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

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Query: EC:2.3.3.1 (citrate synthase)
4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Key enzyme activities of glycolysis, the pentose-phosphate pathway, the Krebs' cycle and glutaminolysis were measured in lymphocytes obtained from the control (CC), thioglycollate-injected (TG) and Walker 256 tumour-implanted (WT) groups, non-immune and immune inflammatory stimuli, respectively. The rates of incorporation of [2-14C]-thymidine and [5-3H]-uridine into cultured lymphocytes were also determined. The results indicated that the rates of both [2-14C]-thymidine and [5-3H]-uridine incorporation were enhanced in lymphocytes obtained from thioglycollate-injected (by an average of 80 per cent) and tumour-implanted animals (by 2.4-fold) as compared to control rats. Lymphocyte hexokinase activity diminished both in the TG (23 per cent) and WT (61 per cent) groups, whereas glucose 6-phosphate dehydrogenase activity was not altered due to the non-immune inflammatory stimulus, being reduced (23 per cent) in WT rats as compared to CC. The activity of lymphocyte citrate synthase was lowered by thioglycollate (39 per cent) and tumour-implantation (46 per cent). In contrast, glutaminase activity was augmented in lymphocytes from the TG (41 per cent) and was not modified in the WT groups. Taken as a whole, the presence of the Walker 256 tumour did not affect the capacity for glutamine utilization but depressed glucose metabolism in these cells. On the other hand, the non-immune inflammatory stimulus suppressed the activities of glycolysis and the Krebs' cycle and enhanced that of glutaminolysis in lymphocytes.
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PMID:Thioglycollate stimulus modifies lymphocyte metabolism and proliferation. A comparison with lymphocyte activation by Walker 256 tumour implantation. 827 49

Diabetic subjects present high susceptibility to infections but the mechanisms involved are not fully known. Macrophages and lymphocytes utilize glucose and glutamine at high rates and these metabolites are important for the function of these cells. The present study examines the activities of key metabolic enzymes in macrophages and lymphocytes obtained from alloxan-diabetic Wistar rats (10 weeks old, 7 rats each group). Since the enteral diet was enriched with omega-6 polyunsaturated fatty acids (PUFA), the effect of these fatty acids was also investigated in the same animals. Diabetes caused a marked decrease of hexokinase activity (48%; 274.23 +/- 18.43 vs 143.29 +/- 10.35 units for control vs diabetic rats) in macrophages and of citrate synthase and glucose-6-phosphate dehydrogenase activities (70%; 321.76 +/- 9.18 vs 96.25 +/- 5.43 units for citrate synthase and 89.43 +/- 2.33 vs 23.13 +/- 1.09 units for G6PDh for control vs diabetic rats) in mesenteric lymph node lymphocytes. A PUFA-rich diet given for 6 weeks enhanced hexokinase activities by 30% (274.23 +/- 18.43 vs 342.48 +/- 15.39, balanced vs PUFA-rich diets for normal and 143.29 +/- 10.35 vs 189.67 +/- 9.57 for diabetic rats) and reduced citrate synthase activities by 43% (30.31 +/- 1.73 vs 17.42 +/- 0.95, balanced vs PUFA-rich diets for normal and 29.34 +/- 1.23 vs 16.73 +/- 1.02 for diabetic rats) in macrophages, and reduced (< 50%; 59.67 +/- 3.45 vs 48.87 +/- 3.37 for hexokinase and 321.76 +/- 2.33 vs 161.66 +/- 9.97 for citrate synthase, balanced vs PUFA-rich diets) the activities of both enzymes in lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of a polyunsaturated fatty acid-rich diet on macrophage and lymphocyte metabolism of diabetic rats. 829 16

