Heme oxygenase
Heme oxygenase (HO) is an enzyme that breaks down heme, the iron-containing part of hemoglobin. In doing so, it produces three things: biliverdin (which is converted to bilirubin), free iron, and carbon monoxide (CO). This reaction helps recycle iron and protects cells from heme’s potentially harmful effects.
There are three forms of HO in humans:
- HO-1 (HMOX1): Also called heat shock protein 32, HO-1 is induced by stress. It’s a 32-kDa enzyme made of 288 amino acids and works with NADPH–cytochrome P450 reductase. HO-1 is found throughout the body but is especially active in the spleen, liver, and kidneys, mainly in the endoplasmic reticulum. It can do more than just catalyze the reaction, participating in protein interactions and signaling. HO-1 helps protect cells during inflammation, low oxygen, and other stresses. Deficiency in HO-1 is very rare and can be deadly.
- HO-2 (HMOX2): This form is constitutive, meaning it’s always present in certain tissues such as the brain, testes, and the gastrointestinal tract. It’s a related enzyme but is less responsive to stress than HO-1.
- HO-3: A controversial third form that is often considered inactive or not a true catalytic enzyme.
How the reaction works:
HO cleaves the heme ring at a specific position with oxygen, in a three-step process that requires oxygen. The main products—biliverdin (then bilirubin), iron, and CO—play important roles in normal physiology and signaling. The bilirubin and biliverdin have antioxidant properties, and CO can act as a signaling molecule with anti-inflammatory effects. The color changes seen as bruises heal (red heme → green biliverdin → yellow bilirubin) illustrate this pathway.
HO enzymes are found in many organisms, including bacteria and plants. In humans, HO-1 ramps up in response to stress, while HO-2 is more constant. Researchers are exploring drugs that modulate HO-1 and HO-2 for various diseases, but clear clinical benefits are still being studied.
This page was last edited on 3 February 2026, at 01:02 (CET).