Standard Article

Iron: Heme Proteins, Mono- & Dioxygenases

  1. Luet-Lok Wong,
  2. Stephen G. Bell

Published Online: 15 MAR 2006

DOI: 10.1002/0470862106.ia105

Encyclopedia of Inorganic Chemistry

Encyclopedia of Inorganic Chemistry

How to Cite

Wong, L.-L. and Bell, S. G. 2006. Iron: Heme Proteins, Mono- & Dioxygenases . Encyclopedia of Inorganic Chemistry. .

Author Information

  1. University of Oxford, Oxford, UK

Publication History

  1. Published Online: 15 MAR 2006


Heme (iron protoporphyrin IX) proteins and enzymes play crucial roles in all living organisms. Iron is very tightly bound to the porphyrin and does not dissociate under physiological conditions. Indeed the heme group is almost like a separate element altogether. It is redox-active, and heme proteins such as cytochrome c have important electron-transfer functions. The strong π donor nature of heme iron(II) also means that heme proteins are involved in the binding and activation of small molecules such as oxygen. The P450 heme monooxygenases use two electrons and two protons to activate O2, giving one molecule of water and a high-valent iron-oxo intermediate that is sufficiently reactive to attack aliphatic C[BOND]H bonds in a diverse range of organic molecules. The heme dioxygenases, as the name implies, insert both oxygen atoms of the O2 molecule into the substrate. The known heme dioxygenases are indoleamine ring cleavage enzymes but have not been studied in detail, and no crystal structure of the enzymes is available. It is known that the active form of the enzyme has Fe(II), and that both oxygen and superoxide could be the source of the two oxygen atoms inserted into substrates. The main focus of this article is on the cytochrome P450 monooxygenases.

The P450 (CYP) superfamily of enzymes is found in virtually all organisms where they catalyze the oxidation of endogenous and exogenous organic compounds. These reactions are vital steps in the biosynthesis of steroids and other hormones, and the detoxification and oxidative removal of xenobiotics. The primary activity of P450 enzymes is C[BOND]H bond oxidation, but other activities such as alkene epoxidation, C[BOND]C bond cleavage, heteroatom oxidation, and even reductive reactions are known. These reactions and their mechanisms are surveyed. The major sections review and summarize the steps in the P450 catalytic cycle, the nature of the rate-limiting step, the chemical properties and electronic structure of the heme in the intermediates, and the mechanism of C[BOND]H bond oxidation. The unique activity of P450 enzymes does not arise solely from the heme group; the pivotal roles of the protein environment and dynamics are discussed. The mechanism of aliphatic C[BOND]H bond oxidation is one of the great challenges in chemistry. The nature of the active intermediate in P450 catalysis and the mechanism of action remain controversial. The results of mechanistic and theoretical approaches are brought together and reviewed.


  • P450;
  • CYP;
  • monooxygenases;
  • dioxygenases;
  • heme enzymes;
  • radical rebound mechanism;
  • compound I;
  • ferryl;
  • reductase;
  • ferredoxin;
  • C[BOND]H bond oxidation