Phytanoyl-CoA dioxygenase
In enzymology, a phytanoyl-CoA dioxygenase (EC 1.14.11.18) is an enzyme that catalyzes the chemical reaction
- phytanoyl-CoA + 2-oxoglutarate + O2
2-hydroxyphytanoyl-CoA + succinate + CO2
The three substrates of this enzyme are phytanoyl-CoA, 2-oxoglutarate, and O2, whereas its three products are 2-hydroxyphytanoyl-CoA, succinate, and CO2.
This enzyme belongs to the family of oxidoreductases, which act on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O2 with 2-oxoglutarate as one donor, and incorporation of one atom of oxygen into each donor.
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.
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.[1]
Structural studies
As of late 2007, only one structure has been solved for this class of enzymes, with the PDB accession code 2A1X.[2]
References
- ^ Mihalik SJ, Morrell JC, Kim D, Sacksteder KA, Watkins PA, Gould SJ (October 1997). "Identification of PAHX, a Refsum disease gene". Nat. Genet. 17 (2): 185–9. doi:10.1038/ng1097-185. PMID 9326939.
- ^ McDonough MA, Kavanagh KL, Butler D, Searls T, Oppermann U, Schofield CJ (December 2005). "Structure of human phytanoyl-CoA 2-hydroxylase identifies molecular mechanisms of Refsum disease". J. Biol. Chem. 280 (49): 41101–10. doi:10.1074/jbc.M507528200. PMID 16186124.
External links
Further reading
- Jansen GA, Mihalik SJ, Watkins PA, Jakobs C, Moser HW, Wanders RJ (1998). "Characterization of phytanoyl-Coenzyme A hydroxylase in human liver and activity measurements in patients with peroxisomal disorders". Clin. Chim. Acta. 271 (2): 203–11. doi:10.1016/S0009-8981(97)00259-3. PMID 9565335.
- Wanders RJ; Mihalik, SJ; Watkins, PA; Moser, HW; Jakobs, C; Denis, S; Wanders, RJ (1996). "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". Biochem. Biophys. Res. Commun. 229 (1): 205–10. doi:10.1006/bbrc.1996.1781. PMID 8954107.
- OH, Stokke O, Jakobs C, Besley GT, Wraith JE, Wanders RJ (1997). "Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase gene". Nat. Genet. 17 (2): 190–3. doi:10.1038/ng1097-190. PMID 9326940.
- Mihalik SJ, Rainville AM, Watkins PA (1995). "Phytanic acid alpha-oxidation in rat liver peroxisomes. Production of alpha-hydroxyphytanoyl-CoA and formate is enhanced by dioxygenase cofactors". Eur. J. Biochem. 232 (2): 545–51. doi:10.1111/j.1432-1033.1995.545zz.x. PMID 7556205.
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| Enzymes |
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| Transporters |
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| Structure/Peroxin |
PEX1, PEX2 - PXMP3, PEX3, PEX5, PEX6, PEX7, PEX10, PEX11A, PEX11B, PEX11G, PEX12, PEX13, PEX14, PEX16, PEX19, PEX26
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| LAMP |
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see also intermediates, disorders
B strc: edmb (perx), skel (ctrs), epit, cili, mito, nucl (chro)
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