title: Metabolism of lysine in alpha-aminoadipic semialdehyde dehydrogenase-deficient fibroblasts: evidence for an alternative pathway of pipecolic acid formation.
abstract: The mammalian degradation of lysine is believed to proceed via two distinct routes, the saccharopine and the pipecolic acid routes, that ultimately converge at the level of alpha-aminoadipic semialdehyde (alpha-AASA). alpha-AASA dehydrogenase-deficient fibroblasts were grown in cell culture medium supplemented with either L-[alpha-(15)N]lysine or L-[epsilon-(15)N]lysine to explore the exact route of lysine degradation. L-[alpha-(15)N]lysine was catabolised into [(15)N]saccharopine, [(15)N]alpha-AASA, [(15)N]Delta(1)-piperideine-6-carboxylate, and surprisingly in [(15)N]pipecolic acid, whereas L-[epsilon-(15)N]lysine resulted only in the formation of [(15)N]saccharopine. These results imply that lysine is exclusively degraded in fibroblasts via the saccharopine branch, and pipecolic acid originates from an alternative precursor. We hypothesize that pipecolic acid derives from Delta(1)-piperideine-6-carboxylate by the action of Delta(1)-pyrroline-5-carboxylic acid reductase, an enzyme involved in proline metabolism.
authors.affiliation: Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands. e.struys@vumc.nl
authors.forename: Eduard A
authors.initials: EA
authors.lastname: Struys
authors.forename: Cornelis
authors.initials: C
authors.lastname: Jakobs
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000172:deficiency*; D002460:Cell Line; D005347:Fibroblasts / Q000201:enzymology*; D006801:Humans; D050647:L-Aminoadipate-Semialdehyde Dehydrogenase; D008239:Lysine / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000172:deficiency*; D010848:Picolinic Acids / Q000378:metabolism; D010875:Pipecolic Acids / Q000378:metabolism*; D011758:Pyrroles / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D010848:Picolinic Acids; D010875:Pipecolic Acids; D011758:Pyrroles; C015485:delta-1-pyrroline-5-carboxylate; C008919:delta-1-piperidine-6-carboxylic acid; D000444:Aldehyde Dehydrogenase; C503677:AASDH protein, human; D050647:L-Aminoadipate-Semialdehyde Dehydrogenase; C031345:pipecolic acid; D008239:Lysine