title: Human pyrroline-5-carboxylate reductase (PYCR1) acts on Δ(1)-piperideine-6-carboxylate generating L-pipecolic acid.
abstract: We have conducted biochemical studies with commercial available pyrroline-5-carboxylate (P5C) reductase (PYCR1) to investigate whether this enzyme plays a role in L-lysine degradation. Our recent studies with antiquitin/ALDH7A1 deficient fibroblasts revealed an alternative genesis of L-pipecolic acid, and we then hypothesized that PYCR1 was responsible for the conversion of Δ(1)-piperideine-6-carboxylate (P6C) into pipecolic acid. We here present evidence that PYCR1 is indeed able to produce L-pipecolic acid from P6C preparations, and the observed K m for this conversion is of the same magnitude as the K m described for the conversion of P5C to L-proline by PYCR1. Urine samples from antiquitin deficient individuals, who accumulate P6C, were also incubated with PYCR1 which resulted in a marked decrease of P6C and a huge increase of L-pipecolic acid as measured by LC-MS/MS, confirming that indeed PYCR1 generates L-pipecolic acid from P6C.
authors.affiliation: Metabolic Unit, Clinical Chemistry, VUmc Medical Center, The Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands, e.struys@vumc.nl.
authors.forename: Eduard A
authors.initials: EA
authors.lastname: Struys
authors.forename: Erwin E W
authors.initials: EE
authors.lastname: Jansen
authors.forename: Gajja S
authors.initials: GS
authors.lastname: Salomons
mesh_terms: D006801:Humans; D010848:Picolinic Acids / Q000378:metabolism*; D010875:Pipecolic Acids / Q000378:metabolism*; D011762:Pyrroline Carboxylate Reductases / Q000502:physiology*; D000097502:delta-1-Pyrroline-5-Carboxylate Reductase
chemical_list: D010848:Picolinic Acids; D010875:Pipecolic Acids; D011762:Pyrroline Carboxylate Reductases; D000097502:delta-1-Pyrroline-5-Carboxylate Reductase; C008919:delta-1-piperidine-6-carboxylic acid; C031345:pipecolic acid