Steroidogenic electron transport in adrenal cortex mitochondria.
The flavoprotein NADPH-adrenodoxin reductase and the iron sulfur protein adrenodoxin function as a short electron transport chain which donates electrons one-at-a-time to adrenal cortex mitochondrial cytochromes P-450. The soluble adrenodoxin acts as a mobile one-electron shuttle, forming a complex first with NADPH-reduced adrenodoxin reductase from which it accepts an electron, then dissociating, and finally reassociating with and donating an electron to the membrane-bound cytochrome P-450 (Fig. 9). Dissociation and reassociation with flavoprotein then allows a second cycle of electron transfers. A complex set of factors govern the sequential protein-protein interactions which comprise this adrenodoxin shuttle mechanism; among these factors, reduction of the iron sulfur center by the flavin weakens the adrenodoxin-adrenodoxin reductase interaction, thus promoting dissociation of this complex to yield free reduced adrenodoxin. Substrate (cholesterol) binding to cytochrome P-450scc both promotes the binding of the free adrenodoxin to the cytochrome, and alters the oxidation-reduction potential of the heme so as to favor reduction by adrenodoxin. The cholesterol binding site on cytochrome P-450scc appears to be in direct communication with the hydrophobic phospholipid milieu in which this substrate is dissolved. Specific effects of both phospholipid headgroups and fatty acyl side-chains regulate the interaction of cholesterol with its binding side. Cardiolipin is an extremely potent positive effector for cholesterol binding, and evidence supports the existence of a specific effector lipid binding site on cytochrome P.450scc to which this phospholipid binds.
D000302:Adrenal Cortex / Q000378:metabolism*; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000325:Adrenodoxin / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004579:Electron Transport; D005287:Ferredoxin-NADP Reductase / Q000378:metabolism; D005292:Ferricyanides / Q000378:metabolism; D005415:Flavins / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D011485:Protein Binding; D013455:Sulfur / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D005292:Ferricyanides; D005415:Flavins; D008563:Membrane Lipids; D000325:Adrenodoxin; D009249:NADP; D013455:Sulfur; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D007501:Iron; D005287:Ferredoxin-NADP Reductase