Competitive inhibition of side chain oxidation of 3 alpha, 7 alpha-dihydroxy-5 beta-cholestan-26-oic acid by 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestan-26-oic acid in the hamster.
3 alpha,7 alpha-dihydroxy-5 beta-cholestan-26-oic acid (DHCA) and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan-26-oic acid (THCA) are metabolized into chenodeoxycholic acid and cholic acid, respectively, through oxidation and cleavage of the terminal three carbons of the side chain. The present study was designed to determine if the same or different side chain oxidation systems are used by these compounds in the bile fistula hamster model. Although a single injection of [3H]THCA is nearly completely metabolized into cholic acid, only about 50% is converted into cholic acid when THCA is infused at a rate of 0.083 mumol/min. The remainder is excreted in the bile unchanged indicating saturation of the side chain oxidation system. Fifty-nine +/- 1.1% (+/- 1SEM) of a single injection of [3H]DHCA is metabolized into chenodeoxycholic acid in bile fistula hamsters infused with either saline or cholic acid at a rate of 0.083 mumol/min. The remainder was excreted as several other metabolic products including cholic acid. However, when [3H]DHCA was administered during an 0.083 mumol/min infusion of THCA, only 39.0 +/- 4.5% of the radioactivity in bile was identified as chenodeoxycholic acid. Thus, this study indicates that DHCA and THCA share at least one of the enzymes involved in side chain oxidation.
D000818:Animals; D001646:Bile / Q000378:metabolism*; D001667:Binding, Competitive; D002635:Chenodeoxycholic Acid / Q000096:biosynthesis; D002777:Cholestanols / Q000378:metabolism* / Q000494:pharmacology*; D002793:Cholic Acids / Q000096:biosynthesis*; D006224:Cricetinae; D007553:Isotope Labeling; D008297:Male; D008647:Mesocricetus; D014316:Tritium
C000986:3,7-dihydroxycholestan-26-oic acid; D002777:Cholestanols; D002793:Cholic Acids; D002635:Chenodeoxycholic Acid; D014316:Tritium; C022069:3,7,12-trihydroxycholestan-26-oic acid