Inhibition of Cholesterol Side-chain

  • CLEAVAGE BY 22-AZACHOLESTEROL
  • Published 2002

Abstract

The side-chain of cholesterol is oxidatively cleaved by a cytochrome P-450-dependent enzyme system present in mammalian adrenal mitochondria. The reaction was postulated to proceed via one or more hydroxylated intermediates. Inhibition of the reaction by the potent inhibitor 22-azacholesterol did not result in a build-up of the postulated intermediates: (ZOS)-20-hydroxycholesterol. (22R)-22.hydroxycholesterol, (20R,22R)-20,22-dihydroxycholesterol or (20S)-cholesterol hydroperoxide. Spectral studies indicate a modified type II spectrum for the reaction of 22-azacholesterol with adrenal mitochondrial cytochrome P-450. In addition, spectral and electron spin resonance studies indicate a common interaction of cholesterol and 22-azacholesterol with the cytochrome. Although this study does not resolve the question of the intermediacy of the oxygenated derivatives in the cleavage reaction. it indicates that the binding of 22-azacholesterol depends on its steroid structure rather than on its amine character. A discussion of the proximity of the heme to the substrate binding site is also pre-

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Cite this paper

@inproceedings{22AZACHOLESTEROL2002InhibitionOC, title={Inhibition of Cholesterol Side-chain}, author={CLEAVAGE BY 22-AZACHOLESTEROL}, year={2002} }