In the past decade there has been considerable progress in the characterization of individual human P450 enzymes. These advances were initiated by early work on the purification of individual enzymes from human liver and other sources. The early work in the area was guided by a focus on the most abundant and easily purified enzymes.1–4It is now apparent, in retrospect, that these proteins were in the 2C and 3A families. Efforts were shifted to attempts to purify individual P450s on the basis of catalytic activities with the evidence that in some cases a single P450 could be identified in this way; e.g., the P450 now known as P450 2D6 was found to be under monogenic control. 5 The approach is technically demanding because of the need to do separations in the presence of detergents and then remove them before analysis of catalytic activity. Nevertheless, human P450s 1A1,6 1A2,7 2A6,8 2C8,9 2C9,9,10 2D67,11,12 2E1 13,14 3A4,15 3A5,16 4A11,17 and lanosterol 14α-demethylase18 were isolated in this general manner. Another approach that has been used, sometimes in a mode complementary to catalytic specificity, is purification on the basis of immunochemical similarity to animal P450s. 7,11,19,20

Human Cytochrome P450 Enzymes

Regulation of Aldosterone Biosynthesis

Zonal distribution of aldosterone synthase cytochrome P-450 and cytochrome P-45011 beta in rat adrenocortex was investigated immunochemically using specific antibodies to these enzymes. Localization of aldosterone synthase cytochrome P-450 (cytochrome P-450aldo), a recently identified enzyme that converts deoxycorticosterone to aldosterone in rat adrenocortex was strictly confined to two or three outermost cell layers in the zona glomerulosa. In contrast, cytochrome P-45011 beta, which forms corticosterone, but not aldosterone, from deoxycorticosterone, was localized in the zona fasciculata-reticularis and not in the zona glomerulosa. Neither enzyme was detected in the medulla or the capsule. The functional zonation of adrenocortex with respect to aldosterone and corticosterone syntheses is, thus, ascribable to the localization of cytochromes P-450aldo and P-45011 beta in the respective zones. When rats were maintained under Na-depleted conditions for 10 days, the zona glomerulosa cells containing cytochr...

Zone-specific expression of aldosterone synthase cytochrome P-450 and cytochrome P-45011 beta in rat adrenal cortex: histochemical basis for the functional zonation.

J. Müller

Papers

Aldosterone biosynthesis and cytochrome P-45011 beta: evidence for two different forms of the enzyme in rats.