Adrenal P-450scc modulates activity of P-45011 beta in liposomal and mitochondrial membranes. Implication of P-450scc in zone specificity of aldosterone biosynthesis in bovine adrenal.
Bovine adrenal P-45011 beta catalyzes the 11 beta- and 18-hydroxylation of corticosteroids as well as aldosterone synthesis. These activities of P-45011 beta were found to be modulated by another mitochondrial cytochrome P-450 species, P-450scc. The presence together of P-45011 beta and P-450scc in liposomal membranes was found to remarkably stimulate the 11 beta-hydroxylase activity of P-45011 beta and also stimulate the cholesterol desmolase activity of P-450scc. The stimulative effect of P-450scc on 11 beta-hydroxylase activity diminished by the addition of protein-free liposomes to proteoliposomes containing P-45011 beta and P-450scc, thus showing P-450scc to interact with P-45011 beta in the same membranes. Kinetic analysis of this effect indicated the formation of an equimolar complex between P-45011 beta and P-450scc on liposomal membranes. P-45011 beta in the complex had not only stimulated activity for 11 beta- and 18-hydroxylation of 11-deoxycorticosterone but also suppressed activity for production of 18-hydroxycorticosterone and aldosterone. When the inner mitochondrial membranes of zona fasciculata-reticularis from bovine adrenal were treated with anti-P-450scc IgG, aldosterone formation was stimulated to a greater extent than that of zona glomerulosa. This indicates the aldosterone synthesizing activity of P-45011 beta in the zona fasciculata-reticularis to be suppressed by interaction with P-450scc. The zone-specific aldosterone synthesis of P-45011 beta in bovine adrenal may possibly be induced by differences in interactions with P-450scc of mitochondrial membranes in each zone.
Ikushiro
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Faculty of Integrated Arts and Sciences, Hiroshima University, Japan.
Kominami
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Takemori
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D000302:Adrenal Cortex / Q000201:enzymology*; D000325:Adrenodoxin / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism*; D006706:Homeostasis; D007425:Intracellular Membranes / Q000201:enzymology*; D007700:Kinetics; D008081:Liposomes; D008928:Mitochondria / Q000201:enzymology*; D010743:Phospholipids / Q000494:pharmacology; D011510:Proteolipids / Q000378:metabolism*; D013252:Steroid 11-beta-Hydroxylase / Q000378:metabolism*; D013367:Submitochondrial Particles / Q000201:enzymology
D008081:Liposomes; D010743:Phospholipids; D011510:Proteolipids; C020485:proteoliposomes; D000325:Adrenodoxin; D013252:Steroid 11-beta-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme