Abstract
The mechanism of the initial steps in lysine metabolism in vivo is unsettled, although enzymic evidence suggests that metabolism proceeds via conjugation of the ε-amino group with α-ketoglutarate forming saccharopine (SAC). An alternate pathway involves removing the α-amino group and cyclization to form pipecolic acid (PIP). Both hypotheses propose that α-aminoadipic acid (AA) is produced after these initial steps. Elucidation of this pathway is important to understand the metabolic basis of saccharopinuria and pipecolic aciduria. We administered [15N]-lysine labelled at the α or ε position to hypoglycin-treated rats and determined N enrichment of aminoacid intermediates using GC/MS. Hypoglycin inhibits glutaryl-CoA dehydrogenase, causing accumulation of glutaric acid, AA, and SAC in urine. When L-[α-15N]lysine was administered, SAC and AA were enriched 18.2 and 17.6 atom %, respectively. PIP was not enriched. Peak enrichment of blood AA occurred slightly later than peak lysine enrichment, suggesting a precursor-product relationship. L-[ε-15 N]lysine administration caused enrichment of urinary SAC comparable to that with L-[α-15N]lysine but urine and plasma AA were not enriched. Urinary PIP was 15.7 atom % enriched. With D-[ε-15N]lysine there was 80.6 atom % enrichment in urine PIP, and no enrichment of SAC or AA. These data indicate that L-lysine is mainly metabolized via SAC and AA, with a small portion metabolized to PIP, a dead end product.
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Hyman, D., Ito, T., Aberhart, J. et al. [15N]LYSINE METABOLISM IN HYPOGLYCIN-TREATED RATS: EVIDENCE FOR THE SACCHAROPINE PATHWAY AS THE MAJOR PATHWAY IN VIVO. Pediatr Res 18 (Suppl 4), 300 (1984). https://doi.org/10.1203/00006450-198404001-01245
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DOI: https://doi.org/10.1203/00006450-198404001-01245