Deoxycholate 7 alpha-hydroxylase in the hamster: substrate specificity and effect of phenobarbital.
In a recent publication, we reported that deoxycholic acid is 7 alpha-hydroxylated to yield glycocholate or taurocholate in vivo in the hamster (1987. Kuroki et al. Hepatology. 7: 229-234). In order to explore the possibility that amidation of free deoxycholic acid precedes the 7 alpha-hydroxylation, we assayed 7 alpha-hydroxylase activities of free and conjugated deoxycholates in vitro. 7 alpha-Hydroxylase activities of glycodeoxycholate and taurodeoxycholate were 720 +/- 132 and 640 +/- 160 pmol/mg.min-1, respectively. Activity of 7 alpha-hydroxylation of free deoxycholate was very low (60 +/- 20 pmol/mg.min-1). After treatment with phenobarbital in a dose of 100 mg/kg per day for 6 days, 7 alpha-hydroxylase activities of conjugated deoxycholates were decreased significantly (40%, P less than 0.01, n = 8), whereas that of free deoxycholate was not significantly changed. In the rat, 7 alpha-hydroxylase activities of conjugated deoxycholates were induced significantly (45% increase, P less than 0.05, n = 5) by phenobarbital treatment in sharp contrast to the hamster. There were significant correlations between the 7 alpha-hydroxylase activity of taurodeoxycholate and that of glycodeoxycholate both in the hamster and in the rat (hamsters: n = 16, r = 0.98, P less than 0.01; rats: n = 10, r = 0.82, P less than 0.01). These studies suggested that deoxycholic acid is 7 alpha-hydroxylated after amidation with glycine or taurine in vivo and that the same enzyme may well catalyze the 7 alpha-hydroxylation of glycodeoxycholate and taurodeoxycholate in the hamster.(ABSTRACT TRUNCATED AT 250 WORDS)
Yamashita
H
H
Department of Surgery I, Kyushu University Faculty of Medicine, Fukuoka, Japan.
Kuroki
S
S
Nakayama
F
F
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase; D006224:Cricetinae; D003840:Deoxycholic Acid / Q000378:metabolism; D005260:Female; D008297:Male; D008647:Mesocricetus; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013379:Substrate Specificity
D001647:Bile Acids and Salts; D003840:Deoxycholic Acid; D013250:Steroid Hydroxylases; D002790:Cholesterol 7-alpha-Hydroxylase; C292712:deoxycholate 7-alpha-hydroxylase; D010634:Phenobarbital