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

As glutamine-dependent carbamoyl phasphate synthetase (CPS) activity in some organisms is composed of a glutaminase and an ammonium-dependent CPS, CPS- mutants in Neurospora crassa were examined for glutamine- and ammonium-dependent CPS activities. No evidence was found that the genetic location of these two functions were separable. This is discussed with reference to the close genetic proximity of the CPSpyr and aspartate carbamoyltransferase (ACT) structural gene (pyr-3) and the arg-2 gene which appears to specify a subunit responsible for glutamine utilisation in CPSarg.
Mol Gen Genet 1976 Dec 08
PMID:Glutamine utilization in both the arginine-specific and pyrimidine-specific carbamoyl phosphate synthase enzymes of eurospora crassa. 18 79

Glutamine-dependent carbamoyl-phosphate synthetase (EC 6.3.5.5) catalyzes the first step in de novo pyrimidine biosynthesis. The mammalian enzyme is part of a 240-kDa multifunctional protein which also has the second (aspartate carbamoyltransferase, EC 2.1.3.2), and third (dihydroorotase, EC 3.5.2.3) activities of the pathway. Shigesada et al. (Shigesada, K., Stark, G.R., Maley, J.A., and Davidson, J.N. (1985) Mol. Cell Biol. 175, 1-7) produced a truncated cDNA clone from a Syrian hamster cell line that contained most of the coding region for this protein. We have completed sequencing this clone, known as pCAD142. The cDNA insert contained all of the coding region for the glutaminase (GLN) and carbamyl phosphate synthetase (CPS) domains but lacked a short amino-terminal segment. By comparing the primary structure of the mammalian chimera to monofunctional proteins we have identified the borders of the functional domains. The GLN domain is 21 kDa, close to the size of the functionally similar polypeptide products of the Escherichia coli pabA and hisH genes. The domain has the three regions of homology common to trpG-type glutamine amidotransferases, as well as a fourth region specific to the carbamyl phosphate synthetases. The CPSase domain is similar to other reported CPSases in size (120 kDa), primary structure (37-67% amino acid identity), and homology between its amino and carboxyl halves. Analysis of the nucleotide and amino acid sequence identities among the various carbamyl phosphate synthetases suggests that the gene fusion which joined the GLN and CPS domains was an early event in the evolution of eukaryotic organisms and that the Saccharomyces cerevisiae enzyme consisting of separate subunits arose by defusion from an ancestral multifunctional protein.
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PMID:Mammalian carbamyl phosphate synthetase (CPS). DNA sequence and evolution of the CPS domain of the Syrian hamster multifunctional protein CAD. 197 79

Glutamate in glutamatergic neurons exists in a cytosolic pool, as well as a transmitter pool, which is assumed to be localized in synaptic vesicles. Transmitter glutamate released from glutamatergic neurons is taken up by both neurons and glial cells, giving rise to a flux of glutamate from neurons to astrocytes. In astrocytes, glutamine is formed from glutamate by the glial-specific enzyme glutamine synthetase (EC 6.3.1.2). Glutamine diffuses back to neurons, where glutamate is formed by phosphate-activated glutaminase (EC 3.5.1.2). However, this cycle is not stoichiometric, and glutamine obtained from glial cells cannot replenish all transmitter glutamate lost from neurons. 2-Oxoglutarate is another putative precursor for transmitter glutamate. Net synthesis of citric acid cycle intermediates is dependent on carbon dioxide fixation to pyruvate, catalyzed by pyruvate carboxylase (EC 6.4.1.1). Since this enzyme is exclusively glial, a net flow of citric acid cycle intermediates from glial cells to neurons probably exists. The quantitative contribution of each transmitter precursor may not be the same in different regions of the brain and may vary with the metabolic state of the neuron. The pool of transmitter glutamate is most likely regulated by the activity of glutamate-forming enzymes in the nerve terminal, and/or by uptake/release of glutamate and glutamate precursors through the synaptosomal plasma membrane.
Mol Chem Neuropathol 1990 Jan
PMID:Synthesis of transmitter glutamate and the glial-neuron interrelationship. 198 May 84

