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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
Biochem Mol Biol Int 1993 Apr
PMID:Glycolytic, glutaminolytic and pentose-phosphate pathways in promyelocytic HL60 and DMSO-differentiated HL60 cells. 833 14

It was previously shown that polyunsaturated and saturated fatty acid rich diets affected metabolic and functional changes in macrophages and a variety of immune tissues (thymus, mesenteric lymph nodes and spleen). This study reports metabolic and functional changes in peritoneal macrophages and lymphocytes of Walker-256 ascites cell tumour-bearing rats which were fed (a) normal balanced diet (3% fat), (b) diet enriched (15% fat) with polyunsaturated fatty acids or (c) diet fortified (15% fat) with saturated fatty acids. Neither of the fatty acid enriched diets affected macrophage migration following tumour cell implantation and ascitic cell growth. However both of these fortified fatty acid regimes enhanced the production of H2O2 by macrophages and lymphocytes. The maximum catalytic capacities of hexokinase, glutaminase, glucose-6-phosphate dehydrogenase and glutathione peroxidase were measured in resident and tumour activated macrophages and lymphocytes obtained from rats fed the three fatty acid dietary regimes during seven days of tumour ascites cell growth. Tumour growth caused an increase in the activities of all of the above enzymes in macrophages irrespective of the fatty acid composition of the diet and notably decreased, independent of dietary fatty acid composition, the activities of the enzymes in lymphocytes. Only glutaminase activity in the lymphocytes of tumour bearing animals fed an unsaturated fatty acid-rich diet was not reduced, but was increased by 78%. Moreover macrophages from control rats fed an enriched polyunsaturated fatty acid diet had increased hexokinase activity (21%), decreased glutaminase (48%) and citrate synthase (decreased 41%) relative to the activities of these enzymes in macrophages of animals maintained on a balanced fatty acid diet. The feeding of both fatty acid rich diets did not modify the pattern of lymphocyte responses during the growth of tumour cells in these animals. None of the fatty acid diets modified the growth rate nor the yield of tumour cells in the peritoneal cavity.
Biochem Mol Biol Int 1993 Jan
PMID:Effects of various dietary fatty acids on enzyme activities of carbohydrate and glutamine metabolism and the metabolic response of lymphocytes and macrophages during Walker-256 ascites cell tumour growth in rats. 849 May 66

Carbamoylphosphate is a common intermediate in the metabolic pathways leading to the biosynthesis of arginine and pyrimidines. The amino acid sequences of all available proteins that catalyze the formation of carbamoylphosphate were retrieved from Genbank and aligned to estimate their mutual phylogenetic relations. In gram-negative bacteria carbamoylphosphate is synthesized by a two-subunit enzyme with glutaminase and carbamoylphosphate synthetase (CPS) activity, respectively. In gram-positive bacteria and lower eukaryotes this two-subunit CPS has become dedicated to arginine biosynthesis, while in higher eukaryotes the two subunits fused and subsequently lost the glutaminase activity. The CPS dedicated to pyrimidine synthesis is part of a multifunctional enzyme (CPS II), encoding in addition dihydroorotase and aspartate transcarbamoylase. Evidence is presented to strengthen the hypothesis that the two "kinase" subdomains of all CPS isozymes arose from a duplication of an ancestral gene in the progenote. A further duplication of the entire CPS gene occurred after the divergence of the plants and before the divergence of the fungi from the eukaryotic root, generating the two isoenzymes involved in either the synthesis of arginine or that of pyrimidines. The mutation rate was found to be five- to tenfold higher after the duplication than before, probably reflecting optimization of the enzymes for their newly acquired specialized function. We hypothesize that this duplication arose from a need for metabolic channeling for pyrimidine biosynthesis as it was accompanied by the tagging of the CPS gene with the genes for dihydroorotase and aspartate transcarbamoylase, and as the duplication occurred independently also in gram-positive bacteria. Analysis of the exon-intron organization of the two "kinase" subdomains in CPS I and II suggests that ancient exons may have comprised approx. 19 amino acids, in accordance with the prediction of the "intron-early" theory.
J Mol Evol 1995 Dec
PMID:Evolutionary relationships of the carbamoylphosphate synthetase genes. 858 26

