Hemopexin

Hemopexin, or HPX, is a secreted plasma glycoprotein that binds free heme with very high affinity and serves as the primary heme scavenger in circulation. It is produced mainly by hepatocytes in the liver and circulates in the bloodstream as part of the body's mechanism to limit heme-induced toxicity.

Function and mechanism

During intravascular hemolysis, free heme is released and can promote oxidative damage and inflammation. Hemopexin binds heme to form a 1:1 HPX–heme complex with sub-nanomolar affinity, effectively sequestering heme in plasma. The complex is recognized and internalized by hepatocytes via receptors such as CD91/LRP1. Within the cell, heme is degraded by heme oxygenase-1 to biliverdin, iron, and carbon monoxide, with iron recycled for new heme synthesis or storage.

Clinical significance

Hemopexin helps limit heme-mediated cytotoxicity during hemolysis and inflammatory states. Plasma HPX levels decline when heme load is high because HPX is consumed by complex formation; severe or prolonged hemolysis can lead to reduced HPX availability. Congenital HPX deficiency is rare but possible. In clinical and research contexts, HPX levels can reflect intravascular hemolysis and heme burden, and experimental approaches have explored HPX administration as a therapeutic strategy to mitigate heme toxicity.

Structure and genetics

Hemopexin is a single-chain glycoprotein of roughly 60 to 65 kDa in its mature plasma form. The HPX gene encodes the protein. Through its high affinity for heme, HPX contributes to iron homeostasis and the systemic response to hemolysis by facilitating safe clearance and reuse of heme-derived iron.