In situ hybridization histochemistry (ISHH) using synthetic oligonucleotide probes has been used to identify cells containing the mRNAs coding for glutaminase (GluT), aspartate aminotransferase (AspT) and glutamic acid decarboxylase (GAD). The distribution of GAD mRNA confirms previous descriptions and matches the distribution of GAD detected using specific antibodies. AspT mRNA is widely distributed in the brain, but is present at high levels in GABAergic neuronal populations, some that may be glutamatergic, and in a subset of neurons which do not contain significant levels of either GAD or GluT mRNA. Particularly prominent are the neurons of the magnocellular division of the red nucleus, the large cells in the deep cerebellar nuclei and the vestibular nuclei and neurons of the lateral superior olivary nucleus. GluT mRNA does not appear to be present at high levels in all GAD-containing neurons, but is seen prominently in many neuronal populations that may use glutamate as a neurotransmitter, such as neocortical and hippocampal pyramidal cells, the granule cells of the cerebellum and neurons of the dentate gyrus of the hippocampus. The heaviest labelling of GluT mRNA is seen in the lateral reticular nucleus of the medulla. ISHH using probes directed against the mRNAs encoding these enzymes may be an important technique for identifying glutamate and aspartate using neuronal populations and for examining their regulation in a variety of experimental and pathological circumstances.
Brain Res Mol Brain Res 1990 May
PMID:Distribution of messenger RNAs encoding the enzymes glutaminase, aspartate aminotransferase and glutamic acid decarboxylase in rat brain. 216 7

Mammalian liver possesses a unique isozyme of phosphate-activated glutaminase which plays an important role in the regulation of glutamine catabolism. Antibodies to hepatic glutaminase were used to screen a lambda gt11 rat liver cDNA library. One cDNA to hepatic glutaminase was identified. Changes in the relative abundance of hepatic glutaminase mRNA were determined by hybridization to this cDNA. The mRNA is found only in liver; it is not present prior to birth but its abundance increases dramatically at birth. The abundance of the mRNA is increased approximately 4-fold in diabetes. The sequence of the cDNA was compared to that recently published for kidney (brain)-type glutaminase (Banner, C., Hwang, J.-J., Shapiro, R.A., Wenthold, R.J., Nakatani, Y., Lampel, K.A., Thomas, J.W., Huie, D., and Curthoys, N.P. (1988) Mol. Brain Res. 3, 247-254). When the predicted amino acid sequences were compared a region of 123 amino acids with greater than 80% identity was found. The presence of scattered amino acid substitutions within stretches of identical amino acids suggests that the glutaminase isozymes are encoded by separate genes. This is the first demonstration of any similarity between the two glutaminases at the molecular level.
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PMID:Molecular cloning of a cDNA for rat hepatic glutaminase. Sequence similarity to kidney-type glutaminase. 219 54

Glutaminase mRNA levels increased over 3-fold relative to total RNA, poly(A)+ RNA, and beta-actin mRNA in neonatal rat cerebellar granule cells as the cells differentiated between days 3 and 8 in culture. In contrast, mRNA levels of another glutamate cycle enzyme, glutamine synthetase, remained constant. Glutaminase protein levels increased per cell more than 2-fold between days 3 and 8, and at least 3-fold by day 10 in these cells. The total amount of glutamate per cell increased about 40% during this period. Glutaminase induction paralleled the development of Ca2+-dependent glutamate release, and the formation of neurites, synaptic vesicles, and synapses. The induction of glutaminase in developing granule cells is consistent with a special role for glutaminase in the synthesis of neurotransmitter glutamate.
Brain Res Mol Brain Res 1989 Jul
PMID:Developmental induction of glutaminase in primary cultures of cerebellar granule cells. 257 Mar 41

