title: Synthesis and metabolism of sodium 3 alpha,7 alpha-dihydroxy-25,26-bishomo-5 beta-cholane-26-sulfonate in the hamster.
abstract: This paper reports the chemical synthesis of a new bile acid analogue, namely sodium 3 alpha,7 alpha-dihydroxy-25,26-bishomo-5 beta-cholane-26-sulfonate (bishomoCDC-sul) from chenodeoxycholic acid and describes its metabolism in the hamster. The structure of the new compound was confirmed by proton and carbon-13 nuclear magnetic resonance spectroscopy. After intravenous infusion of [3H]-labeled sulfonate into bile fistula hamsters, it was extracted by the liver and secreted into the bile; more than 65% of the radioactivity was recovered in the bile within 1 h. Following intraduodenal administration of the [3H]sulfonate and [14C]chenodeoxycholyltaurine, both compounds were excreted into the bile more slowly; only 41 and 43% of the radioactivity, respectively, were recovered in the bile during the four-hour experimental period. In contrast, when the labeled compounds were injected into the terminal ileum, both the sulfonate and chenodeoxycholyltaurine were rapidly absorbed and secreted into the bile; 84 and 97%, respectively, of the radioactivity were recovered during a four-hour period. Chromatographic analysis demonstrated that in these short-term experiments most (> 95%) of the sulfonate was secreted into the bile without biotransformation regardless of the route of administration. When infused intravenously at increasing doses, bishomoCDC-sul induced cholestasis at an infusion rate of 1 mumol/min/kg. These results suggest that sodium 3 alpha,7 alpha-dihydroxy-25,26-bishomo-5 beta-cholane-26-sulfonate was absorbed from the terminal ileum by active transport, extracted by the liver, and secreted into the bile in a manner similar to that of the natural bile acids.
authors.affiliation: Department of Surgery, Beth Israel Medical Center, New York, NY 10003, USA.
authors.forename: T
authors.initials: T
authors.lastname: Mikami
authors.forename: E H
authors.initials: EH
authors.lastname: Mosbach
authors.forename: B I
authors.initials: BI
authors.lastname: Cohen
authors.forename: N
authors.initials: N
authors.lastname: Ayyad
authors.forename: M
authors.initials: M
authors.lastname: Yoshii
authors.forename: K
authors.initials: K
authors.lastname: Kihira
authors.forename: T
authors.initials: T
authors.lastname: Hoshita
mesh_terms: D000818:Animals; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D002779:Cholestasis / Q000503:physiopathology*; D006224:Cricetinae; D005999:Glycochenodeoxycholic Acid / Q000737:chemistry; D007408:Intestinal Absorption; D008099:Liver / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D015394:Molecular Structure
chemical_list: C093669:3,7-dihydroxy-25,26-bishomocholane-26-sulfonate; D002635:Chenodeoxycholic Acid; D005999:Glycochenodeoxycholic Acid