title: Resolution of the phytanic acid alpha-oxidation pathway: identification of pristanal as product of the decarboxylation of 2-hydroxyphytanoyl-CoA.
abstract: The structure and enzymology of the phytanic acid alpha-oxidation pathway have long remained an enigma. Recent studies have shown that phytanic acid first undergoes activation to its coenzyme A ester, followed by hydroxylation to 2-hydroxyphytanoyl-CoA. In this paper we have studied the mechanism of decarboxylation of 2-hydroxyphytanoyl-CoA in human liver. To this end, human liver homogenates were incubated with 2-hydroxyphytanoyl-CoA in the presence or absence of NAD+. Hereafter, the medium was analyzed for the presence of pristanal and pristanic acid by gas chromatography mass spectrometry. Our results show that pristanal is formed from 2-hydroxyphytanoyl-CoA. Pristanal is subsequently oxidized to pristanic acid in a NAD+ dependent reaction. These results finally resolve the mechanism of the phytanic acid alpha-oxidation process in human liver.
authors.affiliation: Department of Clinical Chemistry, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: N M
authors.initials: NM
authors.lastname: Verhoeven
authors.forename: D S
authors.initials: DS
authors.lastname: Schor
authors.forename: H J
authors.initials: HJ
authors.lastname: ten Brink
authors.forename: R J
authors.initials: RJ
authors.lastname: Wanders
authors.forename: C
authors.initials: C
authors.lastname: Jakobs
mesh_terms: D000447:Aldehydes / Q000032:analysis*; D003065:Coenzyme A / Q000378:metabolism*; D003653:Decarboxylation; D005227:Fatty Acids / Q000032:analysis*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008830:Microbodies / Q000378:metabolism; D008956:Models, Chemical; D010084:Oxidation-Reduction; D010831:Phytanic Acid / Q000031:analogs & derivatives* / Q000378:metabolism*
chemical_list: D000447:Aldehydes; D005227:Fatty Acids; C095966:hydroxyphytanoyl-coenzyme A; C107623:pristanal; D010831:Phytanic Acid; C002844:pristanic acid; D003065:Coenzyme A