P-450 Oxygenases in Lipid Transformation

Minor J. Coon, Dennis R. Koop

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Cytochrome P-450 was first recognized as a pigment in liver microsomes from the absorption peak of its carbon monoxide complex at 450 nm. This CO-binding pigment is found to be a cytochrome of the b type, which is reducible by both NADPH and NADH under anaerobic conditions and is rapidly reoxidizable in the presence of molecular oxygen. The photochemical action spectrum for the reversal of carbon monoxide inhibition of steroid and drug hydroxylation was shown to have a maximum at 450 nm. In contrast to the hepatic cytochromes, which are generally not substrate-specific, the P-450's found in microsomes and mitochondria from endocrine tissues have a much greater selectivity in steroid transformations. The enzyme is also found in plants and in microorganisms, the best studied example being P-450cam, the cytochrome induced by growth of Pseudomonas putida on camphor. P-450cam, which is obtained in a monomeric, soluble state from this organism, has been purified to homogeneity, crystallized, and thoroughly characterized. In the microsomal systems, electron transfer occurs directly from NADPH-cytochrome P-450 reductase to the cytochrome, whereas in the mitochondria1and bacterial systems the reductase contains a single flavin group, and an iron-sulfur protein serves as the direct donor. The P-450's that are involved in the biosynthesis of steroid hormones, bile acids, and the active forms of vitamin D3 exhibit a high degree of substrate and regiospecificity. The steroid hormone-synthesizing enzymes involved in the production of mammalian hormones are of both mitochondria1 and microsomal origin and are distributed in various tissues—including adrenal cortex, ovary, testis, and placenta.

Original languageEnglish (US)
Pages (from-to)645-677
Number of pages33
JournalEnzymes
Volume16
Issue numberC
DOIs
StatePublished - Jan 1 1983

ASJC Scopus subject areas

  • Biotechnology
  • Biophysics
  • Biochemistry
  • Molecular Biology

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