Molecular cloning and expression of human L-pipecolate oxidase

In higher eukaryotes L-lysine can be degraded via two distinct routes inclu ding the saccharopine pathway and the L-pipecolate pathway. The saccharopin e pathway is the primary route of degradation of lysine in most tissues exc ept the brain in which the L-pipecolate pathway is most active. L-pipecolat e is formed from L-lysine via two enzymatic reactions and then undergoes de hydrogenation 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 describ ed with hyperpipecolic acidaemia. The underlying mechanism responsible for the impaired degradation of pipecolate has remained unclear through the yea rs, In order to resolve this question, we have now cloned the human L-pipec olate oxidase cDNA which codes for a protein of 390 amino acids and contain s an ADP-beta alpha beta-binding fold compatible with its identity as a fla voprotein. Furthermore, the deduced protein ends in -KAHL at its carboxy te rminus which constitutes a typical Type I peroxisomal-targeting signal (PTS I). (C) 2000 Academic Press.