Microsomal cytochrome P-450: substrate binding, membrane interactions, and topology.
The microsomal monoxygenase system is of paramount importance for the metabolism of endogenous substrates and xenobiotics. It is capable of detoxifying many compounds, but also activates procarcinogens to carcinogens. Cytochrome P-450 is the terminal enzyme of the monoxygenase system. In this article we briefly review current knowledge of the nature of its active site, its interaction with the membrane, and its topology in the membrane. In contrast to previous proposals there is now strong evidence that cytochrome P-450 spans the membrane with only one short segment. Analysis of tryptophan fluorescence gives further evidence that most of the protein's mass protrudes from the membrane into the cytosolic space.
Vergères
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Laboratory of Biochemistry, Swiss Federal Institute of Technology, Zürich, Switzerland.
Winterhalter
K H
KH
Richter
C
C
D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000493:pharmacokinetics*; D002850:Chromatography, Gel; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism* / Q000502:physiology; D005453:Fluorescence; D050356:Lipid Metabolism; D008862:Microsomes, Liver / Q000201:enzymology*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014364:Tryptophan / Q000378:metabolism
D002273:Carcinogens; D011506:Proteins; D014364:Tryptophan; D003577:Cytochrome P-450 Enzyme System