Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.5.1.47 (cysteine synthase)
625 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inhibition of Salmonella typhimurium by 1,2,4-triazole appears to be mediated through an effect on L-cysteine biosynthesis. O-Acetylserine sulfhydrylase A, the final enzyme in the L-cysteine biosynthetic pathway, was found to catalyze a reaction (triazolylase) between O-acetyl-L-serine and 1,2,4-triazole, giving 1,2,4-triazole-1-alanine as a product. In wild type S. typhimurium grown on 4 mM 1,2,4-triazole, 97% of the total O-acetyl-L-serine synthesized in vivo is incorporated into 1,2,4-triazole-1-alanine. 1,2,4-triazole also significantly lowers the levels of several of the enzymes necessary for sulfate reduction. This effect is presumably due to the ability of the inhibitor to lower intracellular concentrations of O-acetyl-L-serine, an inducer of these enzymes. Inhibition of growth is probably caused by L-cysteine starvation, arising from the decreased availability of the L-cysteine precursors, sulfide and O-acetyl-L-serine. Two 1,2,4-triazole-resistant strains bearing mutations in cysK, the structural gene for O-acetylserine sulfhydrylase A, incorporate only small quantities of O-acetyl-L-serine into 1,2,4-triazole-1-alanine in vivo. In vitro studies, using purified preparations of O-acetylserine sulfhydrylase A, revealed greater losses of triazolylase activity than sulfhydrylase activity in the enzymes from both cysK mutants. Resistance to 1,2,4-triazole apparently can arise from mutations leading to a preferential loss of triazolylase activity or from mutations which diminish both activities to the extent that high concentrations of O-acetyl-L-serine and sulfide accumulate behind the sulfhydrylase reaction.
...
PMID:Studies on the mechanism of inhibition of Salmonella typhimurium by 1,2,4-triazole. 110 Jun 24

The existence of two postulated pathways of anabolic cysteine biosynthesis in Aspergillus midulans was investigated. No activities of the postulated pathway involving S-sulfocysteine as intermediate have been detected. Investigations on cyteine and methionine requiring mutants revealed independent regulation of O-acetylserine sulfhydrylase by endogeneous cysteine and methionine pools. The reaction catalysed by O-acetylserine sulfhydrylase is postulated as the only anabolic pathway of cysteine biosynthesis in A. nidulans.
...
PMID:Cysteine biosynthesis in Aspergillus nidulans. 110 3

Gamma-Glutamyl-cysteine synthetase is inhibited by glutathione under conditions similar to those which prevail in vivo, thus strongly suggesting a physiologically significant feedback mechanism. Inhibition by glutathione, which is not allosteric, appears to involve the binding of glutathione to the glutamate site of the enzyme as well as to another enzyme site; the latter binding appears to require a sulfhydryl group since ophthalmic acid (gamma-glutamyl-alpha-aminobutyryl-glycine) is only a weak inhibitor. The finding that glutathione regulates its own synthesis by inhibiting synthesis of gamma-glutamyl-cysteine appears to explain observations on patients with 5-oxoprolinuria, who were shown to have a block in the gamma-glutamyl cycle consisting of a marked deficiency of glutathione synthetase and consequently of glutathione. These patients produce greater than normal amounts of gamma-glutamyl-cysteine, which is converted by the action of gamma-glutamyl cyclotransferase to 5-oxoproline; production of the latter compound exceeds the capacity of 5-oxoprolinase to convert it to glutamate. The apparent Km value for L-cysteine for gamma-glutamyl-cysteine synthetase (0.35 mM) is not far from intracellular concentrations of L-cysteine suggesting that the availability of L-cysteine may also play a role in the regulation of glutathione synthesis.
...
PMID:Regulation of gamma-glutamyl-cysteine synthetase by nonallosteric feedback inhibition by glutathione. 111 10

