Phytanic acid alpha-oxidation: accumulation of 2-hydroxyphytanic acid and absence of 2-oxophytanic acid in plasma from patients with peroxisomal disorders.
A stable isotope dilution method was developed for the measurement of 2-hydroxyphytanic acid and 2-oxophytanic acid in plasma. In plasma from healthy individuals and from patients with Refsum's disease, 2-hydroxyphytanic acid was found at levels less than 0.2 mumol/l, whereas the acid accumulated in plasma from patients with rhizomelic chondrodysplasia punctata, generalized peroxisomal dysfunction, and a single peroxisomal beta-oxidation enzyme deficiency. In plasma from both healthy controls and patients with peroxisomal disorders, 2-oxophytanic acid was undetectable. Four different groups of diseases were characterized with a defective phytanic acid alpha-oxidation and/or pristanic acid beta-oxidation: 1) Refsum's disease, with a defect at phytanic acid alpha-hydroxylation; 2) rhizomelic chondrodysplasia punctata, with a defect at 2-hydroxyphytanic acid decarboxylation; 3) generalized peroxisomal disorders, with defects at 2-hydroxyphytanic acid decarboxylation and at pristanic acid beta-oxidation; 4) single peroxisomal beta-oxidation enzyme deficiencies, with a defect at pristanic acid beta-oxidation, resulting in an impaired phytanic acid alpha-oxidation by inhibition. The results indicate that 2-hydroxyphytanic acid decarboxylation and pristanic acid beta-oxidation take place in peroxisomes.
ten Brink
H J
HJ
Department of Pediatrics, Free University Hospital, Amsterdam, The Netherlands.
Schor
D S
DS
Kok
R M
RM
Poll-The
B T
BT
Wanders
R J
RJ
Jakobs
C
C
D000293:Adolescent; D000328:Adult; D002250:Carbon Radioisotopes; D002648:Child; D002675:Child, Preschool; D005227:Fatty Acids / Q000097:blood; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D010831:Phytanic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism*; D012035:Refsum Disease / Q000097:blood* / Q000378:metabolism
D002250:Carbon Radioisotopes; D005227:Fatty Acids; D010831:Phytanic Acid; C002585:2-hydroxyphytanic acid; C056198:2-oxophytanic acid; C002844:pristanic acid