The human leukaemic cell line HL60 undergoes differentiation to granulocyte-like cells in response to dimethylsulphoxide (DMSO). The rates of glucose and glutamine utilization were studied in HL60 cells that were either undifferentiated or fully differentiated by 9 days exposure to DMSO. Differentiation did not alter the rate of utilization of exogenous glucose, approximately 75% of which was converted to lactate in each case. The activities of hexokinase, phosphofructokinase, pyruvate kinase and citrate synthase were similarly unaffected. In contrast, the activity of the oxidative segment of the pentose-phosphate pathway was enhanced by differentiation, and no glycogen synthase activity could be detected. These observations are consistent with the significantly lower content of glycogen, the increased activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase and the increased oxidation of [1-14C] glucose relative to [6-14C] glucose in the differentiated cells. Glucose utilization was depressed by exogenous glutamine but, at the same time, glutamine utilization was enhanced by glucose in both cell types; these reciprocal effects were more pronounced in the undifferentiated HL60 cells. Glucose utilization may be depressed in the presence of glutamine as a result of the allosteric inhibition of a rate-limiting step of glycolysis (eg. phosphofructokinase). In spite of having glutaminase activity twice that of their differentiated counterparts, the uptake of glutamine by undifferentiated HL60 cells was low, especially when it was the sole substrate. The stimulation of glutaminolysis by glucose may be due to activation of mitochondrial glutamine transport. A large proportion of the glutamine utilized by both cells contributed to a net accumulation of glutamate, aspartate and alanine, whilst up to 35% was oxidized to CO2. In contrast, almost all of the glucose utilized was converted to lactate and very little was oxidized. The high rates of glycolysis and glutaminolysis observed before and after differentiation may not contribute primarily to energy production but may supply, in undifferentiated cells, substrates for biosynthetic processes that generate nucleic acid precursors or, in the case of differentiated cells which synthesize reactive oxygen intermediates, substrates that maintain NADP in a reduced state.
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PMID:Glycolytic, glutaminolytic and pentose-phosphate pathways in promyelocytic HL60 and DMSO-differentiated HL60 cells. 833 14

1. The metabolism of glucose, glutamine and ketone-bodies was studied in the small intestine of rats after 5 days of hyperthyroidism. 2. Portal-drained visceral bloodflow increased by 20.1% (P < 0.05) in hyperthyroid rats and was accompanied by a decrease in the arteriovenous concentration difference of glutamine (25.7%, P < 0.05), glutamate (22.0%, P < 0.05), alanine (20.9%, P < 0.05) and ammonia (20.6%, P < 0.05) and an increase in that of glucose (27.2%, P < 0.05), lactate (28.9%, P < 0.05) and ketone-bodies (163.2%, P < 0.001). 3. The gut of hyperthyroid rats showed increased rates of extraction of glucose, lactate and ketone-bodies. 4. Enterocytes isolated from hyperthyroid rats showed increased rates of utilization of glucose and ketone-bodies but that of glutamine were decreased. 5. The maximal activities of hexokinase, 6-phosphofructokinase, pyruvate kinase, citrate synthase and oxoglutarate dehydrogenase were increased (by 13.7-36.2%) in intestinal mucosal scrapings of hyperthyroid rats, whereas the activity of glutaminase was decreased (22.1-31.4%). 6. It is concluded that hyperthyroidism increases the rates of utilization of glucose and ketone-bodies but decreases that of glutamine (both in vivo and in vitro) by the epithelial cells of the small intestine.
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PMID:Effects of hyperthyroidism on glucose, glutamine and ketone-body metabolism in the gut of the rat. 846 60

Several studies have shown that thyroid hormones are able to influence selected immune responses such as cell mediated immunity, differentiation of B lymphocytes and the activity of NK cells. These hormones can also regulate the metabolism of glucose and glutamine in rat macrophages and their effects seem to occur mainly through the Krebs cycle. Alterations in the hexokinase, citrate synthase, glucose-6-phosphate dehydrogenase and glutaminase activities in lymphocytes from patients with Graves' disease, either untreated or on methimazole (MMI) therapy were investigated. Experiments were also done in vitro to determine the activities of these enzymes in normal lymphocytes cultured for 24 h in the presence of MMI T3 and T4 using concentrations close to the physiological. Changes in the conversion of [U-14C]-glucose and [U-14C]-glutamine to 14CO2 as caused by the addition of MMI, T3 or T4 to the culture medium were also evaluated. The results indicate that high levels of thyroid hormones might stimulate the metabolism of glucose and glutamine for a short period of time but, if the stimulus is maintained, the utilization of glutamine by lymphocytes is then suppressed. Moreover, MMI does affect lymphocyte metabolism but the significance of this finding for its immunosuppressive effect remains to be examined.
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PMID:Metabolism of glucose and glutamine in lymphocytes from Graves' hyperthyroid patients: influence of methimazole treatment. 864 Sep 58

