Steroidogenic electron transport in adrenal cortex mitochondria

Mol Cell Biochem. 1982 May 28;45(1):13-31. doi: 10.1007/BF01283159.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adrenal Cortex / metabolism*
  • Adrenal Cortex Hormones / biosynthesis*
  • Adrenodoxin / metabolism
  • Cholesterol / metabolism
  • Cytochrome P-450 Enzyme System / metabolism
  • Electron Transport*
  • Ferredoxin-NADP Reductase / metabolism
  • Ferricyanides / metabolism
  • Flavins / metabolism
  • Intracellular Membranes / metabolism
  • Iron / metabolism
  • Membrane Lipids / metabolism
  • Mitochondria / metabolism*
  • NADP / metabolism
  • Oxidation-Reduction
  • Protein Binding
  • Sulfur / metabolism

Substances

  • Adrenal Cortex Hormones
  • Ferricyanides
  • Flavins
  • Membrane Lipids
  • Adrenodoxin
  • NADP
  • Sulfur
  • Cytochrome P-450 Enzyme System
  • Cholesterol
  • Iron
  • Ferredoxin-NADP Reductase