Cytochrome P450 regulation: the interplay between its heme and apoprotein moieties in synthesis, assembly, repair, and disposal.
Heme is vital to our aerobic universe. Heme cellular content is finely tuned through an exquisite control of synthesis and degradation. Heme deficiency is deleterious to cells, whereas excess heme is toxic. Most of the cellular heme serves as the prosthetic moiety of functionally diverse hemoproteins, including cytochromes P450 (P450s). In the liver, P450s are its major consumers, with >50% of hepatic heme committed to their synthesis. Prosthetic heme is the sine qua non of P450 catalytic biotransformation of both endo- and xenobiotics. This well-recognized functional role notwithstanding, heme also regulates P450 protein synthesis, assembly, repair, and disposal. These less well-appreciated aspects are reviewed herein.
Correia
Maria Almira
MA
Department of Cellular and Molecular Pharmacology, The Liver Center, University of California, San Francisco, 94158, USA. almira.correia@ucsf.edu
Sinclair
Peter R
PR
De Matteis
Francesco
F
D000818:Animals; D001051:Apoenzymes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D004795:Enzyme Stability; D006418:Heme / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D015394:Molecular Structure; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015533:Transcriptional Activation
D001051:Apoenzymes; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; D017346:Protein Serine-Threonine Kinases