Reactome: A Curated Pathway Database

Scavenging of heme from plasma (R-HSA-2168880)

Species Homo sapiens


Free heme is damaging to tissues as it intercalates into biologic membranes, perturbing lipid bilayers and promoting the conversion of low-density lipoprotein to cytotoxic oxidized products. Moreover, it represents a source of redox-active iron that, participating in the Fenton reaction, generates oxygen radicals (reviewed in Gutteridge 1989). Free heme in plasma is mainly generated from hemoglobin released by circulating erythrocytes in pathologic conditions associated with intravascular hemolysis. Free hemoglobin in plasma is scavenged by the extracellular protein haptoglobin. Haptoglobin is produced by the liver and secreted into the plasma. Haptoglobin binds dimers of hemoglobin subunits rather than the intact tetramer (reviewed in Nielsen et al. 2010, Levy et al. 2010, Ascenzi et al. 2005, Madsen et al. 2001). The resulting haptoglobin:hemoglobin complex is then bound by CD163, expressed on plasma membranes of monocytes and macrophages, and endocytosed. When the buffering capacity of plasma haptoglobin is overwhelmed, heme is released from methemoglobin and it is bound by albumin and then transferred to hemopexin (reviewed in Chiabrando et al. 2011, Nielsen et al. 2010, Tolosano et al. 2010, Ascenzi et al. 2005, Tolosano and Altruda 2002). Hemopexin is produced mainly in the liver. Once secreted into the plasma, hemopexin binds heme and the hemopexin:heme complex is then preferentially delivered to liver hepatocytes, bound by LRP1 (CD91) and endocytosed.

Locations in the PathwayBrowser
Additional Information
Compartment extracellular region , endocytic vesicle membrane , plasma membrane
Literature References
pubMedId Title Journal Year
19659436 Hemoglobin and heme scavenger receptors Antioxid. Redox Signal. 2010
19650691 Heme scavenging and the other facets of hemopexin Antioxid. Redox Signal. 2010
12042069 Hemopexin: structure, function, and regulation DNA Cell Biol. 2002
2485589 Iron and oxygen: a biologically damaging mixture Acta Paediatr Scand Suppl 1989
19659435 Haptoglobin: basic and clinical aspects Antioxid. Redox Signal. 2010
16511968 Hemoglobin and heme scavenging IUBMB Life 2005
11865982 Haptoglobin and CD163: captor and receptor gating hemoglobin to macrophage lysosomes Redox Rep. 2001
Acute Phase Proteins 2011