hemeoxygenase

Heme oxygenase is a microsomal enzyme that catalyzes the first step in heme degradation. It converts heme to biliverdin, releasing iron and carbon monoxide in a reaction that consumes oxygen and NADPH. The enzyme is present in many tissues and plays a central role in heme turnover and cellular protection against stress.

There are two main isoforms in mammals: heme oxygenase-1 (HO-1) and heme oxygenase-2 (HO-2). HO-1 is inducible and responds to various stressors such as oxidative stress, heme overload, heat shock, and inflammation. HO-2 is constitutively expressed and found in tissues including the brain and testes, contributing to baseline heme metabolism.

The biochemical reaction involves heme, oxygen, and reducing equivalents to produce biliverdin, ferrous iron, and carbon monoxide; biliverdin is subsequently reduced to bilirubin by biliverdin reductase. Biliverdin and bilirubin possess antioxidant properties, while carbon monoxide can act as a signaling molecule involved in vasodilation and anti-inflammatory pathways.

Genetically, the enzymes are encoded by the HMOX1 and HMOX2 genes, which produce HO-1 and HO-2, respectively. Regulation of HO-1 is sensitive to stress signals, while HO-2 is more stably expressed but can be modulated under certain conditions. The HO system has been implicated in protection against oxidative injury, regulation of vascular tone, iron recycling, and cellular defense mechanisms.

Clinical relevance and research interest focus on the role of heme oxygenase in cardiovascular and neurodegenerative diseases, inflammation, and aging. Pharmacological agents can modulate HO activity, with inhibitors and inducers explored in experimental settings for potential therapeutic applications.