Application | Comment | Organism |
---|---|---|
diagnostics | assays for Refsums disease should not be based on PAHX activity alone. At least four different types of mutation cause loss of PAHX activity in vivo. Mutations to the peroxisomal targeting sequence do not affect catalytic function but probably affect targeting or degradation of the enzyme. A second group of mutations, including truncation and missense mutations, results in total loss of activity. A third group of mutations results in uncoupling of substrate oxidation from that of 2-oxoglutarate. A fourth group of mutations causes partial inactivation by hindering binding/utilization of the 2-oxoglutarate cosubstrate and/or iron(II) cofactor. From the therapeutic and biochemical view-point the latter two groups are particularly interesting since it may be possible to restore their activity with modified cosubstrates | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
wild-type and mutant enzymes, expression in Escherichia coli | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
D177A | mutant enzyme does not catalyze hydroxylation of phytanoyl-CoA | Homo sapiens |
G204S | mutation causes partial uncoupling of 2-oxoglutarate conversion from phytanoyl-CoA oxidation | Homo sapiens |
H175A | mutant enzyme does not catalyze hydroxylation of phytanoyl-CoA | Homo sapiens |
N269H | mutation causes partial uncoupling of 2-oxoglutarate conversion from phytanoyl-CoA oxidation | Homo sapiens |
P29S | clinically observed mutant is fully active, mutation may result in a defective targeting of the protein to peroxisomes | Homo sapiens |
Q176K | mutation causes partial uncoupling of 2-oxoglutarate conversion from phytanoyl-CoA oxidation | Homo sapiens |
R275Q | mutation results in impaired 2-oxoglutarate binding | Homo sapiens |
R275W | mutation results in impaired 2-oxoglutarate binding | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
peroxisome | - |
Homo sapiens | 5777 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Iron | required | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
phytanoyl-CoA + 2-oxoglutarate + O2 | Homo sapiens | Refsums disease ia a neurological syndrome characterized by adult-onset retinitis pigmentosa, anosemia, sensory neuropathy and phytanic acidaemia. Many cases are caused by mutations in peroxidomal oxygenase phytanoyl-CoA 2-hydroxylase | 2-hydroxyphytanoyl-CoA + succinate + CO2 | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | O14832 | - |
- |
Purification (Comment) | Organism |
---|---|
- |
Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
liver | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
phytanoyl-CoA + 2-oxoglutarate + O2 | Refsums disease ia a neurological syndrome characterized by adult-onset retinitis pigmentosa, anosemia, sensory neuropathy and phytanic acidaemia. Many cases are caused by mutations in peroxidomal oxygenase phytanoyl-CoA 2-hydroxylase | Homo sapiens | 2-hydroxyphytanoyl-CoA + succinate + CO2 | - |
? |