PMID: 3094584Nov 14, 1986Paper

Competitive inhibitors of rabbit hepatic microsomal steroid 12 alpha-hydroxylase

Biochimica Et Biophysica Acta
M J Joyce, W H Elliott

Abstract

The sterols 7 alpha-hydroxycholest-4-en-3-one (I) and 5 alpha-cholestane-3 alpha,7 alpha-diol (II) are competitive inhibitors for rabbit hepatic microsomal preparations of steroid 12 alpha-hydroxylase with apparent Ki values of 56 and 93 microM, respectively. To ascertain the optimum structure for a substrate with maximal enzymic activity, nine sterols or steroidal acids containing the 7 alpha-hydroxy-4-en-3-one or 3 alpha,7 alpha-dihydroxy-5 alpha configuration were prepared and studied as inhibitors with enzyme preparations in the presence of NADPH, oxygen and appropriate cofactors. Although each of these compounds exhibited competitive inhibition, the best inhibitor for sterol (I) was 7 alpha,25-dihydroxycholest-4-en-3-one (IV) (Ki 36 microM). Steroidal acids (3-oxo-7 alpha-hydroxychol-4-enoic acid and 3-oxo-7 alpha-hydroxy-4-cholene-24-carboxylic acid) were poor inhibitors (Ki 1080 and 654 microM, respectively). For sterol (II) the best inhibitors were sterol (IV) (Ki 35 microM) and 5 alpha-cholestane-3 alpha,7 alpha,25-triol (VIII) (Ki 45 microM). The 12 alpha-hydroxylated products of sterols (I) and (IV) were less tightly bound to the enzyme (Ki 88 and 98 microM, respectively) in the presence of sterol (II). Allochenodeox...Continue Reading

References

Jan 1, 1975·Annual Review of Biochemistry·H Danielsson, J Sjövall
Jan 1, 1985·Preparative Biochemistry·M Y Wang, W H Elliott
May 1, 1974·Proceedings of the Society for Experimental Biology and Medicine·R J BlaskiewiczW H Elliott
Jan 1, 1967·Acta Chemica Scandinavica·A Kallner
Aug 11, 2004·Langmuir : the ACS Journal of Surfaces and Colloids·J PenfoldR K Thomas
Feb 9, 2007·Proceedings of the National Academy of Sciences of the United States of America·Yehuda ChowersJusten H Passwell

Citations

Jan 1, 1989·Free Radical Biology & Medicine·L L Smith, B H Johnson
Nov 14, 2003·Canadian Journal of Physiology and Pharmacology·Maâmar SouidiClaude Lutton

Related Concepts

Chromatography
Microsomes, Liver
Steroid Hydroxylases
Sterol 12-alpha-Hydroxylase
Sterols
Substrate Specificity

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