Abstract
The Kynurenine (KYN) pathway of the tryptophan (TRP) metabolism comprises several highly important key interfaces in the functional interplay between immune system, endocrine system and neurotransmitter system. The first step in this pathway is mediated by two enzymes: TDO and IDO; the activity of TDO is regulated by glucocorticoids, while distinct cytokines are inducers or inhibitors of IDO. T cell tolerance is under control of IDO and the activity of several cells of both, the innate and the adaptive immune system is regulated by the KYN metabolism. On the other hand, several KYN-pathway intermediates are neuroactive, e.g. kynurenic acid (KYNA) is the only known endogenous antagonist at the NMDAR and additionally acts on the α7 nicotinic receptor, while quinolinic acid (QUIN) is an NMDAR agonist and plays a crucial role in the pathophysiology of Alzheimer’s disease. However, further progress in the field is limited by the lack of a sensitive and specific method for simultaneous determination of the complete TRP-metabolism. Therefore, we developed a method for the simultaneous detection of tryptophan and twelve metabolites in serum, cerebrospinal fluid, tissue homogenate, or cell culture supernatant. The sample preparation is a very cost-effective double-stage protein precipitation. Compared to other methods a very small amount of sample is required, as the sensitive LC–MS/MS technique is used. To increase sensitivity, the metabolites with extremely low concentration undergo an additional derivatisation process. The following analytes are detectable: TRP, 5-HTP, 5-HT, 5-HIAA, KYN, KYNA, 3-HK, 3-HAA, Anthranillic acid, Xanthurenic acid, Quinaldic acid, QUIN and Picolinic acid.
Published Version
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