Cytochrome P450 regulation: the interplay between its heme and apoprotein moieties in synthesis, assembly, repair, and disposal

Abstract

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.

Keywords::

• Heme synthesis
• heme degradation
• P450 inactivation
• P450 transcription
• P450 translation
• P450 repair
• P450 disposal

Acknowledgements

F. De Matteis would like to thank the Royal Society of Edinburgh for an Auber Award.

Declaration of interest

This work was supported by NIH grants DK26506 and GM44037 (to MAC).