IUBMB Enzyme Nomenclature

EC 1.17.99.5

Accepted name: bile-acid 7α-dehydroxylase

Reaction: (1) deoxycholate + FAD + H2O = cholate + FADH2
(2) lithocholate + FAD + H2O = chenodeoxycholate + FADH2

For diagram click here and mechanism click here.

Glossary: allodeoxycholate = 3α,12α-dihydroxy-5α-cholan-24-oate cholate = 3α,7α,12α-trihydroxy-5β-cholan-24-oate
chenodeoxycholate = 3α,7α-dihydroxy-5β-cholan-24-oate
deoxycholate = 3α,12α-dihydroxy-5β-cholan-24-oate
lithocholate = 3α-hydroxy-5β-cholan-24-oate

Other name(s): cholate 7α-dehydroxylase; 7α-dehydroxylase; bile acid 7-dehydroxylase; deoxycholate:NAD+ oxidoreductase

Systematic name: deoxycholate:FAD oxidoreductase (7α-dehydroxylating)

Comments: Under physiological conditions, the reactions occur in the reverse direction to that shown above. This enzyme is highly specific for bile-acid substrates and requires a free C-24 carboxy group and an unhindered 7α-hydroxy group on the B-ring of the steroid nucleus for activity, as found in cholate and chenodeoxycholate. The reaction is stimulated by the presence of NAD+ but is inhibited by excess NADH. This unusual regulation by the NAD+/NADH ratio is most likely the result of the intermediates being linked at C-24 by an anhydride bond to the 5'-diphosphate of 3'-phospho-ADP [2,5,6]. Allodeoxycholate is also formed as a side-product of the 7α-dehydroxylation of cholate [6]. The enzyme is present in intestinal anaerobic bacteria [6], even though its products are important in mammalian physiology.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 85130-33-2

References:

1. White, B.A., Cacciapuoti, A.F., Fricke, R.J., Whitehead, T.R., Mosbach, E.H. and Hylemon, P.B. Cofactor requirements for 7α-dehydroxylation of cholic and chenodeoxycholic acid in cell extracts of the intestinal anaerobic bacterium, Eubacterium species V.P.I. 12708. J. Lipid Res. 22 (1981) 891-898. [PMID: 7276750]

2. White, B.A., Paone, D.A., Cacciapuoti, A.F., Fricke, R.J., Mosbach, E.H. and Hylemon, P.B. Regulation of bile acid 7-dehydroxylase activity by NAD+ and NADH in cell extracts of Eubacterium species V.P.I. 12708. J. Lipid Res. 24 (1983) 20-27. [PMID: 6833878]

3. Coleman, J.P., White, W.B. and Hylemon, P.B. Molecular cloning of bile acid 7-dehydroxylase from Eubacterium sp. strain VPI 12708. J. Bacteriol. 169 (1987) 1516-1521. [PMID: 3549693]

4. Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137-174. [PMID: 12543708]

5. Coleman, J.P., White, W.B., Egestad, B., Sjövall, J. and Hylemon, P.B. Biosynthesis of a novel bile acid nucleotide and mechanism of 7α-dehydroxylation by an intestinal Eubacterium species. J. Biol. Chem. 262 (1987) 4701-4707. [PMID: 3558364]

6. Hylemon, P.B., Melone, P.D., Franklund, C.V., Lund, E. and Björkhem, I. Mechanism of intestinal 7α-dehydroxylation of cholic acid: evidence that allo-deoxycholic acid is an inducible side-product. J. Lipid Res. 32 (1991) 89-96. [PMID: 2010697]

[EC 1.17.99.5 created 2005 as EC 1.17.1.6, transferred 2006 to EC 1.17.99.5]


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