Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.3.2.3 (glutathione synthetase)
 678 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The kinetics of several metabolic reactions in intact human erythrocytes and in lysates were studied using 1H spin-echo and 13C nuclear magnetic resonance spectroscopy (NMR). The reactions monitored involved the following enzymes: (1) arginase, (2) glutathione reductase, (3) glutathione synthetase, (4) gamma-glutamyl cyclotransferase, (5) di- and tripeptidase, and (6) NAD-glycohydrolase; the first six enzymes are cytosolic whilst the latter is membrane associated. Detailed kinetics of the arginase reaction are given together with the rate of arginine transport into the cells.
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PMID:Monitoring metabolic reactions in erythrocytes using NMR spectroscopy. 614 35

Myeloid-derived suppressor cells (MDSC) play an important role in tumor escape by suppressing T-cell responses. MDSC represent a group of cells of myeloid lineage at different stages of differentiation. Increased arginase activity and production of reactive oxygen species (ROS) are among the main functional characteristics of these cells. Recent studies have shown that all-trans retinoic acid (ATRA) had a potent activity in eliminating MDSC in cancer patients and in tumor-bearing mice. ATRA differentiates these cells into mature myeloid cells. However, the mechanism of this effect is unclear. Here, we have shown that ATRA dramatically and specifically up-regulated gene expression and protein level of glutathione synthase (GSS) in MDSC. This resulted in accumulation of glutathione (GSH) in these cells, observed in both mice and cancer patients. Blockade of GSH synthesis cancelled the effect of ATRA on MDSC. Accumulation of GSH in these cells using N-acetyl-L-cysteine mimicked the effect of ATRA on MDSC differentiation. Analysis of potential mechanisms of ATRA effect on GSS revealed that ATRA regulates its expression not by directly binding to the promoter but primarily via activation of extracellular signal-regulated kinase 1/2. Thus, ATRA induced differentiation of MDSC primarily via neutralization of high ROS production in these cells. This novel mechanism involves specific up-regulation of GSS and accumulation of GSH and could be used in developing and monitoring therapeutic application of ATRA.
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PMID:Mechanism of all-trans retinoic acid effect on tumor-associated myeloid-derived suppressor cells. 1800 48