A large body of evidence from experimental studies has documented that n-3 fatty acids can modify a variety of cell functions and disease states. As lymphocytes and macrophages are important cells for the development of the inflammatory and non-inflammatory immune response and are known to utilize high rates of glucose and glutamine, we have evaluated the effect of n-3 PUFA rich diet on the metabolisation of glucose and glutamine these cells, as well as the effect of one such diet upon the proliferative response of lymphocytes and the phagocytic capacity and hydrogen peroxide production by macrophages. The diet provoked an increase in the flux of glucose through the Krebs cycle in macrophages as well as a reduction in G6PDh and glutaminase activity in these cells. Lymphocytes from n-3 PUFA rich diet-fed rats showed a reduction in glucose and glutamine decarboxylation. Taken together the data show that, at least in part, the functional changes observed in macrophages and lymphocytes from n-3 PUFA-rich diet fed rats are related to the effect of this diet upon glucose and glutamine metabolism, leading to immunosuppression.
Biochem Mol Biol Int 1996 Nov
PMID:The effect of N-3 PUFA rich diet upon macrophage and lymphocyte metabolism and function. 895 42

Glutamine is utilized as an energy substrate in preimplantation mouse embryos. Glutaminase is the enzyme responsible for the conversion of glutamine to glutamic acid, which then enters the trichloro acetic acid (TCA) cycle as alpha-ketoglutarate. Glutaminase enzyme activity was assessed in preimplantation embryos that developed in vivo, and glutaminase RNA expression was examined in embryos that developed in vivo or were cultured in CZB medium to various preimplantation stages between 1-cell and blastocyst. Glutaminase activity in 1-8-cell-stage mouse embryos that developed in vivo ranged from 0.009-0.01 U/mg protein (2.39-2.95 x 10(-7) U per embryo) and increased 3-4 fold to 0.034 U/mg protein (8.13 x 10(-7) U per embryo) at the blastocyst stage. Relative stage-specific expression of glutaminase RNA was assessed by reverse transcription polymerase chain reaction (RT-PCR) in embryos that developed both in vivo and in CZB culture. In vivo, glutaminase RNA was expressed at the 1-cell stage, declined to 23% of 1-cell levels at the early 2-cell stage, and reaccumulated from late 2-cell through blastocyst stage, where it reached a high of 204% of 1-cell levels. CZB-cultured embryos exhibited a similar pattern of developmental RNA expression, declining to 30% of 1-cell levels at the early 2-cell stage, and increasing RNA expression at the blastocyst stage to 191% of the 1-cell level.
Mol Reprod Dev 1997 Jul
PMID:Analysis of glutaminase activity and RNA expression in preimplantation mouse embryos. 917 Jan 4

Although the liver was long known to play a major role in the uptake, synthesis, and disposition of glutamine, metabolite balance studies across the whole liver yielded apparently contradictory findings suggesting that little or no net turnover of glutamine occurred in this organ. Efforts to understand the unique regulatory properties of hepatic glutaminase culminated in the conceptual reformulation of the pathway for glutamine synthesis and turnover, especially as regards the role of sub-acinar distribution of glutamine synthetase and glutaminase. This chapter describes these processes as well as the role of glutamine in hepatocellular hydration, a process that is the consequence of cumulative, osmotically active uptake of glutamine into cells. This topic is also examined in terms of the effects of cell swelling on the selective stimulation or inhibition of other far-ranging cellular processes. The pathophysiology of the intercellular glutamine cycle in cirrhosis is also considered.
Adv Enzymol Relat Areas Mol Biol 1998
PMID:Hepatic glutamine transport and metabolism. 955 51

The concentration of mRNA within the intestinal mucosa is usually measured by either Northern blot analysis or semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). However, these methods are limited by a lack of valid internal controls, low sensitivity, and large differences in the concentration of the internal control and target gene. The authors present an alternative method using competitive RT-PCR to measure glutaminase mRNA in isolated enterocytes.
Mol Cell Probes 1998 Oct
PMID:Quantitation of glutaminase mRNA in enterocytes using competitive RT-PCR. 977 61

