|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / EGO|
crystal structures of ferrous and ferrous-no forms of verdoheme in a complex with human heme oxygenase-1: catalytic implications for heme cleavage
Heme oxygenase or haem oxygenase (HO) is an enzyme that catalyzes the degradation of heme. This produces biliverdin, ferrous iron, and carbon monoxide. There is limited evidence that levels of heme oxygenase are positive predictors of metabolic disease, insulin resistance, and metaflammation.
Heme oxygenase cleaves the heme ring at the alpha-methene bridge to form either biliverdin or, if the heme is still attached to a globin, verdoglobin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase.
The reaction occurs as follows:
This reaction can occur in virtually every cell; the classic example is the formation of a bruise, which goes through different colors as it gradually heals: red heme to green biliverdin to yellow bilirubin. Under normal physiological conditions, the activity of heme oxygenase is highest in the spleen, where old erythrocytes are sequestrated and destroyed. In terms of molecular mechanisms, the enzyme facilitates the intramolecular hydroxylation of one meso carbon centre in the heme.
Three isoforms of heme oxygenase are known. Heme oxygenase 1 (HO-1) is an inducible isoform in response to stress such as oxidative stress, hypoxia, heavy metals, cytokines, etc. Heme oxygenase 2 (HO-2) is a constitutive isoform that is expressed under homeostatic conditions. Both HO-1 and HO-2 are ubiquitously expressed and catalytically active.
A third heme oxygenase (HO-3) is not catalytically active, but is thought to work in oxygen sensing.
Roles in physiology
Heme oxygenase expression is induced by oxidative stress, and in animal models increasing this expression seems to be protective. Carbon monoxide released from heme oxygenase reactions can influence vascular tone independently or influence the function of nitric oxide synthase. Carbon monoxide released from the reaction of free heme in the bloodstream of someone with the sickle-cell trait is believed to lessen the effects of cerebral malaria.
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