Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.5.1.47 (cysteine synthase)
 625 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has previously been found that chronic O2 deficiency decreases activity of the enzymes of the glutathione (GSH) redox system in the liver. To study the effects of O2 deficiency on intestinal detoxication capacity, pair-fed (16 g food/day) Sprague-Dawley rats were exposed to air (20.9% O2; n = 4) or 10% O2 (n = 4) for 10 days. Animals were killed, and intestinal mucosal homogenate (20% wt/vol) was obtained and assayed for activities of glucose-6-phosphate dehydrogenase (G6PD), GSH peroxidase (GSHPx), GSH disulfide reductase (GSSGRd), and gamma-glutamyl cysteine synthetase (gamma-GCS). Hypoxia decreases activities of GSHPx, GSSGRd, and gamma-GCS by approximately 50%, which suggests compromised detoxication. A proximal-to-distal reduction in enzymatic capacity indicates impairment of detoxication may be more pronounced in the distal intestine. G6PD, a key enzyme in NADPH production, remains unchanged. Urinary malondialdehyde was also monitored. Hypoxic rats exhibited a threefold increase in thiobarbituric acid-reactive substance, consistent with a generalized oxidative stress in these animals. Taken together, the results indicate that chronic hypoxia promotes tissue oxidative stress and impairs the ability of the enterocyte to metabolize ingested oxidants.
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PMID:Chronic hypoxia and glutathione-dependent detoxication in rat small intestine. 892 4

We have employed proteomics to identify proteins upregulated in the amastigote life-stage of Leishmaniapanamensis, using axenically-differentiated forms as models of authentic intracellular parasites. Resolution of the soluble proteomes of axenic amastigotes and promastigotes by two-dimensional electrophoresis (2DE) in the neutral pI range (5-7) revealed equivalent numbers of protein spots in both life-stages (644-682 using Coomassie Blue and 851-863 by silver staining). Although representing a relatively low proportion (8.1-10.8%) of the predicted 8000 gene products of Leishmania, these proteome maps enabled the reproducible detection of 75 differentially-regulated protein spots in amastigotes, comprising 24 spots "uniquely" expressed in this life-stage and 51 over-expressed by 1.2-5.7-fold compared to promastigotes. Of the 11 amastigote-specific spots analysed by mass spectrometry (MS), 5 yielded peptide sequences with no orthologues in Leishmania major, and the remaining 6 were identified as 7 distinct proteins (some of which were truncated isoforms) representing several functional classes: carbohydrate/energy metabolism (fructose 1,6-bisphosphate aldolase, glucose 6-phosphate dehydrogenase, pyruvate dehydrogenase), stress response (heat shock protein [HSP] 83), cell membrane/cytoskeleton (beta-tubulin), amino acid metabolism (cysteine synthase) and cell-cycle (ran-binding protein). Four additional over-expressed spots were tentatively identified as HSPs 60 and 70 and HSP 70-related proteins -1 and -4 by positional analogy with these landmark proteins in the Leishmania guyanensis proteome. Our data demonstrate the feasibility of proteomics as an approach to identify novel developmentally-regulated proteins linked to Leishmania differentiation and intracellular survival, while simultaneously pinpointing therapeutic targets. In particular, the amastigote-specific expression of cysteine synthase underlines the importance of de novo cysteine synthesis both as a potential parasite virulence factor and as a major metabolic difference from mammalian host cells.
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PMID:Identification of developmentally-regulated proteins in Leishmania panamensis by proteome profiling of promastigotes and axenic amastigotes. 1653 Feb 78