Phytanic acid alpha-oxidation: identification of 2-hydroxyphytanoyl-CoA lyase in rat liver and its localisation in peroxisomes.
Phytanic acid is broken down by alpha-oxidation in three steps finally yielding pristanic acid. The first step occurs in peroxisomes and is catalysed by phytanoyl-CoA hydroxylase. We have studied the second step in the alpha-oxidation pathway, which involves conversion of 2-hydroxyphytanoyl-CoA to pristanal catalysed by 2-hydroxyphytanoyl-CoA lyase. To this end, we have developed a stable isotope dilution gas chromatography-mass spectrometry assay allowing activity measurements in rat liver homogenates. Cell fractionation studies demonstrate that in rat liver 2-hydroxyphytanoyl-CoA lyase is localised in peroxisomes. This finding may have important implications for inherited diseases in man characterised by impaired phytanic acid alpha-oxidation.
Jansen
G A
GA
University of Amsterdam, Academic Medical Centre, Department of Pediatrics, Emma Children's Hospital, Laboratory for Genetic Metabolic Diseases (Room F0-224), P.O. Box 22700, 1100 DE, Amsterdam, Netherlands.
Verhoeven
N M
NM
Denis
S
S
Romeijn
G
G
Jakobs
C
C
ten Brink
H J
HJ
Wanders
R J
RJ
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D019755:Carbon-Carbon Lyases / Q000378:metabolism*; D002458:Cell Fractionation; D005227:Fatty Acids / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D008099:Liver / Q000201:enzymology*; D008297:Male; D010084:Oxidation-Reduction; D020675:Peroxisomes / Q000201:enzymology*; D010831:Phytanic Acid / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000447:Aldehydes; D005227:Fatty Acids; C107623:pristanal; D010831:Phytanic Acid; D019755:Carbon-Carbon Lyases; C121516:2-hydroxyphytanoyl-coenzyme A lyase