The role of cytochrome P-450 in the regulation of steroid biosynthesis.
A cytochrome P-450 from bovine adrenocortical mitochondria has been purified to near homogeneity. The protein catalyzes side-chain cleavage of cholesterol (cholesterol leads to pregnenolone) but neither 11beta- nor 18-hydroxylation. It consists of 16 subunits of two species (MW 52,000) and contains 8 heme groups. The enzyme has been used to determine the stoichiometry of side-chain cleavage with the following results: (TPNH and O2 consumed/mole of cleavage), cholesterol 3:3:1, 20S-hydroxycholesterol 2:2:1 and 20S,22R-dihydroxycholesterol 1:1:1. These findings support the occurrence of the proposed pathway for the side-chain cleavage of cholesterol. Cleavage of the diol is inhibited by CO and shows a characteristic P-450 photochemical action spectrum. Evidently the diol is cleaved in a typical monoxygenase reaction. The active form of the enzyme contains 16 subunits (protein 16); forms consisting of 8 (protein 8) and 4 (protein 4) subunits can be isolated and are enzymatically active only by prior conversion to protein 16.
D000302:Adrenal Cortex / Q000201:enzymology*; D000311:Adrenal Glands / Q000201:enzymology*; D000818:Animals; D002417:Cattle; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000378:metabolism; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006888:Hydroxycholesterols / Q000031:analogs & derivatives* / Q000378:metabolism; D007700:Kinetics; D046911:Macromolecular Substances; D008928:Mitochondria / Q000201:enzymology; D008970:Molecular Weight; D010088:Oxidoreductases / Q000378:metabolism*; D010101:Oxygen Consumption; D011284:Pregnenolone / Q000096:biosynthesis*
D006888:Hydroxycholesterols; D046911:Macromolecular Substances; D011284:Pregnenolone; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D010088:Oxidoreductases; D002786:Cholesterol Side-Chain Cleavage Enzyme