Mechanism of intestinal formation of deoxycholic acid from cholic acid in humans: evidence for a 3-oxo-delta 4-steroid intermediate.
12 alpha-Hydroxy-3-oxo-4-cholenoic acid coupled to an adenosine nucleotide has been shown to be a metabolite of cholic acid in the intestinal anaerobic bacteria, Eubacterium species VPI 12708 (1987. J. Biol. Chem. 262: 4701-4707) and it has been suggested that this may be an intermediate in the conversion of cholic acid into deoxycholic acid. The possibility that the intestinal conversion of cholic acid into deoxycholic acid involves a 3-oxo-delta 4-steroid as an intermediate has been studied in the present work by use of [3 beta-3H]- and [5-3H]-labeled cholic acid. Whole cells as well as cell extracts of Eubacterium sp. VPI 12708 catalyzed conversion of [3 beta-3H] + [24-14C]cholic acid into deoxycholic acid with loss of about 50% of 3H label. When unlabeled chenodeoxycholic acid (20 microM) was added along with [3 beta-3] + [24-14C]cholic acid, then approximately 85% of the [3 beta-3H]-labeled was lost from deoxycholic acid. After administration of the same mixture to two healthy volunteers, deoxycholic acid could be isolated that had lost 81 and 84%, respectively, of the 3H label. Conversion of a mixture of [5-3H]- and [24-14C]labeled cholic acid by the above intestinal bacteria or cell extracts led to loss of 79-94 of the [5-3H] label.(ABSTRACT TRUNCATED AT 250 WORDS)
Björkhem
I
I
Department of Clinical Chemistry, Karolinska Institutet, Huddinge Hospital, Sweden.
Einarsson
K
K
Melone
P
P
Hylemon
P
P
D000328:Adult; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D019826:Cholic Acid; D002793:Cholic Acids / Q000138:chemical synthesis / Q000378:metabolism*; D003013:Clostridium / Q000378:metabolism; D003840:Deoxycholic Acid / Q000378:metabolism*; D005051:Eubacterium / Q000378:metabolism; D005260:Female; D006801:Humans; D006868:Hydrolysis; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure
D002793:Cholic Acids; D003840:Deoxycholic Acid; D019826:Cholic Acid