1. The maximum activities of the enzymes for the biosynthesis of GSH (gamma-glutamyl-cysteine synthetase and GSH synthetase) have been assayed in high GSH and low GSH erythrocytes from Tasmanian Merino and Finnish Landrace sheep. 2. For the Merinos, the activities (mumol product/g haemoglobin per min +/- S.E.M. (n)) in the high and low GSH erythrocytes respectively were: gamma-glutamyl-cysteine synthetase: 0.776 +/- 0.065 (11) and 0.375 +/- 0.063 (13); and GSH synthetase: 0.069 +/- 0.003 (11) and 0.066 +/- 0.002 (13). 3. For the Finnish Landrace sheep the activities in the high and low GSH erythrocytes respectively were: gamma-glutamyl-cysteine synthetase: 0.595 +/- 0.063 (12) and 0.555 +/- 0.033 (10) and gamma-glutamyl-cysteine synthetase: 0.073 +/- 0.002 (12) and 0.070 +/- 0.002 (10). 4. gamma-Glutamyl-cysteine synthetase was markedly inhibited by physiological GSH concentrations. No evidence was found for the presence of an inhibitor of GSH biosynthesis (other than GSH) in low GSH erythrocytes from Finnish Landrace sheep. 5. Although for the Merinos the low GSH trait can be explained in terms of a diminished activity of gamma-glutamyl-cysteine synthetase, no such explanation is tenable for the Finnish Landrace sheep.
...
PMID:GSH biosynthesis in glutathione deficient erythrocytes from Finnish landrace and Tasmanian merino sheep. 117 55

59FeCl3 was used to measure red cell life span in GSH-low type sheep to the Tasmanian Merino breed, whose GSH deficiency is due to a diminished activity of gamma-glutamyl cysteine synthetase. The 59Fe survival slopes fell within normal limits, indicating that red cells with this type of GSH deficiency do not have a shortened life span.
...
PMID:The life span of glutathione-deficient red cells in Tasmanian Merino sheep. 121 91

The primary metabolic defect in 5-oxoprolinuria (pyroglutamic aciduria) is the lack of glutathione synthetase. The mechanism of the concomitant overproduction of 5-oxoproline was studied using cell-free extracts of erythrocytes from control individuals and from patients with 5-oxoprolinuria. Such extracts catalyzed the synthesis of 5-oxoproline from L-glutamate. Addition of ATP, Mg ions and alpha-aminobutyrate was needed for optimal activity. The conversion of glutamate to 5-oxoproline occurred in two steps, catalyzed by gamma-glutamyl-cysteine synthetase and gamma-glutamyl cyclotransferase, respectively. Extracts of erythrocytes from control subjects and patients with 5-oxoprolinuria had identical capacity to synthesize 5-oxoproline. The conversion of glutamate to 5-oxoproline was markedly inhibited by reduced glutathione, which exerted its effect on the gamma-glutamyl-cysteine synthetase step. The following mechanism is postulated for the overproduction of 5-oxoproline in 5-oxoprolinuria: the deficiency of glutathione synthetase causes a lack of glutathione which is an essential feed-back inhibitor in the initial step of its biosynthesis. Therefore gamma-glutamyl-cysteine is produced in excessive amounts and it is subsequently converted to 5-oxoproline (and cysteine) by gamma-glutamyl cyclotransferase. This overproduction of 5-oxoproline exceeds the capacity of the 5-oxoprolinase and 5-oxoproline accumulates in body fluids.
...
PMID:On the mechanism of 5-oxoproline overproduction in 5-oxoprolinuria. 126 Oct 42

This study was carried out to investigate the mechanism of Rifampicin (RIF) induced glutathione (GSH) depletion in M. smegmatis. RIF at various concentrations decreased the activities of gamma glutamyl cysteine synthetase (GGCS) and GSH synthetase. Maximum decrease in the activities of biosynthetic enzymes of GSH was observed when 15 micrograms RIF ml-1 medium was incorporated in the growth medium before performing inoculations. The activity of GGCS was also decreased when three day grown M. smegmatis was exposed to 60 micrograms RIF ml-1 medium for a period of 6 h and 9 h. RIF did not alter the activity of gamma glutamyl transferase. The results of the present study demonstrate that the depletion caused by RIF in cellular GSH is due to its decreased biosynthesis whereas its degradation is not affected in M. smegmatis.
...
PMID:Inhibition of cellular glutathione biosynthesis by rifampicin in Mycobacterium smegmatis. 135 83

