Reactome | Scavenging of heme from plasma

Scavenging of heme from plasma

Stable Identifier

R-HSA-2168880

DOI

10.3180/REACT_160163.1

Type

Pathway

Species

Homo sapiens

Compartment

extracellular region, endocytic vesicle membrane, plasma membrane

ReviewStatus

5/5

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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.

Literature References

PubMed ID	Title	Journal	Year
11865982	Haptoglobin and CD163: captor and receptor gating hemoglobin to macrophage lysosomes Madsen, M, Graversen, JH, Moestrup, SK	Redox Rep.	2001
	Acute Phase Proteins Veas, F		2011
12042069	Hemopexin: structure, function, and regulation Tolosano, E, Altruda, F	DNA Cell Biol.	2002
19650691	Heme scavenging and the other facets of hemopexin Tolosano, E, Fagoonee, S, Morello, N, Vinchi, F, Fiorito, V	Antioxid. Redox Signal.	2010
19659436	Hemoglobin and heme scavenger receptors Nielsen, MJ, Møller, HJ, Moestrup, SK	Antioxid. Redox Signal.	2010
2485589	Iron and oxygen: a biologically damaging mixture Gutteridge, JM	Acta Paediatr Scand Suppl	1989
19659435	Haptoglobin: basic and clinical aspects Levy, AP, Asleh, R, Blum, S, Levy, NS, Miller-Lotan, R, Kalet-Litman, S, Anbinder, Y, Lache, O, Nakhoul, FM, Asaf, R, Farbstein, D, Pollak, M, Soloveichik, YZ, Strauss, M, Alshiek, J, Livshits, A, Schwartz, A, Awad, H, Jad, K, Goldenstein, H	Antioxid. Redox Signal.	2010
16511968	Hemoglobin and heme scavenging Ascenzi, P, Bocedi, A, Visca, P, Altruda, F, Tolosano, E, Beringhelli, T, Fasano, M	IUBMB Life	2005