Pipecolic acid (PA) is the major metabolic intermediate of lysine in the mammalian brain. Lysine degradation may occur in mitochondria by a bifunctional enzyme complex α-aminoadipic semialdehyde synthase through its lysine-ketoglutarate reductase and saccharopine dehydrogenase activities. The transamination of amino group in α-ketoglutarate leads to the intermediate saccharopine which is converted to acetyl-CoA and enters the citric acid cycle. Lysine can also be degraded by an alternative pathway in the peroxisomes releasing PA which is subsequently oxidized to α-aminoadipic semialdehyde, joining the saccharopine pathway. Some actions in the central nervous system have been attributed to PA because it is considered a modulator that increases the release and decreases the uptake of γ-aminobutyric acid (GABA) by brain neurons.
Figure 1 Structure ensemble for pipecolic acid derivative binding to BpML1.
PA is present at high concentrations in several metabolic disorders such as Zellweger Syndrome, a genetic disorder characterized by peroxisome formation defect leading to deficiency of the activity of peroxisomal PA oxidase, enzyme responsible for PA oxidation. Increased levels of PA are also observed in hyperlysinemia, an autosomal recessive disease caused by a defect in the bifunctional protein α-aminoadipic semialdehyde synthase, and in neonatal adrenoleukodystrophy. Moreover, increased PA levels were also reported in patients with pyridoxine-dependent seizures, probably due to inhibition of α- aminoadipic acid transaminase involved in its catabolism. Patients mainly present progressive neurological symptoms with growth and mental retardation, hepatic dysfunction and hypotonia.
PA catabolic pathway produces H2O2 by reactions catalysed by oxidases. Reactive species participate in both pathological and physiological processes in the organism. In healthy aerobes, production of reactive species is approximately balanced with antioxidant defense systems. However, the excess of these compounds caused by their overproduction and/or by diminished antioxidant defenses may lead to cell injury and death, as a result of lipid, protein and DNA oxidative damage. Currently, a reliable and reproducible method using highly sensitive LC-MS/MS platform for the rapid identification and quantification of pipecolic acid in different sample types has been established by the experienced scientists at Creative Proteomics, which can satisfy the needs of academic and industrial study in your lab.
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Staffed by experienced biological scientists, Creative Proteomics can provide a wide range of services ranging from the sample preparation to the lipid extraction, characterization, identification and quantification. We are willing to provide our customer the outstanding pipecolic acid analysis service with accurate and reliable results, quick turnaround, saving you time and resources! Please feel free to contact us to discuss the wide range of services we can perform.