A L-glutamine derivative that is L-glutamine substituted by a 1-[(carboxymethyl)amino]-1-oxobutan-2-yl at the terminal amino nitrogen atom.
Identification
N-{(2S)-1-[(carboxymethyl)amino]-1-oxobutan-2-yl}-L-glutamine
Species
salmonella enterica
schizosaccharomyces pombe
homo sapiens
NCBI:txid9606 10.1074/jbc.M601876200
c57bl/6 mouse
Europe PubMed Central results
HPLC-MS/MS methods for the quantitative analysis of ophthalmic acid in rodent plasma and hepatic cell line culture medium.
Author: Geenen S, Michopoulos F, Kenna JG, Kolaja KL, Westerhoff HV, Wilson I.
Abstract: Ophthalmic acid (OA), an endogenous tripeptide analogue of glutathione, has been suggested as a potential biomarker for paracetamol/acetaminophen hepatotoxicity. Here HPLC-MS/MS methods have been developed for the precise, sensitive and specific detection and quantification of OA in in vitro cell culture medium and plasma. For the cell culture medium the LLOQ was found to be 1 ng/ml, with less than 1% between sample carry over at all concentrations and precision below 15% for within day and below 9% for between day analyses. For rat plasma the presence of endogenous OA resulted in the LLOQ being 25 ng/ml (defined as the lowest concentration on the calibration curve where the base peak was less than 20% of the LLOQ). For the plasma assay the percentage carry over was less than 1% for all concentrations and within and between batch precision was below 21%. The methods were linear for both sample types from the LLOQ up to 5 μg/ml. The method was successfully applied to the determination of OA in samples obtained following the chronic administration of the rat hepatotoxin methapyrilene, where plasma OA concentrations were observed to show a weak negative correlation with those of established liver injury biomarkers such as aspartate aminotransferase (AST).
Multiscale modelling approach combining a kinetic model of glutathione metabolism with PBPK models of paracetamol and the potential glutathione-depletion biomarkers ophthalmic acid and 5-oxoproline in humans and rats.
Author: Geenen S, Yates JW, Kenna JG, Bois FY, Wilson ID, Westerhoff HV.
Abstract: A key role of the antioxidant glutathione is detoxification of chemically reactive electrophilic drug metabolites within the liver. Therefore glutathione depletion can have severe toxic consequences. Ophthalmic acid and 5-oxoproline are metabolites involved in glutathione metabolism, which can be measured readily in the blood and urine and have been proposed as candidate biomarkers of hepatic glutathione content. However, currently it is unclear whether their concentrations in plasma exhibit a robust correlation with hepatic glutathione content. To explore this important question, we have developed a novel approach which combines a physiologically based pharmacokinetic (PBPK) model of metabolism and disposition of paracetamol (acetaminophen) with a previously developed mathematical systems model of hepatic glutathione homeostasis. Paracetamol is metabolised to reactive intermediates which deplete glutathione and cause toxicity when given at high doses. Our model correctly predicted that hepatic glutathione depletion following paracetamol administration resulted in elevated concentrations of 5-oxoproline and ophthalmic acid in blood and of 5-oxoproline in urine. However, we also found from the model that concentrations of both of the compounds were likely to be influenced by prolonged administration of paracetamol and by the concentrations of intracellular metabolites such as methionine. We conclude that care must be taken when extrapolating from concentrations of these biomarkers to hepatic glutathione status.
DOI: 10.1039/c3ib20245c
In vitro/in vivo screening of oxidative homeostasis and damage to DNA, protein, and lipids using UPLC/MS-MS.
Author: Carretero A, León Z, García-Cañaveras JC, Zaragoza A, Gómez-Lechón MJ, Donato MT, Lahoz A.
Abstract: Multiple analytical methods are required to comprehensively assess oxidative homeostasis and specific damage to macromolecules. Our aim was to develop a straightforward strategy for the fast assessment of global oxidative status and specific damage to DNA, proteins, and lipids. To this end, an analytical method, based on ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS/MS), was developed and validated for the quantification of 16 oxidative stress (OS) biomarkers. Some of these markers were unstable; thus, an easy sample treatment procedure, including fractionation and derivatization, was set up. The method was validated according to Food and Drug Administration (FDA) guidelines, and it provided good results in terms of intra- and inter-day precision (≤17.2 and 16 %, respectively), accuracy (relative error measurement between -16.6 and 19.8 %), and linearity (R (2) > 0.994). The approach was applied to determine the oxidative insult provoked to cultured rat hepatocytes by cumene hydroperoxide and to analyze the liver and serum samples from patients diagnosed with nonalcoholic steatohepatitis. In both studies, significant differences were found if compared to the corresponding control groups; interestingly, ophthalmic acid was shown as an OS biomarker in both models for the first time. A key advantage of the novel approach in comparison with former multi-method approaches is that now a single method is applied to assess the 16 OS biomarkers. Its comprehensive capacity to profile oxidative homeostasis and damage in both in vitro and clinical samples has been illustrated, which indicates that the proposed approach is a good choice to evaluate whether OS is involved in physiological signals, diseases, or toxic events and to what extent.
Gongylonema sp. in the Tongue of a Brown-Nosed Coati (Nasua nasua) from the Brazilian Atlantic Forest.
Author: Soares R, Bueno C, Vieira FM, Muniz-Pereira LC.
Abstract: Two parasites were collected from the epithelial layer of the tongue mucosa of a brown-nosed coati (Nasua nasua) in an area of Atlantic Forest in Minas Gerais State, Brazil. These were identified as female Gongylonema sp. nematodes, not previously reported in Brazilian wild carnivores.