HMOX2 Human

HO-2 is a microsomal enzyme that catalyzes the degradation of heme to biliverdin, carbon monoxide (CO), and free iron. This process involves the cleavage of the heme ring at the alpha-methene bridge, resulting in the formation of biliverdin, which is subsequently converted to bilirubin by biliverdin reductase . The production of CO, a gaseous signaling molecule, is also a significant aspect of HO-2’s function .

HO-2 is expressed under homeostatic conditions and is not typically induced by stress, unlike its isoform, Heme Oxygenase-1 (HO-1). The enzyme is particularly abundant in the brain, where it is involved in neuroprotection and the regulation of vascular tone .

Recombinant human HO-2 has been successfully expressed in Escherichia coli. This recombinant form retains the ability to accept electrons from NADPH-cytochrome P-450 reductase and exhibits enzymatic activity for the conversion of heme to biliverdin . The recombinant enzyme has been used in various studies to understand its structure-function relationships and catalytic mechanisms .

The catalytic mechanism of HO-2 involves the binding of heme to the enzyme, forming a substrate-enzyme complex. Spectroscopic studies have shown that the ferric heme in the HO-2 complex can exist in different spin states depending on the pH . The reaction with hydrogen peroxide converts the heme into a verdoheme-like intermediate, while the reaction with m-chloroperbenzoic acid yields an oxoferryl species . These properties are similar to those observed in HO-1, suggesting a conserved catalytic mechanism between the two isoforms .

HO-2 has significant implications in pharmacological research due to its role in heme degradation and gas sensing. The enzyme’s activity can be modulated by various compounds, including menadione and its analogs, which selectively activate HO-2 without affecting HO-1 . This selective activation has potential therapeutic applications, particularly in conditions where modulation of heme metabolism and CO production is beneficial .