Phytanic acid alpha-oxidation and complementation analysis of classical Refsum and peroxisomal disorders.
We have measured the production of 14CO2 from exogenous [1-14C] phytanic acid in fibroblast monolayers from patients with classical Refsum's disease and peroxisomal disorders. Activities in the different disorders were (percentage of control): classical Refsum's disease (5%), isolated peroxisomal acyl-CoA oxidase deficiency (75%), Zellweger syndrome (4%), neonatal adrenoleukodystrophy (5%), and rhizomelic chondrodysplasia punctate (3%). Absence of complementation was demonstrated between Zellweger syndrome and infantile Refsum's disease lines after polyethylene glycol fusion, with decreases of average activity of 11% relative to unfused cell mixtures. Classical Refsum's disease, rhizomelic chondrodysplasia punctata, and neonatal adrenoleukodystrophy lines all complemented one another, and Zellweger syndrome or infantile Refsum's disease lines, with average activity increases of 522%-772%. No intragenic complementation was observed within either group. Four complementation groups were detected suggesting that at least four genes are involved in phytanic acid alpha-oxidation: one gene for the enzyme phytanic acid alpha-hydroxylase (probably mitochondrial); one gene for a regulatory factor for the expression of phytanic acid alpha-decarboxylation activity and two membrane-bound peroxisomal enzymes involved in the synthesis of plasmalogens; two genes for the assembly of functional peroxisomes and/or import of proteins into peroxisomes.
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BT
Clinique et Unité de Recherche de Génétique Médicale, INSERM U. 12, Hôpital des Enfants Malades, Paris, France.
Skjeldal
O H
OH
Stokke
O
O
Poulos
A
A
Demaugre
F
F
Saudubray
J M
JM
D000326:Adrenoleukodystrophy / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002806:Chondrodysplasia Punctata / Q000235:genetics / Q000378:metabolism; D004537:Eicosanoic Acids / Q000378:metabolism*; D005347:Fibroblasts; D005816:Genetic Complementation Test; D006801:Humans; D008830:Microbodies / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D010831:Phytanic Acid / Q000378:metabolism*; D012035:Refsum Disease / Q000235:genetics* / Q000378:metabolism; D015211:Zellweger Syndrome / Q000235:genetics / Q000378:metabolism
D004537:Eicosanoic Acids; D010831:Phytanic Acid