Platinum-based chemotherapy has led to an improvement in complete response rates and duration of median remission, but has only given a modest improvement in overall survival in patients with advanced ovarian cancer. Chemotherapy will in the future focus upon: (1) improving the complete remission rate with new induction regimens; (2) identifying strategies capable of converting partial remission into complete remission; (3) preventing or delaying recurrences in patients who do achieve a complete remission; (4) identifying mechanisms of antineoplastic drug resistance and pharmacologic techniques capable of reversing drug resistance. Among the treatment approaches being utilized are high-dose chemotherapy with autologous bone marrow transplantation, development of new chemotherapeutic regimens which include Taxol and hexamethylmelamine, and intraperitoneal chemotherapy. In addition, our understanding of the mechanisms of antineoplastic drug resistance has led to the development of novel therapeutic approaches. It has been demonstrated that resistance to platinum and alkylating agents is associated with both increased concentrations of cellular glutathione (GSH) as well as an increased capacity of tumor cells to repair damage to DNA. Inhibition of GSH biosynthesis with buthionine sulfoximine (BSO), a synthetic inhibitor of the enzyme gamma glutamyl cysteine synthetase, has led to the potentiation of alkylating agent activity in vitro and in vivo. A phase I trial of BSO plus melphalan is currently in progress and a trial of BSO plus carboplatin is planned. Inhibition of the DNA repair process with aphidicolin potentiates the cytotoxicity of cisplatin in drug-resistant tumor cells. Clinical trials of aphidicolin plus cisplatin await the completion of ongoing phase I trials of aphidicolin.
...
PMID:Role of chemotherapy in the future treatment of ovarian cancer. 135 5

The effect of dietary polyunsaturated fatty acids (PIFA) upon the content of reduced glutathione (GSH) of the kidney was studied in 32 male Wistar rats. Two equal size groups were fed diets supplemented with either 10% or 18% corn oil. Sixteen hours before death, half of each experimental group was submitted to fasting. The content of GSH and the activity of gamma glutamyl transpeptidase (GGTP) and gamma glutamyl cysteine synthetase was determined in kidney tissue. Fasting led to a reduction of GSH from 3.21 +/- 0.54 to 1.25 +/- 0.20 mumol per gm in the group fed 10%. PIFA. Equivalent figures for the group fed 18% PIFA were 3.49 +/- 0.54 and 0.49 +/- 0.08, respectively. GGTP activity increased significantly after fasting but no differences were observed according to level of PIFA intake. The exaggerated reduction of GSH during fasting after a high PIFA intake may expose the animals to risk of cell damage induced by peroxides or other oxidating agents.
...
PMID:[Effect of dietary polyunsaturated fatty acids on the content and metabolism of glutathione in rat kidney]. 136 17

O-Acetylserine (thiol) lyase, the last enzyme in the cysteine biosynthetic pathway, was purified to homogeneity from spinach leaf chloroplasts. The enzyme has a molecular mass of 68,000 and consists of two identical subunits of Mr 35,000. The absorption spectrum obtained at pH 7.5 exhibited a peak at 407 nm due to pyridoxal phosphate, and addition of O-acetylserine induced a considerable modification of the spectrum. The pyridoxal phosphate content was found to be 1.1 per subunit of 35,000, and the chromophore was displaced from the enzyme by O-acetylserine, leading to a progressive inactivation of the holoenzyme. Upon gel filtration chromatography on Superdex 200, part of the chloroplastic O-acetylserine (thiol) lyase eluted in association with serine acetyltransferase at a position corresponding to a molecular mass of 310,000 (such a complex called cysteine synthase has been characterized in bacteria). The activity of O-acetylserine (thiol) lyase was optimum between pH 7.5 and 8.5. The apparent Km for O-acetylserine was 1.3 mM and for sulfide was 0.25 mM. The calculated activation energy was 12.6 kcal/mol at 10 mM O-acetylserine. The overall amino-acid composition of spinach chloroplast O-acetylserine (thiol) lyase was different than that determined for the same enzyme (cytosolic?) obtained from a crude extract of spinach leaves. A polyclonal antibody prepared against the chloroplastic O-acetylserine (thiol) lyase exhibited a very low cross-reactivity with a preparation of mitochondrial matrix and cytosolic proteins suggesting that the chloroplastic isoform was distinct from the mitochondrial and cytosolic counterparts.
...
PMID:Purification and characterization of O-acetylserine (thiol) lyase from spinach chloroplasts. 137 15


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---