The BIOSYNTHESIS of estrogens is catalyzed by an enzyme complex termed aromatase which is localized in the endoplasmic reticulum of cells in which it is expressed. The aromatase enzyme complex consists of two components (1): The first is a form of cytochrome P-450 known as aromatase cytochrome P-450 (P-450AROM). This heme protein is responsible for binding the C19 steroid substrate and catalyzing the concerted series of reactions leading to the formation of the phenolic A ring. The second is a flavoprotein, NADPH-cytochrome P-450 reductase, which is an essentially ubiquitous protein in the endoplasmic reticulum of most cell types and is responsible for transferring reducing equivalents from NADPH to cytochrome P-450. Since there is only one gene encoding the reductase, this enzyme must be capable of transferring reducing equivalents to any form of microsomal cytochrome P-450 that it encounters (2). The aromatase reaction apparently utilizes 3 moles oxygen and 3 moles NADPH for every mole of C19 steroid metabolized (3). The first 2 oxygen molecules are utilized in the oxidation of the C19 angular methyl group. Considerable speculation continues as to the site and the mechanism of insertion of the third oxygen molecule. It has been suggested that this third site of oxygen attack is at the 2β-position (4); however, more recent work suggests that peroxidative attack, again involving the C19 methyl group, may be involved instead (5).
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism