Stimulation by endozepine of the side-chain cleavage of cholesterol in a reconstituted enzyme system.
Addition of endozepine in nanomolar concentrations to a system for side-chain cleavage reconstituted from highly purified P-450scc and electron carriers (adrenodoxin reductase and adrenodoxin) stimulates the conversion of cholesterol to pregnenolone (side-chain cleavage). This response is concentration and time-dependent and specific to the extent that a second steroidogenic P-450 located in the inner mitochondrial membrane (ie 11 beta-hydroxylase) was not stimulated by endozepine. Homogeneous endozepine prepared from bovine brain, the corresponding genetically engineered peptide and des(glu-ilu)-endozepine isolated from bovine adrenal cortex are all approximately equipotent in this system. Moreover, endozepine accelerates the rate of reduction of P-450scc by NADPH and the electron carriers. The results suggest that endozepine acts directly on P-450 and hence the rate of side-chain cleavage.
Brown
A S
AS
Department of Endocrinology, Prince of Wales Hospital, Randwick, NSW, Australia.
Hall
P F
PF
D000302:Adrenal Cortex / Q000502:physiology; D000818:Animals; D001921:Brain; D002417:Cattle; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism*; D026261:Diazepam Binding Inhibitor; D007700:Kinetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011994:Recombinant Proteins / Q000494:pharmacology
D026261:Diazepam Binding Inhibitor; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D002786:Cholesterol Side-Chain Cleavage Enzyme