Aldosterone synthase cytochrome P-450 expressed in the adrenals of patients with primary aldosteronism.
A human cytochrome P-450 with aldosterone synthase activity was purified from the mitochondria of an aldosterone-producing adenoma. It was recognized by an anti-bovine cytochrome P-450(11 beta) IgG and by a specific antibody raised against a portion of the CYP11B2 gene product, one of the two putative proteins encoded by human cytochrome P-450(11 beta)-related genes (Mornet, E., Dupont, J., Vitek, A., and White, P. C. (1989) J. Biol. Chem. 264, 20961-20967). A similar and probably the same aldosterone synthase cytochrome P-450 was detected in the adrenal of a patient with idiopathic hyperaldosteronism. These aldosterone synthases were distinguishable from cytochrome P-450(11 beta), the product of another cytochrome P-450(11 beta)-related gene, i.e. CYP11B1, by their catalytic, molecular, and immunological properties and also by their localization. The latter enzyme was unable to produce aldosterone and did not react with the specific antibody against the CYP11B2 gene product. It was present both in tumor and non-tumor portions of the adrenals carrying the adenoma and in normal adrenal cortex. On the other hand, aldosterone synthase cytochrome P-450 localized in the tumor portions of the adrenals or in the adrenal of a patient with idiopathic hyperaldosteronism. Thus aldosterone synthase cytochrome P-450, a distinct species from cytochrome P-450(11 beta), is responsible for the biosynthesis of aldosterone in the human, at least in patients suffering from primary aldosteronism.
Ogishima
T
T
Department of Biochemistry, School of Medicine, Keio University, Tokyo, Japan.
Shibata
H
H
Shimada
H
H
Mitani
F
F
Suzuki
H
H
Saruta
T
T
Ishimura
Y
Y
D000236:Adenoma / Q000201:enzymology; D000310:Adrenal Gland Neoplasms / Q000201:enzymology*; D000311:Adrenal Glands / Q000201:enzymology*; D000595:Amino Acid Sequence; D003480:Cushing Syndrome / Q000201:enzymology; D019405:Cytochrome P-450 CYP11B2; D003577:Cytochrome P-450 Enzyme System / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D006929:Hyperaldosteronism / Q000201:enzymology*; D007106:Immune Sera; D015151:Immunoblotting; D007700:Kinetics; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009842:Oligopeptides / Q000138:chemical synthesis; D010673:Pheochromocytoma / Q000201:enzymology; D013250:Steroid Hydroxylases / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*
D007106:Immune Sera; D009842:Oligopeptides; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D019405:Cytochrome P-450 CYP11B2