[HTML][HTML] Metabolism of lysine in α-aminoadipic semialdehyde dehydrogenase-deficient fibroblasts: Evidence for an alternative pathway of pipecolic acid formation
EA Struys, C Jakobs - FEBS letters, 2010 - Elsevier
EA Struys, C Jakobs
FEBS letters, 2010•ElsevierThe 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 α-
aminoadipic semialdehyde (α-AASA). α-AASA dehydrogenase-deficient fibroblasts were
grown in cell culture medium supplemented with either l-[α-15N] lysine or l-[ε-15N] lysine to
explore the exact route of lysine degradation. l-[α-15N] lysine was catabolised into [15N]
saccharopine,[15N] α-AASA,[15N] Δ1-piperdeine-6-carboxylate,[15N] α-AAA, and …
saccharopine and the pipecolic acid routes, that ultimately converge at the level of α-
aminoadipic semialdehyde (α-AASA). α-AASA dehydrogenase-deficient fibroblasts were
grown in cell culture medium supplemented with either l-[α-15N] lysine or l-[ε-15N] lysine to
explore the exact route of lysine degradation. l-[α-15N] lysine was catabolised into [15N]
saccharopine,[15N] α-AASA,[15N] Δ1-piperdeine-6-carboxylate,[15N] α-AAA, and …
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 α-aminoadipic semialdehyde (α-AASA). α-AASA dehydrogenase-deficient fibroblasts were grown in cell culture medium supplemented with either l-[α-15N]lysine or l-[ε-15N]lysine to explore the exact route of lysine degradation. l-[α-15N]lysine was catabolised into [15N]saccharopine, [15N]α-AASA, [15N]Δ1-piperdeine-6-carboxylate, [15N]α-AAA, and surprisingly in [15N]pipecolic acid, whereas l-[ε-15N]lysine resulted only in the formation of [15N]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 Δ1-piperdeine-6-carboxylate by the action of Δ1-pyrroline-5-carboxylic acid reductase, an enzyme involved in proline metabolism.
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