharmaceutical Services, Hiroshima University Hospital, Hiroshima, Japan

Correspondence to: Mizuho Une

The stereochemistry at C-24 and C-25 of 27-nor-5ß-cholestane-3 ${alpha}$ ,7 ${alpha}$ ,12 ${alpha}$ ,24,25-pentol,a principal bile alcohol in human urine, and its biosynthesisare studied. Four stereoisomers of the C₂₆-24,25-pentols weresynthesized by reduction with LiAlH₄ of the corresponding epoxidesprepared from (24S)- or (24R)-27-nor-5ß-cholest-25-ene-3 ${alpha}$ ,7 ${alpha}$ ,12 ${alpha}$ ,24-tetrol. The stereochemistries at C-25 were deduced bycomparison of the C₂₆-24,25-pentols with the oxidation productsof (24Z)-27-nor-5ß-cholest-24-ene-3 ${alpha}$ ,7 ${alpha}$ ,12 ${alpha}$ -triol with osmiumtetraoxide. On the basis of this assignment, the principal bilealcohol excreted into human and rat urine was determined tobe (24S,25R)-27-nor-5ß-cholestane-3 ${alpha}$ ,7 ${alpha}$ ,12 ${alpha}$ ,24,25-pentol,accompanied by a lesser amount of (24R,25R)-isomer. To elucidatethe biosynthesis of the C₂₆-24,25-pentol, a putative intermediate,3 ${alpha}$ ,7 ${alpha}$ ,12 ${alpha}$ -trihydroxy-27-nor-5ß-cholestan-24-one, derivedfrom 3 ${alpha}$ ,7 ${alpha}$ , 12 ${alpha}$ -trihydroxy-24-oxo-5ß-cholestanoic acid bydecarboxylation during the side-chain oxidation of 3 ${alpha}$ ,7 ${alpha}$ ,12 ${alpha}$ -trihydroxy-5ß-cholestanoicacid, was incubated with rat liver homogenates. The 24-oxo-bilealcohol could be efficiently reduced to yield mainly (24R)-27-nor-5ß-cholestane-3 ${alpha}$ ,7 ${alpha}$ ,12 ${alpha}$ ,24-tetrol.If a 25R-hydroxylation of the latter steroid occurs, it shouldlead to formation of (24S,25R)-C₂₆-24,25-pentol.

Now it has appeared that a major bile alcohol excreted intohuman urine is (24S,25R)-27-nor-5ß-cholestane-3 ${alpha}$ ,7 ${alpha}$ ,12 ${alpha}$ ,24,25-pentol, which might be derived from 3 ${alpha}$ ,7 ${alpha}$ ,12 ${alpha}$ -trihydroxy-27-nor-5ß-cholestan-24-onevia (24R)-27-nor-5ß-cholestane-3 ${alpha}$ , 7 ${alpha}$ ,12 ${alpha}$ ,24-tetrol.—Une,M., S. Takenaka, T. Kuramoto, K. Fujimura, T. Hoshita, and K.Kihira. Structural and biosynthetic studies of a principal bilealcohol, 27-nor-5ß-cholestane-3 ${alpha}$ ,7 ${alpha}$ ,12 ${alpha}$ ,24,25-pentol, inhuman urine. J. Lipid Res. 2000. 41: 1562;–1567.

Supplementary key words: bile alcohol, bile acid, absolute configuration, human urine,cholesterol, biosynthesis, hydroxylation

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Original Article

Structural and biosynthetic studies of a principal bile alcohol, 27-nor-5ß-cholestane-3,7,12,24,25-pentol, in human urine

Structural and biosynthetic studies of a principal bile alcohol, 27-nor-5ß-cholestane-3 ${alpha}$ ,7 ${alpha}$ ,12 ${alpha}$ ,24,25-pentol, in human urine