Haemopexin

Haemopexin (also spelled hemeopexin or abbreviated as HPX) is a glycoprotein that in humans is encoded by the HPX gene. Haemopexin is primarily known for its ability to bind heme with the highest affinity of any known protein, a function that is critical in the body's management of free heme levels. Free heme is a potentially toxic substance that can catalyze the formation of reactive oxygen species, leading to cellular damage and oxidative stress. By binding free heme, haemopexin prevents these harmful effects and facilitates the safe transport of heme to the liver, where it can be degraded and recycled.

Function

Haemopexin plays a crucial role in heme metabolism. When red blood cells are lysed, heme is released into the bloodstream. The body must efficiently manage this free heme to prevent oxidative damage. Haemopexin binds to free heme with high affinity, forming a stable complex that is recognized and taken up by liver cells via receptor-mediated endocytosis. Once inside the liver cell, heme is released from haemopexin and is subsequently catabolized by heme oxygenase, leading to the production of biliverdin, iron, and carbon monoxide.

Structure

Haemopexin is a single-chain glycoprotein with a molecular weight of approximately 60 kDa. It is composed of two similar domains that form a deep cleft, which is the binding site for heme. The protein is heavily glycosylated, which is important for its stability and solubility in plasma.

Clinical Significance

Levels of haemopexin in the blood plasma can be affected by various conditions. Low levels of haemopexin can be observed in diseases associated with increased hemolysis, such as sickle cell anemia and thalassemia, because the capacity of haemopexin to bind heme is exceeded. Additionally, haemopexin levels can be decreased in conditions that involve liver dysfunction, as the liver is responsible for the synthesis of haemopexin.

In the context of neuroscience, haemopexin has been studied for its potential neuroprotective effects. The brain is particularly vulnerable to damage from free heme after events such as intracerebral hemorrhage. Studies suggest that increasing haemopexin levels in the brain may help in reducing heme-induced oxidative damage and improving outcomes after hemorrhagic strokes.

Genetic Regulation

The HPX gene, which encodes haemopexin, is located on chromosome 11 in humans. The regulation of haemopexin expression is complex and involves various transcription factors that respond to changes in the body's iron status and oxidative stress levels.

See Also

• Heme oxygenase
• Hemoglobin
• Liver
• Oxidative stress