Heme oxygenase

Heme oxygenase, or haem oxygenase, (HMOX, commonly abbreviated as HO) is an enzyme that catalyzes the degradation of heme to produce biliverdin, ferrous iron, and carbon monoxide.

There are many heme degrading enzymes in nature. In general, only aerobic heme degrading enzymes are referred to as HMOX-like enzymes whereas anaerobic enzymes are typically not affiliated with the HMOX family.

Heme oxygenase (alternatively spelled using haem or oxidase) catalyzes the degradation of heme to biliverdin/bilirubin, ferrous ion, and carbon monoxide. The human genome may encode three isoforms of HMOX.

The degradation of heme forms three distinct chromogens as seen in healing cycle of a bruise. This reaction can occur in virtually every cell and platelet; the classic example is the healing process of a contusion, which forms different chromogens as it gradually heals: (red) heme to (green) biliverdin to (yellow) bilirubin which is widely known for jaundice. In general, aside from sharing the functionality of catabolizing heme, all HMOX isoforms share are signature 24-residue sequence considered to be essential for the enzymatic activity.

Though present throughout the body, HMOX is most active in the spleen facilitating degradation of hemoglobin during erythrocyte recycling (approximately 0.8% of the erythrocyte pool per day).

Heme oxygenase 1 (HMOX1, commonly HO-1) is a member of the heat shock protein (HSP) family identified as HSP32. HO-1 is a 32kDa enzyme which contains 288 amino acid residues encoded by the HMOX1 gene. HO-1 is not a hemoprotein as it does not contain any heme prosthetic groups. The activity of HO-1 is dependent upon NADPH-Cytochrome P450 Reductase.

HO-1 is a stress-induced isoform present throughout the body with highest concentrations in the spleen, liver, and kidneys, and on the cellular level is primarily located in the endoplasmic reticulum, although it has also been reported in the mitochondria, cell nucleus, and plasma membrane. Soluble variations of HO-1 have been described. HO-1 may also serve as a chaperone protein, engage in protein-protein interactions, be secreted into the extracellular space, and participate in other cellular functions beyond its catalytic activity. HO-1 may also generate small amounts of carbon suboxide. HO-1 enzymes are degraded via ubiquitination.

The enzyme has been the subject of extensive investigation into its regulatory signaling, immunomodulatory, and cryoprotective roles. HMOX1 is an essential enzyme. Human HMOX1-deficiency is rare, however several cases have been reported which generally results in death.