The heme oxygenase system: a regulator of second messenger gases

Annu Rev Pharmacol Toxicol. 1997;37:517-54. doi: 10.1146/annurev.pharmtox.37.1.517.


The heme oxygenase (HO) system consists of two forms identified to date: the oxidative stress-inducible protein HO-1 (HSP32) and the constitutive isozyme HO-2. These proteins, which are different gene products, have little in common in primary structure, regulation, or tissue distribution. Both, however, catalyze oxidation of heme to biologically active molecules: iron, a gene regulator; biliverdin, an antioxidant; and carbon monoxide, a heme ligand. Finding the impressive heme-degrading activity of brain led to the suggestion that "HO in brain has functions aside from heme degradation" and to subsequent exploration of carbon monoxide as a promising and potentially significant messenger molecule. There is much parallelism between the biological actions and functions of the CO- and NO-generating systems; and their regulation is intimately linked. This review highlights the current information on molecular and biochemical properties of HO-1 and HO-2 and addresses the possible mechanisms for mutual regulatory interactions between the CO- and NO-generating systems.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Carbon Monoxide / metabolism
  • Cardiovascular System / metabolism
  • Heme Oxygenase (Decyclizing) / chemistry
  • Heme Oxygenase (Decyclizing) / metabolism
  • Heme Oxygenase (Decyclizing) / physiology*
  • Heme Oxygenase-1
  • Humans
  • Liver / metabolism
  • Membrane Proteins
  • Nervous System / metabolism
  • Nitric Oxide / metabolism
  • Second Messenger Systems*
  • Tissue Distribution
  • Urogenital System / metabolism


  • Membrane Proteins
  • Nitric Oxide
  • Carbon Monoxide
  • HMOX1 protein, human
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • heme oxygenase-2