Identification of 17-methyl-18-norandrosta-5,13(17-dien-3beta-ol, the C19 fragment formed by adrenal side chain cleavage of a 20-aryl analog of (20S)-20-hydroxycholesterol.
Incubation of (20R)-20-phenyl-5-pregnene-3beta,20-diol, an aromatic analog of (23S)-20-hydroxycholesterol, with an adrenal mitochondrial preparation leads to the formation of four compounds: pregnenolone, phenol, a C8 ketone, acetophenone, and a nonpolar C19 compound. This latter compound has now been identified by reverse isotope dilution analysis and by gas chromatography/mass spectrometry as 17-methyl-18-norandrosta-5,13(17)-dien-3beta-ol. From these results it is evident that enzymatic fission of the C-17,20 bond of this synthetic derivative occurs. On the other hand, when (20S)-20-hydroxy[21-14C]cholesterol was used as substrate, the analogous cleavage did not take place. Thus, substitution of an aromatic group on C-20 facilitates side chain cleavage between that carbon atom and the nucleus whereas neither of the naturally occuring precursors, cholesterol or its 20-hydroxylated counterpart, are metabolized to a C8 fragment.
D000311:Adrenal Glands / Q000378:metabolism; D000737:Androstenols / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002784:Cholesterol / Q000031:analogs & derivatives*; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D003460:Crystallization; D006888:Hydroxycholesterols / Q000031:analogs & derivatives*; D006914:Hydroxysteroids / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008928:Mitochondria / Q000378:metabolism; D011283:Pregnenes / Q000378:metabolism*
D000737:Androstenols; D006888:Hydroxycholesterols; D006914:Hydroxysteroids; D011283:Pregnenes; D002784:Cholesterol; D002786:Cholesterol Side-Chain Cleavage Enzyme