Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
FEBS Lett. 2010 Jan 4;584(1):181-6. doi: 10.1016/j.febslet.2009.11.055.
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.
哺乳动物赖氨酸的降解途径被认为有两条，即：赖氨酰琥珀酸途径和哌可酸途径，这两条途径最终在α-氨基己二酸半醛（α-AASA）水平上汇聚。α-AASA 脱氢酶缺陷型成纤维细胞在添加 L-[α-(15)N]赖氨酸或 L-[ε-(15)N]赖氨酸的细胞培养基中培养，以探讨赖氨酸降解的确切途径。L-[α-(15)N]赖氨酸被代谢为[(15)N]赖氨酰琥珀酸、[(15)N]α-AASA、[(15)N]Δ(1)-哌啶酸-6-羧酸酯，以及令人惊讶的[(15)N]哌可酸，而 L-[ε-(15)N]赖氨酸仅形成[(15)N]赖氨酰琥珀酸。这些结果表明，赖氨酸在成纤维细胞中仅通过赖氨酰琥珀酸途径降解，而哌可酸则来自替代前体。我们假设哌可酸来自 Δ(1)-哌啶酸-6-羧酸酯，通过 Δ(1)-吡咯啉-5-羧酸还原酶的作用，该酶参与脯氨酸代谢。
