Biology:Phytanoyl-CoA dioxygenase
| phytanoyl-CoA dioxygenase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 | |||||||||
| Identifiers | |||||||||
| EC number | 1.14.11.18 | ||||||||
| CAS number | 185402-46-4 | ||||||||
| 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 / QuickGO | ||||||||
| |||||||||
| phytanoyl-CoA 2-hydroxylase | |
|---|---|
| Identifiers | |
| Symbol | PHYH |
| Alt. symbols | PAHX |
| NCBI gene | 5264 |
| HGNC | 8940 |
| OMIM | 602026 |
| RefSeq | NM_001037537 |
| UniProt | O14832 |
| Other data | |
| Locus | Chr. 10 p15.3-10p12.2 |
In enzymology, a phytanoyl-CoA dioxygenase (EC 1.14.11.18) is an enzyme that catalyzes the chemical reaction
- phytanoyl-CoA + 2-oxoglutarate + O2 [math]\displaystyle{ \rightleftharpoons }[/math] 2-hydroxyphytanoyl-CoA + succinate + CO2
The three substrates of this enzyme are phytanoyl-CoA, 2-oxoglutarate (2OG), and O2, whereas its three products are 2-hydroxyphytanoyl-CoA, succinate, and CO2.
This enzyme belongs to the family of iron(II)-dependent oxygenases, which typically incorporate one atom of dioxygen into the substrate and one atom into the succinate carboxylate group. The mechanism is complex, but is believed to involve ordered binding of 2-oxoglutarate to the iron(II) containing enzyme followed by substrate. Binding of substrate causes displacement of a water molecule from the iron(II) cofactor, leaving a vacant coordination position to which dioxygen binds. A rearrangement occurs to form a high energy iron-oxygen species (which is generally thought to be an iron(IV)=O species) that performs the actual oxidation reaction.[2][3]
Nomenclature
The systematic name of this enzyme class is phytanoyl-CoA, 2-oxoglutarate:oxygen oxidoreductase (2-hydroxylating). This enzyme is also called phytanoyl-CoA hydroxylase and phytanoyl-CoA alpha-hydroxylase.[4]
Examples
In humans, phytanoyl-CoA hydroxylase is encoded by the PHYH (aka PAHX) gene and is required for the alpha-oxidation of branched chain fatty acids (e.g. phytanic acid) in peroxisomes. PHYH deficiency results in the accumulation of large tissue stores of phytanic acid and is the major cause of Refsum disease.[5]
Related enzymes
Iron(II) and 2OG-dependent oxygenases are common in microorganisms, plants, and animals; the human genome is predicted to contain about 80 examples, and the model plant Arabidopsis thaliana likely contains more.[2] In plants and microorganisms this enzyme family is associated with a large diversity of oxidative reactions.[6]
References
- ↑ "Structure of human phytanoyl-CoA 2-hydroxylase identifies molecular mechanisms of Refsum disease". The Journal of Biological Chemistry 280 (49): 41101–10. Dec 2005. doi:10.1074/jbc.M507528200. PMID 16186124.
- ↑ 2.0 2.1 Hausinger, Robert P. (2015). "CHAPTER 1. Biochemical Diversity of 2-Oxoglutarate-Dependent Oxygenases". 2-Oxoglutarate-Dependent Oxygenases. Metallobiology. pp. 1–58. doi:10.1039/9781782621959-00001. ISBN 978-1-84973-950-4.
- ↑ "Catalytic Mechanisms of Fe(II)- and 2-Oxoglutarate-dependent Oxygenases". The Journal of Biological Chemistry 290 (34): 20702–11. Aug 2015. doi:10.1074/jbc.R115.648691. PMID 26152721.
- ↑ "PHYH phytanoyl-CoA 2-hydroxylase [ Homo sapiens (human) "]. National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/gene/5264.
- ↑ "Identification of PAHX, a Refsum disease gene". Nature Genetics 17 (2): 185–9. Oct 1997. doi:10.1038/ng1097-185. PMID 9326939.
- ↑ "Structural studies on human 2-oxoglutarate dependent oxygenases". Current Opinion in Structural Biology 20 (6): 659–72. Dec 2010. doi:10.1016/j.sbi.2010.08.006. PMID 20888218.
Further reading
- "Characterization of phytanoyl-Coenzyme A hydroxylase in human liver and activity measurements in patients with peroxisomal disorders". Clinica Chimica Acta; International Journal of Clinical Chemistry 271 (2): 203–11. Mar 1998. doi:10.1016/S0009-8981(97)00259-3. PMID 9565335.
- "Phytanoyl-CoA hydroxylase is present in human liver, located in peroxisomes, and deficient in Zellweger syndrome: direct, unequivocal evidence for the new, revised pathway of phytanic acid alpha-oxidation in humans". Biochemical and Biophysical Research Communications 229 (1): 205–10. Dec 1996. doi:10.1006/bbrc.1996.1781. PMID 8954107.
- "Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase gene". Nature Genetics 17 (2): 190–3. Oct 1997. doi:10.1038/ng1097-190. PMID 9326940.
- "Phytanic acid alpha-oxidation in rat liver peroxisomes. Production of alpha-hydroxyphytanoyl-CoA and formate is enhanced by dioxygenase cofactors". European Journal of Biochemistry 232 (2): 545–51. Sep 1995. doi:10.1111/j.1432-1033.1995.545zz.x. PMID 7556205.
External links
 |  |