The amino acid sequence of carbamyl phosphate synthetase (CPS) III from liver of spiny dogfish shark Squalus acanthias was deduced from the nucleotide sequence of its cDNA. Alignment of the derived amino acid sequence of CPS III with sequences of rat and frog CPS I and hamster CPS II reveals a high degree of amino acid identity, indicating that CPS III shares the same common ancestral genes as CPSs I and II. All of the CPSs examined show a high conservation of sequences in the adenine nucleotide binding domains and in residues that have been implicated in catalysis. The active-site cysteine residue required for glutamine-dependent activity by CPS II is preserved in the sequence of CPS III. Nevertheless, analysis of the protein sequences indicates that CPS III is more closely related to CPS I than to CPS II. The structure of CPS III, which is composed of a single polypeptide, is consistent with the view that CPS III evolved by fusion of separate genes coding for the glutaminase and synthetase domains of the enzyme and, like other CPSs, the synthetase domain evolved by duplication and fusion of an ancestral kinase gene. These results, together with the recent finding that frog CPS I retains the active site cysteine residue in the glutaminase domain required for glutamine-dependent activity, indicate that other amino acid substitutions critical for glutamine-dependent activity preceded loss of this catalytic cysteine residue. The results described here together with earlier biochemical evidence support the view that acetylglutamate and glutamine-dependent CPS III found in invertebrates and fish species represents an intermediate in the evolution of ancestral glutamine-dependent CPS II toward the acetylglutamate and ammonia-dependent CPS I of ureotelic terrestrial vertebrates.
J Mol Biol 1994 Oct 14
PMID:Carbamyl phosphate synthetase III, an evolutionary intermediate in the transition between glutamine-dependent and ammonia-dependent carbamyl phosphate synthetases. 793 37

In T. thermophila two forms of L-asparaginase (EC 3.5.1.1) were extracted and purified to near homogeneity which are associated with membranes. These two forms of L-asparaginase, I or II, act optimally at pH 8.6 and do not present any glutaminase or kinase activity. Both activities reach maximal values at the stationary phase of growth of T. thermophila. L-Asparaginases are solubilized by treatment of the particulates with 2% w/v Triton X-100 and then by sodium phosphate buffer pH 8.0. Both forms cross reacted with antibodies raised against T. pyriformis L-asparaginase and show isoelectric points 7.4 and 8.2. Among the metals tested, Ca2+ is the most effective in activating L-asparaginase I or II activity. Sorbitol alone up to 30% w/v in the assay mixture activates more than 10 x fold the activity of L-asparaginase II. Incubation of L-asparaginase I or II with increasing concentration of phospholipase C results in gradually loss of their activities. The relative effectiveness of a variety of phospholipids to reconstitute enzyme activity is presented as well.
Biochem Mol Biol Int 1994 Jan
PMID:Two forms of L-asparaginase in Tetrahymena thermophila. 801 91

The effect of aluminum on the metabolism of glutamate and glutamine in astrocytes was studied to provide information about a possible biochemical mechanism for aluminum neurotoxicity and its potential contribution to neurodegenerative disease. Exposure of cultured rat brain astrocytes for 3-4 d to 5-7.5 mM aluminum lactate increased glutamine synthetase activity by 100-300% and diminished glutaminase activity by 50-85%. Increased glutamine synthetase enzyme activity was accompanied by an elevated level of glutamine synthetase mRNA. Alterations in glutaminase and glutamine synthetase following aluminum exposure caused increased intracellular glutamine levels, decreased intracellular glutamate levels, and increased conversion of glutamate to glutamine and the release of the latter into the extracellular space. The results of these changes may alter the availability of neurotransmitter glutamate in vivo and may be a mechanism for the aluminum neurotoxicity observed in individuals exposed to the metal during dialysis procedures and other situations.
Mol Chem Neuropathol 1993 Aug
PMID:A glutamatergic mechanism for aluminum toxicity in astrocytes. 810 2

Pathophysiological concentrations of ammonia, both in vivo and in vitro, suppressed the oxidation of glutamate by rat cerebellar mitochondria. The transport of glutamate into mitochondria was either unaltered or enhanced during hyperammonemic states. Activities of mitochondrial enzymes, aspartate aminotransferase, alanine aminotransferase, glutamate dehydrogenase, glutaminase, and GABA-transaminase were suppressed during hyperammonemic states. Suppression of 14CO2 production with (aminooxy)acetic acid but not with glutamic acid diethyl ester indicated that transamination but not oxidative deamination of glutamate plays a major role in glutamate oxidation during normal and hyperammonemic states.
Mol Chem Neuropathol 1993 Aug
PMID:Transport and metabolism of glutamate by rat cerebellar mitochondria during ammonia toxicity. 810 3


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