[4] Heme oxygenase 1 (HMOX1, commonly HO-1) is a member of the heat shock protein (HSP) family identified as HSP32.

[6] HO-1 is a stress-induced isoform present throughout the body[7] 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.

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.

[16] Heme oxygenase 2 (HMOX2 or HO-2) is a constitutive isoform that is expressed under homeostatic conditions in the testes, gastrointestinal tract, endothelial cells and the brain.

Commensal microbiota generally have CO tolerance as they produce and respond to CO signals; upon excretion from the microbe, the CO either directly benefits the host or applies selection pressure against pathogens thereby serving as a symbiotic currency.

[21] Although chlorophyll is structurally similar to heme, it is unclear if any HMOX-like enzymes are capable of facilitating metabolism.

Akin to HMOX, coupled oxidation occurs at the alpha-methine bridge and leads to formation of biliverdin although the reaction's stoichiometry is different.

In terms of molecular mechanisms, the enzyme facilitates the intramolecular hydroxylation of one meso carbon centre in the heme.

[26][27] Endogenous inducers include i) lipids such as lipoxin and epoxyeicosatrienoic acid; and ii) peptides such as adrenomedullin and apolipoprotein; and iii) hemin.

[26] NRF2 inducers with downstream HO-1 induction include: genistein, 3-hydroxycoumarin, oleanolic acid, isoliquiritigenin, PEITC, diallyl trisulfide, oltipraz, benfotiamine, auranofin, acetaminophen, nimesulide, paraquat, ethoxyquin, diesel exhaust particles, silica, nanotubes, 15-deoxy-Δ12,14 prostaglandin J2, nitro-oleic acid, hydrogen peroxide, and succinylacetone.

The remaining 20% of heme-derived CO production is attributed to hepatic catabolism of hemoproteins (myoglobin, cytochromes, catalase, peroxidases, soluble guanylate cyclase, nitric oxide synthase) and ineffective erythropoiesis in bone marrow.

[34][35] As a signaling agent, carbon monoxide is involved in normal physiology and has therapeutic benefits in many indications such as ameliorating inflammation and hypoxia.

[33][36] It remain under investigation, however, to what extent HMOX is involved in carbon monoxide's protective effect against hypoxia as 3 molar equivalents of oxygen are required to produce carbon monoxide from heme catabolism, along with the question of heme bioavailability,[37] and slow HMOX1 induction which may take several hours (e.g. the slow healing of a bruise).

[39] In most cases, HMOX selectively cleaves heme (iron protoporphyrin IX) at the α-methine bridge.

Drosophila melanogaster contains a unique HMOX that is not alpha specific resulting in formation of biliverdin IXα, IXβ, IXδ.

[5] Non-enzymatic oxidation of heme is likewise non-specific resulting in ring opening at the α, β, γ, or δ positions.

[43][44] HMOX1 was first characterized by Tenhunen and Rudi Schmid upon demonstrating it as the enzyme responsible for catalyzing biotransformation of heme to bilirubin.

[12] Alexander Gettler confirmed CO to have a normal presence in blood in 1933, however, he attributed the finding to inevitable pollution exposure or perhaps derived from the human microbiome.