Heme oxygenase

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heme oxygenase
Identifiers
EC number 1.14.99.3
CAS number 9059-22-7
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
Heme oxygenase
PDB 1twr EBI.jpg
crystal structures of ferrous and ferrous-no forms of verdoheme in a complex with human heme oxygenase-1: catalytic implications for heme cleavage
Identifiers
Symbol Heme_oxygenase
Pfam PF01126
Pfam clan CL0230
InterPro IPR016053
PROSITE PDOC00512
SCOP 1qq8
SUPERFAMILY 1qq8

Heme oxygenase or haem oxygenase (HO) is an enzyme that catalyzes the degradation of heme. This produces biliverdin, iron, and carbon monoxide.[1][2]

Reaction[edit]

Heme oxygenase cleaves the heme ring at the alpha-methene bridge to form either biliverdin or, if the heme is still attached to a globin, verdoglobin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase.

The reaction occurs as follows:

Heme b + 3O2 + 3½NADPH + 3½H+ → biliverdin + Fe2+ + CO + 3½NADP+ + 3H2O[3]
Heme b 
Biliverdin 

This reaction can occur in virtually every cell; the classic example is the formation of a bruise, which goes through different colors as it gradually heals: red heme to green biliverdin to yellow bilirubin. Under normal physiological conditions, the activity of heme oxygenase is highest in the spleen, where old erythrocytes are sequestrated and destroyed. In terms of molecular mechanisms, the enzyme facilitates the intramolecular hydroxylation of one meso carbon centre in the heme. [4]

Isoforms[edit]

Three isoforms of heme oxygenase are known. Heme oxygenase 1 (HO-1) is an inducible isoform in response to stress such as oxidative stress, hypoxia, heavy metals, cytokines, etc. Heme oxygenase 2 (HO-2) is a constitutive isoform that is expressed under homeostatic conditions. Both HO-1 and HO-2 are ubiquitously expressed and catalytically active.

A third heme oxygenase (HO-3) is not catalytically active, but is thought to work in oxygen sensing.

Roles in Physiology[edit]

Heme oxygenase expression is induced by oxidative stress, and in animal models increasing this expression seems to be protective. Carbon monoxide released from heme oxygenase reactions can influence vascular tone independently or influence the function of nitric oxide synthase. Carbon monoxide released from the reaction of free heme in the bloodstream of someone with the sickle-cell trait is believed to lessen the effects of cerebral Malaria.[5]

References[edit]

  1. ^ Kikuchi G, Yoshida T, Noguchi M (December 2005). "Heme oxygenase and heme degradation". Biochem. Biophys. Res. Commun. 338 (1): 558–67. doi:10.1016/j.bbrc.2005.08.020. PMID 16115609. 
  2. ^ Ryter, Stefan W.; Alam, Jawed; Choi, Augustine M. K. "Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications" Physiological Reviews (2006), 86(2), 583-650. doi:10.1152/physrev.00011.2005
  3. ^ Evans JP, Niemevz F, Buldain G, de Montellano PO (July 2008). "Isoporphyrin intermediate in heme oxygenase catalysis. Oxidation of alpha-meso-phenylheme". J. Biol. Chem. 283 (28): 19530–9. doi:10.1074/jbc.M709685200. PMC 2443647. PMID 18487208. 
  4. ^ Tadashi Yoshida, Catharina Taiko Migita "Focused Review Mechanism of heme degradation by heme oxygenase" Journal of Inorganic Biochemistry 2000, Volume 82, Issues 1–4, pages 33–41. doi:10.1016/S0162-0134(00)00156-2
  5. ^ Danielle Morse and Augustine M. K. Choi "Heme Oxygenase-1", American Journal of Respiratory and Critical Care Medicine, Vol. 172, No. 6 (2005), pp. 660-670. doi: 10.1164/rccm.200404-465SO

External links[edit]