Human pyrroline‐5‐carboxylate reductase (PYCR1) acts on Δ 1 ‐piperideine‐6‐carboxylate generating L‐pipecolic acid

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.