The rabbit kidney does not readily metabolize but synthesizes glutamine at high rates by pathways that remain poorly defined. Therefore, the metabolism of variously labeled [13C]- and [14C]glutamates has been studied in isolated rabbit kidney tubules with and without acetate. CO2, glutamine, and alanine were the main carbon and nitrogenous end products of glutamate metabolism but no ammonia accumulated. Absolute fluxes through enzymes involved in glutamate metabolism, including enzymes of four different cycles operating simultaneously, were assessed by combining mainly the 13C NMR data with a new model of glutamate metabolism. In contrast to a previous conclusion of Klahr et al. (Klahr, S., Schoolwerth, A. C., and Bourgoignie, J. J. (1972) Am. J. Physiol. 222, 813-820), glutamate metabolism was found to be initiated by glutamate dehydrogenase at high rates. Glutamate dehydrogenase also operated at high rates in the reverse direction; this, together with the operation of the glutamine synthetase reaction, masked the release of ammonia. Addition of acetate stimulated the operation of the "glutamate --> alpha-ketoglutarate --> glutamate" cycle and the accumulation of glucose but reduced both the net oxidative deamination of glutamate and glutamine synthesis. Acetate considerably increased flux through alpha-ketoglutarate dehydrogenase and citrate synthase at the expense of flux through phosphoenolpyruvate carboxykinase; acetate also caused a large decrease in flux through alanine aminotransferase, pyruvate dehydrogenase, and the "substrate cycle" involving oxaloacetate, phosphoenolpyruvate, and pyruvate.
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PMID:The rabbit kidney tubule simultaneously degrades and synthesizes glutamate. A 13C NMR study. 903 May 22

A combined isotopic steady state and in vivo isotopic non-steady state analysis was used to calculate tricarboxylic acid cycle flux in livers of anesthetized rats infused with ethanol. In vivo 13C NMR spectroscopy was used to non-invasively observe label turnover of [4-13C]glutamate, [4-13C]glutamine, and [2-13C]glutamate/glutamine in liver following a bolus intravenous infusion of [2-13C]ethanol. The isotopic steady state analysis of [2-13C], [3-13C], and [4-13C]glutamate isotopomers (Malloy, C. R., Sherry, A. D., and Jeffrey, F. M. H. (1988) J. Biol. Chem. 263, 6964-6971) in liver extracts was used to indirectly calculate the anaplerotic flux (0.90 +/- 0.07 x citrate synthase flux) and [2-13C]acetyl-CoA fractional enrichment (51.4 +/- 3.4%). The [4-13C]glutamate, [4-13C]glutamine, and [2-13C]glutamate fractional enrichments determined in liver extracts were 23.0 +/- 1.1, 17.2 +/- 1.5, and 7.7 +/- 0.5%, respectively. These data in addition to blood [2-13C]acetate and [4-13C]glutamine enrichment time course data were used in conjunction with a metabolic steady state mathematical analysis designed to account for liver glutamate and glutamine label dilution as a consequence of glutamine exchange with blood to calculate the tricarboxylic acid (tca) cycle flux (Vtca = 0.33 +/- 0.09 micromol/g wet weight/min) in liver. In summary, It is possible to detect 13C labeling of glutamate and glutamine in liver via non-invasive 13C NMR. Additionally, the in vivo 13C labeling kinetics of glutamate and glutamine in liver and glutamine in blood may be used to calculate the liver tricarboxylic acid cycle flux.
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PMID:In vivo 13C NMR measurements of hepatocellular tricarboxylic acid cycle flux. 957 66

