PT  - JOURNAL ARTICLE
AU  - Lambeth, J D
TI  - 22-Ketocholesterol. A potent competitive inhibitor of cytochrome P-450scc-dependent side-chain cleavage of cholesterol.
DP  - 1983 May 01
TA  - Molecular Pharmacology
PG  - 743--747
VI  - 23
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/23/3/743.short
4100  - http://molpharm.aspetjournals.org/content/23/3/743.full
SO  - Mol Pharmacol1983 May 01; 23
AB  - 22-Ketocholesterol binds with high affinity to purified, phospholipid vesicle-reconstituted cytochrome P-450scc. Binding, quantitated using reversal of cholesterol-induced absorbance changes in the Soret region of the enzyme, indicates an affinity 3-5 times greater than that for the normal substrate cholesterol. The ketosteroid cannot be hydroxylated at position 22 and thus acts as a potent inhibitor of cholesterol side-chain cleavage. Steady-state kinetics demonstrate competitive inhibition by this steroid and provide a KI value several-fold lower than the cholesterol Km. On the basis of recently proposed mechanisms for hydroxylation by cytochromes P-450, 22-ketocholesterol may exert its inhibitory effect by acting as a tightly bound analogue that resembles the enzyme-bound cholesterol from which a hydrogen has been abstracted from position 22.