The distribution of glutaminase expression in a uricotelic species, the chicken, has been examined using cDNA probes to the rat isozymes. The results suggest that chickens do not possess a glutaminase isozyme equivalent to the liver-type isozyme of mammalian liver. Measurements of enzymic activity also showed very low glutaminase activity in chicken liver. Extra-hepatic tissues in the chicken do express a glutaminase isozyme mRNA which is detected by rat kidney-type glutaminase cDNA. The abundance of this mRNA was highest in kidney and breast muscle and relatively abundant in brain, spleen and adipose tissue. Chicken small intestine expressed relatively low levels of the mRNA. The high level of glutaminase mRNA in chicken pectoralis muscle was accompanied by high glutaminase enzymic activity. In contrast, in mixed leg muscle glutaminase mRNA was barely detectable by Northern blot and glutaminase activity was relatively low. Starvation for 48 h resulted in a slight decrease in the activity of glutaminase in pectoralis muscle, but a large decrease in the relative abundance of the mRNA. The results suggest that in the chicken, hepatic glutamine hydrolysis is not quantitatively important, but skeletal muscle may be a major site of glutamine catabolism.
Comp Biochem Physiol B Biochem Mol Biol 1998 Jun
PMID:Distribution of phosphate-activated glutaminase isozymes in the chicken: absence from liver but presence of high activity in pectoralis muscle. 978 97

Various cDNAs that encode overlapping portions of the full-length human brain glutaminase (GA) cDNA were cloned and sequenced. The overall nucleotide sequence of hGA has a very high degree of identity with that of the rat kidney-type GA cDNA (77.4%) and the known portion of the cDNA that encodes the 5.0-kb porcine GA mRNA (81.1%). The identity is even more remarkable at the amino acid level, particularly in the C-terminal half where the three proteins share a 99.7% sequence identity. The hGA cDNA encodes a 73,427-Da protein that contains an N-terminal mitochondrial targeting signal and retains the primary proteolytic cleavage site characterized for the cytosolic precursor of the rat renal mitochondrial glutaminase. The entire coding region was assembled through the use of unique restriction sites and cloned into a baculovirus. Sf9 cells infected with the recombinant virus express high levels of properly processed and active glutaminase. Thus, expression of the isolated hGA cDNA should provide a means to purify large amounts of the mitochondrial glutaminase, a protein that catalyzes a key reaction in the metabolism of glutamine and the synthesis of important excitatory and inhibitory neurotransmitters.
Brain Res Mol Brain Res 2000 Mar 10
PMID:Isolation, characterization and expression of a human brain mitochondrial glutaminase cDNA. 1071 15

The koji mold Aspergillus oryzae is able to produce glutaminase which converts glutamine to glutamic acid, one of the most important flavor components in soy sauce. We present here the isolation and the complete nucleotide sequence of the glutaminase- encoding gene from A. oryzae U212, an industrial strain used in Thailand. N-terminal and internal amino acid sequences were determined from purified glutaminase. A 700-bp fragment was amplified by PCR using oligonucleotide primers designed from partial amino acid sequences. This PCR fragment was used as a homologous probe for screening an A. oryzae genomic DNA library. RT-PCR showed that the gene contained seven short introns. Sequence analysis revealed an open reading frame that encodes a protein of 690 amino-acid residues with a predicted molecular mass of 76 kDa. The N-terminal and internal amino acid sequences of the deduced protein exactly matched the ones determined from the purified protein. Comparison of the amino acid sequence with glutaminase sequences from other origins showed that A. oryzae glutaminase shares little homology with those of bacteria, eukaryote and mammals. The A. oryzae glutaminase gene was expressed in A. nidulans to confirm the presence of a functional glutaminase gene in the cloned DNA. To our knowledge, this is the first reported glutaminase gene cloned from filamentous fungi.
J Mol Microbiol Biotechnol 2001 Oct
PMID:A new class of glutaminase from Aspergillus oryzae. 1154 78


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