Glucuronidation of 6 alpha-hydroxy bile acids by human liver microsomes.
The glucuronidation of 6-hydroxylated bile acids by human liver microsomes has been studied in vitro; for comparison, several major bile acids lacking a 6-hydroxyl group were also investigated. Glucuronidation rates for 6 alpha-hydroxylated bile acids were 10-20 times higher than those of substrates lacking a hydroxyl group in position 6. The highest rates measured were for hyodeoxy- and hyocholic acids, and kinetic analyses were carried out using these substrates. Rigorous product identification by high-field proton nuclear magnetic resonance and by electron impact mass spectrometry of methyl ester/peracetate derivatives revealed that 6-O-beta-D-glucuronides were the exclusive products formed in these enzymatic reactions. These results, together with literature data, indicate that 6 alpha-hydroxylation followed by 6-O-glucuronidation constitutes an alternative route of excretion of toxic hydrophobic bile acids.
D000328:Adult; D000368:Aged; D001647:Bile Acids and Salts / Q000378:metabolism*; D002675:Child, Preschool; D002793:Cholic Acids / Q000378:metabolism; D003840:Deoxycholic Acid / Q000378:metabolism; D005260:Female; D005965:Glucuronates / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000201:enzymology*; D013379:Substrate Specificity
D001647:Bile Acids and Salts; D002793:Cholic Acids; D005965:Glucuronates; D003840:Deoxycholic Acid; C004821:muricholic acid; C010471:hyodeoxycholic acid; D014453:Glucuronosyltransferase