title: Molecular cloning and expression of human L-pipecolate oxidase.
abstract: In higher eukaryotes L-lysine can be degraded via two distinct routes including the saccharopine pathway and the L-pipecolate pathway. The saccharopine pathway is the primary route of degradation of lysine in most tissues except the brain in which the L-pipecolate pathway is most active. L-pipecolate is formed from L-lysine via two enzymatic reactions and then undergoes dehydrogenation to Delta(1)-piperideine-6-carboxylate. At least in humans and monkeys, this is brought about by the enzyme L-pipecolate oxidase (PIPOX) localized in peroxisomes. In literature, several patients have been described with hyperpipecolic acidaemia. The underlying mechanism responsible for the impaired degradation of pipecolate has remained unclear through the years. In order to resolve this question, we have now cloned the human L-pipecolate oxidase cDNA which codes for a protein of 390 amino acids and contains an ADP-betaalphabeta-binding fold compatible with its identity as a flavoprotein. Furthermore, the deduced protein ends in -KAHL at its carboxy terminus which constitutes a typical Type I peroxisomal-targeting signal (PTS I).
authors.affiliation: Department of Clinical Chemistry, Universtity of Amsterdam, Academic Medical Centre, Amsterdam, 1100 DE, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: IJlst
authors.forename: I
authors.initials: I
authors.lastname: de Kromme
authors.forename: W
authors.initials: W
authors.lastname: Oostheim
authors.forename: R J
authors.initials: RJ
authors.lastname: Wanders
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D004926:Escherichia coli; D005420:Flavoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000882:Haplorhini; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008969:Molecular Sequence Data; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D010875:Pipecolic Acids / Q000378:metabolism; D016133:Polymerase Chain Reaction; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D050879:Sarcosine Oxidase
chemical_list: D005420:Flavoproteins; D010875:Pipecolic Acids; D011994:Recombinant Proteins; D000587:Oxidoreductases Acting on CH-NH Group Donors; C494349:PIPOX protein, human; D050879:Sarcosine Oxidase; C032771:L-pipecolate dehydrogenase; C031345:pipecolic acid; D008239:Lysine