Summary: Heme oxygenase
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Heme oxygenase Edit Wikipedia article
|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / EGO|
crystal structures of ferrous and ferrous-no forms of verdoheme in a complex with human heme oxygenase-1: catalytic implications for heme cleavage
Heme oxygenase or haem oxygenase (HO) is an enzyme that catalyzes the degradation of heme. This produces biliverdin, ferrous iron, and carbon monoxide. There is limited evidence that levels of heme oxygenase are positive predictors of metabolic disease, insulin resistance, and metaflammation.
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 comprises three steps, which may be:
- Heme b3+ + O
2 + NADPH + H+
→ α-meso-hydroxyheme3+ + NADP+
- α-meso-hydroxyheme3+ + H+
2 → verdoheme4+ + CO + H2O
- verdoheme4+ + 7/2 NADPH + O
2+ 3/2 H+
→ biliverdin + Fe2+ + 7/2 NADP+
- Heme b3+ + O
The sum of these reactions is:
- Heme b3+ + 3O
2 + 9/2 NADPH + 7/2 H+
→ biliverdin + Fe2+ + CO + 9/2 NADP+
If the iron is initially in the +2 state, the reaction could be:
- Heme b2+ + 3O2 + 4 NADPH + 4 H+ → biliverdin + Fe2+ + CO + 4 NADP+ + 3H2O
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.
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. HO-1 is encoded by the HMOX1 gene and HO-2 by HMOX2.
A third heme oxygenase (HO-3) is not catalytically active, but is thought to work in oxygen sensing.
Roles in physiology
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.
- 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.
- 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
- Jais, Alexander (2014). "Heme Oxygenase-1 Drives Metaflammation and Insulin Resistance in Mouse and Man". Cell. 158 (1): 25–40. doi:10.1016/j.cell.2014.04.043. PMID 24995976. Retrieved 10 May 2016.
- 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 . PMID 18487208. The reference does not give the exact stoichiometry of each reaction.
- Yoshida, Tadashi; Taiko Migita, Catharina (2000). "Focused Review Mechanism of heme degradation by heme oxygenase". Journal of Inorganic Biochemistry. 82 (1–4): 33–41. doi:10.1016/S0162-0134(00)00156-2.
- 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
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This tab holds annotation information from the InterPro database.
InterPro entry IPR016053
Haem oxygenase (EC) (HO) [PUBMED:3290025] is the microsomal enzyme that, in animals, carries out the oxidation of haem, it cleaves the haem ring at the alpha-methene bridge to form biliverdin and carbon monoxide [PUBMED:3032976]. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. In mammals there are three isozymes of haem oxygenase: HO-1 to HO-3. The first two isozymes differ in their tissue expression and their inducibility: HO-1 is highly inducible by its substrate haem and by various non-haem substances, while HO-2 is non-inducible. It has been suggested [PUBMED:8093563] that HO-2 could be implicated in the production of carbon monoxide in the brain where it is said to act as a neurotransmitter. In the genome of the chloroplast of red algae as well as in cyanobacteria, there is a haem oxygenase (gene pbsA) that is the key enzyme in the synthesis of the chromophoric part of the photosynthetic antennae [PUBMED:9326680]. A haem oxygenase is also present in the bacteria Corynebacterium diphtheriae (gene hmuO), where it is involved in the acquisition of iron from the host haem [PUBMED:9006041]. There is, in the central section of these enzymes, a well-conserved region centred on a histidine residue.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||heme oxygenase (decyclizing) activity (GO:0004392)|
|Biological process||heme oxidation (GO:0006788)|
|oxidation-reduction process (GO:0055114)|
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This clan includes the Heme oxygenase family as well as the TENA/THI-4/PQQC family that are less well characterised .
The clan contains the following 5 members:DUF3050 DUF3865 Haem_oxygenas_2 Heme_oxygenase TENA_THI-4
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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|Author:||Finn RD , Bateman A|
|Number in seed:||18|
|Number in full:||2944|
|Average length of the domain:||190.00 aa|
|Average identity of full alignment:||22 %|
|Average coverage of the sequence by the domain:||75.15 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||20|
|Download:||download the raw HMM for this family|
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There is 1 interaction for this family. More...
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Heme_oxygenase domain has been found. There are 169 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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