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: T Mikami, E H Mosbach, B I Cohen, N Ayyad, M Yoshii, K Kihira, T Hoshita
• Journal: Lipids (Lipids) Vol. 30 Issue 1 Pg. 71-8 (Jan 1995) ISSN: 0024-4201 [Print] United States
• PMID: 7760691 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 3,7-dihydroxy-25,26-bishomocholane-26-sulfonate
• Chenodeoxycholic Acid
• Glycochenodeoxycholic Acid

Topics

• Animals
• Chenodeoxycholic Acid (analogs & derivatives, biosynthesis, chemistry, metabolism)
• Cholestasis (physiopathology)
• Cricetinae
• Glycochenodeoxycholic Acid (chemistry)
• Intestinal Absorption
• Liver (metabolism)
• Male
• Mesocricetus
• Molecular Structure