Phytanic acid alpha-oxidation, new insights into an old problem: a review.
Phytanic acid (3,7,10,14-tetramethylhexadecanoic acid) is a branched-chain fatty acid which is known to accumulate in a number of different genetic diseases including Refsum disease. Due to the presence of a methyl-group at the 3-position, phytanic acid and other 3-methyl fatty acids can not undergo beta-oxidation but are first subjected to fatty acid alpha-oxidation in which the terminal carboxyl-group is released as CO(2). The mechanism of alpha-oxidation has long remained obscure but has been resolved in recent years. Furthermore, peroxisomes have been found to play an indispensable role in fatty acid alpha-oxidation, and the complete alpha-oxidation machinery is probably localized in peroxisomes. This Review describes the current state of knowledge about fatty acid alpha-oxidation in mammals with particular emphasis on the mechanism involved and the enzymology of the pathway.
Wanders
Ronald J A
RJ
Laboratory Genetic Metabolic Diseases, Department of Pediatrics/Emma Children's Hospital and Clinical Chemistry, Academic Medical Centre, University Hospital Amsterdam, Room F0-224, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. r.j.wanders@amc.uva.nl
Jansen
Gerbert A
GA
Lloyd
Matthew D
MD
D000595:Amino Acid Sequence; D000818:Animals; D002245:Carbon Dioxide / Q000737:chemistry; D019755:Carbon-Carbon Lyases / Q000737:chemistry / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D003001:Cloning, Molecular; D005561:Formates / Q000737:chemistry; D006801:Humans; D008099:Liver / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D020675:Peroxisomes / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D010831:Phytanic Acid / Q000737:chemistry* / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists; D012035:Refsum Disease / Q000378:metabolism; D014157:Transcription Factors / Q000819:agonists
D002352:Carrier Proteins; D005561:Formates; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C072087:sterol carrier proteins; C030544:formic acid; D002245:Carbon Dioxide; D010831:Phytanic Acid; D006899:Mixed Function Oxygenases; C102623:PHYH protein, human; D019755:Carbon-Carbon Lyases; C121516:2-hydroxyphytanoyl-coenzyme A lyase