Concurrent Quantification of Quinolinic, Picolinic, and Nicotinic Acids Using Electron-Capture Negative-Ion Gas Chromatography–Mass Spectrometry

Smythe, George A.; Braga, Olgar; Brew, Bruce J.; Grant, Ross; Guillemin, Gilles J.; Kerr, Stephen J.; Walker, David

doi:10.1006/abio.2001.5490

Cited by 91 publications

(74 citation statements)

References 24 publications

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“…Previous studies have demonstrated that plasma QA concentrations are eight times higher in the fetus than in the MP in sheep (Smythe et al 2002). In our study, plasma l-Kyn and QA concentrations were similar between mothers and fetuses at E20.…”

Section: Trp Metabolism In Normal Gestationsupporting

confidence: 63%

Maternal and fetal tryptophan metabolism in gestating rats: effects of intrauterine growth restriction

et al. 2015

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L-Tryptophan (L-Trp) is a precursor for serotonin (5-HT) and nicotinamide adenine dinucleotide (NAD) synthesis. Both 5-HT and NAD may impact energy metabolism during gestation given that recent studies have demonstrated that increased 5-HT production is crucial for increasing maternal insulin secretion, and that sirtuin, an NAD(+)-dependent protein deacetylase, regulates endocrine signaling. Infants born with intrauterine growth restriction (IUGR) are at a higher risk of metabolic disease once they reach adulthood. IUGR is associated with altered maternal-fetal amino acid transfer. Whether IUGR affects L-Trp metabolism in mother and fetus has not been fully elucidated. Recently, we developed an analytical method using stable isotope-labeled L-Trp to explore the metabolism of L-Trp and its main metabolites, L-kynurenine (L-Kyn), 5-HT and quinolinic acid (QA). In this study, dams submitted to dietary protein restriction throughout gestation received intravenous infusions of stable isotope-labeled (15)N2-L-Trp to determine whether L-Trp metabolism is affected by IUGR. Samples were obtained from maternal, fetal and umbilical vein plasma, as well as the amniotic fluid (AF), placenta and liver of the mother and the fetus after isotope infusion. We observed evidence for active L-Trp transfer from mother to fetus, as well as de novo synthesis of 5-HT in the fetus. Plasma 5-HT was decreased in undernourished mothers. In IUGR fetuses, maternal-fetal L-Trp transfer remained unaffected, but conversion to QA was impaired, implying that NAD production also decreased. Whether such alterations in tryptophan metabolism during gestation have adverse consequences and contribute to the increased risk of metabolic disease in IUGR remains to be explored.

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Section: Trp Metabolism In Normal Gestationsupporting

confidence: 63%

Maternal and fetal tryptophan metabolism in gestating rats: effects of intrauterine growth restriction

et al. 2015

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“…QUIN and PIC samples were analyzed by gas chromatography-mass spectrometry (GC-MS) with the spectrometer operating in electron capture negative ionization mode. Selected ions (m/z 273 for PIC and m/z 277 for d4-PIC) were then monitored (Smythe et al, 2002). The limits of quantification were Ͻ1 fmol (injected onto the column) at signal-to-noise ratios of Ͼ10:1.…”

Section: Methodsmentioning

confidence: 99%

Characterization of the Kynurenine Pathway in Human Neurons

et al. 2007

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The kynurenine pathway is a major route of L-tryptophan catabolism producing neuroactive metabolites implicated in neurodegeneration and immune tolerance. We characterized the kynurenine pathway in human neurons and the human SK-N-SH neuroblastoma cell line and found that the kynurenine pathway enzymes were variably expressed. Picolinic carboxylase was expressed only in primary and some adult neurons but not in SK-N-SH cells. Because of this difference, SK-N-SH cells were able to produce the excitotoxin quinolinic acid, whereas human neurons produced the neuroprotectant picolinic acid. The net result of kynurenine pathway induction in human neurons is therefore predicted to result in neuroprotection, immune regulation, and tumor inhibition, whereas in SK-N-SH cells, it may result in neurotoxicity, immune tolerance, and tumor promotion. This study represents the first comprehensive characterization of the kynurenine pathway in neurons and the first description of the involvement of the kynurenine pathway as a mechanism for controlling both tumor cell neurotoxicity and persistence.

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“…Gas chromatography mass spectrometry PIC and quinolinic acid (QUIN) in CSF samples were determined using gas chromatography mass spectrometry (GC-MS) in electroncapture negative ionization mode by a method previously described (Smythe et al 2002). Briefly, 50-100 lL samples of CSF were combined with 20 lL of the internal standards deuterium labelled- Fig.…”

Section: Csf Samplesmentioning

confidence: 99%

Central kynurenine pathway shift with age in women

Bie

Guest

Guillemin

et al. 2016

Journal of Neurochemistry

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Age is considered a dominant risk factor in the development of most neurodegenerative disorders. The kynurenine pathway, a major metabolic pathway of tryptophan is altered in the majority of neurodegenerative disorders. In this study, we have analysed CSF samples from 49 healthy women across a wide age range (0-90) for kynurenine pathway metabolites and the inflammatory marker neopterin. Our results show central tryptophan metabolism is increased with age in women, with an apparent shift towards the neurotoxin quinolinic acid. We also observed an increase in central levels of the inflammatory marker neopterin with age and a positive correlation between neopterin and kynurenine pathway activation. We conclude that, the changes that occur in the kynurenine pathway as a result of normal ageing are mechanistically linked to increased inflammatory signalling and have some explanatory potential with regard to ageassociated degenerative diseases in the CNS. Management of health in ageing and (preventative) treatment would do well to look to the kynurenine pathway for potentially novel solutions.

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Concurrent Quantification of Quinolinic, Picolinic, and Nicotinic Acids Using Electron-Capture Negative-Ion Gas Chromatography–Mass Spectrometry

Cited by 91 publications

References 24 publications

Maternal and fetal tryptophan metabolism in gestating rats: effects of intrauterine growth restriction

Maternal and fetal tryptophan metabolism in gestating rats: effects of intrauterine growth restriction

Characterization of the Kynurenine Pathway in Human Neurons

Central kynurenine pathway shift with age in women

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