Disease relevance of CPD-206

• Human phytanoyl-CoA hydroxylase: resolution of the gene structure and the molecular basis of Refsum's disease [1].

High impact information on CPD-206

• These results corresponded to high-affinity binding of phytanoyl-CoA to the recombinant rat SCP2 protein, as well as high 3-ketopristanoyl-CoA thiolase activity of the recombinant rat SCPx protein [2].
• Further characterization supported that the gene disruption led to inefficient import of phytanoyl-CoA into peroxisomes and to defective thiolytic cleavage of 3-ketopristanoyl-CoA [2].
• The H175A and D177A mutants did not catalyse hydroxylation of phytanoyl-CoA, consistent with their assigned role as iron(II) binding ligands [3].
• Although pristanic and phytanic acids were rapidly converted to pristanoyl-CoA and phytanoyl-CoA, respectively, they were not converted to carnitine esters by mitochondrial outer membranes [4].
• Phytanoyl-CoA is efficiently 2-hydroxylated by PAHX in vitro in the presence of mature SCP-2 [5].

Chemical compound and disease context of CPD-206

• Restoration of phytanic acid oxidation in Refsum disease fibroblasts from patients with mutations in the phytanoyl-CoA hydroxylase gene [6].

Biological context of CPD-206

• The kinetics of heat inactivation of phytanoyl-CoA ligase (in the presence of unlabeled palmitate) and palmitoyl-CoA ligase yielded a T1/2 of 3-5 min for the former and 25-35 min for the latter suggesting that phytanoyl-CoA ligase may be different from long chain acyl-CoA ligase [7].

Anatomical context of CPD-206

• The phytanoyl-CoA ligase, the first enzyme in the alpha-oxidation pathway, had activity similar to that in peroxisomes from control (9.86 +/- 0.09 nmol/h per mg protein) and Refsum (10.25 +/- 0.31 nmol/h per mg protein) fibroblasts [8].
• In one cell line, HepG2, no induction of phytanoyl-CoA hydroxylase activity was observed [9].
• After addition of phytanic acid to COS-1 cells, an increase in phytanoyl-CoA hydroxylase activity was observed within 2 h, indicating a quick cell response [9].
• This was further supported by the fact that activation of phytanic acid to phytanoyl-CoA was required only in intact mitochondria but not in mitochondria permealized with digitonin [10].

Associations of CPD-206 with other chemical compounds

• Phytanic acid oxidation: topographical localization of phytanoyl-CoA ligase and transport of phytanic acid into human peroxisomes [11].
• In conclusion, we report the unexpected requirement for ATP or GTP and Mg(2+) of phytanoyl-CoA hydroxylase in addition to the known hydroxylation cofactors [12].
• 5,8,11,14-Eicosatetraynoic acid (ETYA), an inhibitor of long-chain acyl-CoA synthetase activity, blocked phytanoyl-CoA synthesis as well as 3H-release from [2,3-3H]phytanic acid in a dose-dependent manner [13].

Gene context of CPD-206

• Phytanoyl-CoA hydroxylase (PhyH) catalyzes the conversion of phytanoyl-CoA to 2-hydroxyphytanoyl-CoA, which is the first step in the phytanic acid alpha-oxidation pathway [14].
• Phytanoyl-CoA was synthesised and used to develop in vitro assays for PAHX [15].
• Attempts to separate LCS from phytanoyl-CoA synthetase by chromatography on several matrices were unsuccessful [16].
• In conclusion, our results show that human TER is responsible for the reduction of phytenoyl-CoA to phytanoyl-CoA in peroxisomes [17].

Analytical, diagnostic and therapeutic context of CPD-206

• Preparative isoelectric focusing revealed that phytanoyl-CoA synthetase and LCS had indistinguishable isoelectric points [16].

References