Lysine metabolism in the human and the monkey: Demonstration of pipecolic acid formation in the brain and other organs

Abstract

Metabolism of L-[U-14C]lysine was studied in the human autopsy tissues and the intact monkeys through intracerebroventricular and intravenous injections. The human tissues were more active in the metabolism of L-[14C]lysine to [14C]pipecolate than the rat tissues previously reported. This metabolism was equally active in the phosphate (pH 7) and the glycyl-glycine (pH 8.6) buffers with the brain and the kidney having higher activity than the liver. Besides [14C]pipecolate, traces of [14C]saccharopine and alpha-[14C]aminoadipate were also detected in the liver incubation. Twenty-four hr after intraventricular injection of L-[14C]lysine to the monkey, substantial labeling of pipecolate and alpha-aminoadipate was observed in the brain and spinal cord, with the kidney, liver and the plasma having much reduced levels. Radioactivity levels of these two compounds were found low in the organs and plasma of the intravenously injected monkey. The urine of both monkeys contained only traces of [14C]pipecolate, even though it contained high levels of L-[14C]lysine and alpha-[14C]aminoadipate. It was concluded that L-lysine is actively metabolized to pipecolate and alpha-aminoadipate in the human and the monkey, that this reaction is most active in the brain when L-lysine is intraventricularly administered, and that in contrast to the rat, the monkey may have an effective renal reabsorption for pipecolate which is similar to the human.

Identification of the 2-Hydroxyglutarate and Isovaleryl-CoA Dehydrogenases as Alternative Electron Donors Linking Lysine Catabolism to the Electron Transport Chain ofArabidopsisMitochondria

“…Current knowledge of mammalian Lys catabolism is largely based on a range of studies in different species in which [ 14 C]-labeled Lys was supplied as tracer (Ghadimi et al, 1971;Chang, 1982). These studies, alongside a more recent 15 N study (Struys and Jakobs, 2010), have facilitated the elucidation of the entire degradative pathway in mammals.…”

Aldehyde Dehydrogenase 7A1 (ALDH7A1) Is a Novel Enzyme Involved in Cellular Defense against Hyperosmotic Stress

“…The saccharopine pathway is the predominant pathway utilized in higher eukaryotes and is important for lysine degradation in the liver and kidney. The pipecolic acid pathway is the major route for lysine degradation in the brain (44,64,65). The ALDH7A1 tissue distribution described herein closely correlates with expected expression patterns based on regions of high lysine degradation, most notably high expression in the kidney, liver, and brain.…”

Glutamate transporters in brain ischemia: to modulate or not?

“…EAATs participate in the regulation of system x c - [122] . An α-aminoadipate (a molecule, which can be transported through system x c -and a metabolite of lysine metabolism in the brain) inhibits this system [149] . In addition, acidosis might also affect system x c -.…”