The effects of ketone bodies on brain metabolism of glutamate and GABA were studied in three different systems: synaptosomes, cultured astrocytes and the whole animal. In synaptosomes the addition of either acetoacetate or 3-OH-butyrate was associated with diminished consumption of glutamate via transamination to aspartate and increased formation of labelled GABA from either L-[2H5-2,3,3,4, 4]glutamine or L-[15N]glutamine. There was no effect of ketone bodies on synaptosomal GABA transamination. An increase of total forebrain GABA and a diminution of aspartate was noted when mice were injected intraperitoneally with 3-OH-butyrate. In cultured astrocytes the addition of acetoacetate to the medium was associated with a significantly enhanced rate of citrate production and with a diminution in the rate of conversion of [15N]glutamate to [15N]aspartate. These data are consistent with the hypothesis that the metabolism of ketone bodies to acetyl-CoA results in a diminution of the pool of brain oxaloacetate, which is consumed in the citrate synthetase reaction (oxaloacetate + acetyl-CoA --> citrate). As less oxaloacetate is available to the aspartate aminotransferase reaction, thereby lowering the rate of glutamate transamination, more glutamate becomes accessible to the glutamate decarboxylase pathway, thereby favoring the synthesis of GABA.
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PMID:Ketone bodies and brain glutamate and GABA metabolism. 977 72

Examination of the ways side-chain carboxylate and amide groups in high-resolution protein crystal structures form hydrogen bonds with main-chain atoms reveals that the most common category is a two-hydrogen-bond four to five residue motif with an aspartate or asparagine (Asx) at the first residue, for which we propose the name Asx-motif. Similar motifs with glutamate or glutamine residues at that position are rare. Asx-motifs occur typically as (1) a common feature of the N termini of alpha-helices called the Asx N-cap motif; (2) an independent motif, usually a beta-turn with an appropriately hydrogen-bonded Asx as the first residue; and (3) a motif incorporated in a beta-bulge loop. Asx-motifs are common, there being just under two-and-a-half in an average-sized protein subunit; of these, about 55 % are Asx N-cap motifs. Because they occur often in many situations, it seems that these motifs have an inherent propensity to form on their own rather than just being a feature stabilised at the end of a helix. Asx-motifs also occur in functionally interesting situations in aspartyl proteases, citrate synthase, EF hands, haemoglobins, lipocalins, glutathione reductase and the alpha/beta hydrolases.
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PMID:A natural grouping of motifs with an aspartate or asparagine residue forming two hydrogen bonds to residues ahead in sequence: their occurrence at alpha-helical N termini and in other situations. 1006 20

Although glutamine synthesis has a major role in the control of acid-base balance and ammonia detoxification in the kidney of herbivorous species, very little is known about the regulation of this process. We therefore studied the influence of acetate, which is readily metabolized by the kidney and whose metabolism is accompanied by the production of bicarbonate, on glutamine synthesis from variously labelled [(13)C]alanine and [(14)C]alanine molecules in isolated rabbit renal proximal tubules. With alanine as sole exogenous substrate, glutamine and, to a smaller extent, glutamate and CO(2), were the only significant products of the metabolism of this amino acid, which was removed at high rates. Absolute fluxes through the enzymes involved in alanine conversion into glutamine were assessed by using a novel model describing the corresponding reactions in conjunction with the (13)C NMR, and to a smaller extent, the radioactive and enzymic data. The presence of acetate (5 mM) led to a large stimulation of fluxes through citrate synthase and alpha-oxoglutarate dehydrogenase. These effects were accompanied by increases in the removal of alanine, in the accumulation of glutamate and in flux through the anaplerotic enzyme pyruvate carboxylase. Acetate did not alter fluxes through glutamate dehydrogenase and glutamine synthetase; as a result, acetate did not change the accumulation of ammonia, which was negligible under both experimental conditions. We conclude that acetate, which seems to be an important energy-provider to the rabbit renal proximal tubule, simultaneously traps as glutamate the extra nitrogen removed as alanine, thus preventing the release of additional ammonia by the glutamate dehydrogenase reaction.
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PMID:Acetate stimulates flux through the tricarboxylic acid cycle in rabbit renal proximal tubules synthesizing glutamine from alanine: a 13C NMR study. 1047 67


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