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LYSINE METABOLISM IN THE RAT BRAIN: THE PIPECOLIC ACID‐FORMING PATHWAY
Author(s) -
Chang YungFeng
Publication year - 1978
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1978.tb06536.x
Subject(s) - pipecolic acid , lysine , metabolite , metabolism , biochemistry , urine , chemistry , amino acid
— Employing both the intraventricular and intraperitoneal injection techniques, 14 C‐ l ‐lysine at non‐overloading concentrations was found to be metabolized to l ‐ 14 C‐pipecolic acid at significantly high levels in the rat. Labeled pipecolic acid in the brain and liver was only found at rather low levels 24 h after intraperitoneal administration of 14 C‐ l ‐lysine regardless of non‐labeled lysine metabolite overload. A marked enhancement of pipecolic acid labeling was only found in the brain when 14 C‐ l ‐lysine was intraventricularly administered to animals under various lysine metabolite overloads. While overloading doses of non‐labeled saccharopine or α‐aminoadipate did not significantly alter the labeling patterns of pipecolic acid in the brain, liver or urine when 14 C‐ l ‐lysine was intraperitoneally administered, pipecolate overloading markedly reduced labeled pipecolic acid levels in the brain, liver and urine. These results indicate: pipecolic acid formation is subject to product inhibition, and saccharopine is not in the pathway of pipecolic acid synthesis from l ‐lysine. The labeling pattern of lysine metabolites was not significantly affected by the overloading injection of pipecolic acid when 14 C‐ l ‐lysine was intraventricularly administered suggesting a blood‐brain barrier for pipecolate. Besides 14 C‐pipecolic acid, labeled α‐aminoadipic acid was also found at significant levels mostly in the brain. Labeled saccharopine was not detected in any tissues or urine samples analyzed. The 14 C‐ l ‐lysine metabolic pattern of the newborn rats did not seem to be any different from the adult rats, i.e. labeled pipecolic acid was also detected in substantial quantities in the brain, liver and urine 5 h after injection. 14 C‐ d ‐Lysine was mainly metabolized to l ‐ 14 C‐pipecolic acid through either route of administration. These experimental evidences indicate that the pipecolic acid‐forming pathway is a significant route for lysine metabolism in the rat, and that the rat brain probably utilizes this pathway mainly for lysine metabolism. The present study also discusses the potential neurological significance of the pipecolic acid pathway in relation to the major lysine metabolic pathway (the saccharopine pathway).