Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of aminooxyacetic acid (AOAA), a transaminase inhibitor, and 2-oxoglutarate, a precursor to glutamate by the activity of aspartate aminotransferase (AAT), on slices of rat medulla oblongata, cerebellum, cerebral cortex, and hippocampus were studied. The slices were superfused and electrically stimulated. There was a Ca2+-dependent stimulus-evoked release of endogenous glutamate, gamma-aminobutyric acid (GABA), and beta-alanine in all regions examined. AOAA (10(-4) and 10(-3) M) decreased the release of glutamate in the medulla oblongata and cerebellum but not in the hippocampus. L-Canaline, a specific inhibitor of ornithine aminotransferase, did not affect the glutamate release in the medulla. 2-Oxoglutarate (10(-3) M) increased the release of glutamate in the medulla oblongata and cerebellum but not in the cerebral cortex and hippocampus. Treatment with AOAA (10(-4) M) almost abolished the activities of AAT in all regions studied. AOAA (10(-4) and 10(-3) M) increased the stimulus-evoked release of GABA in the cerebellum, cerebral cortex, and hippocampus, whereas the stimulus-evoked release of beta-alanine was decreased by this agent in all regions studied. These results suggest the participation of AAT in the synthesis of the transmitter glutamate in the medulla oblongata and cerebellum of the rat.
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PMID:Aspartate aminotransferase for synthesis of transmitter glutamate in the medulla oblongata: effect of aminooxyacetic acid and 2-oxoglutarate. 256 22

Of many glutamatergic parameters studied in human Huntington's disease, the following abnormalities were documented in the literature: Decreased glutamate content in cerebrospinal fluid and frontal cortex. Decreased activities of glutamine synthetase, ornithine aminotransferase and aspartate aminotransferase in various brain regions, especially the frontal cortex, caudate nucleus and putamen. Decreased glutamate binding in fibroblast membranes. Although it has been hypothesized that Huntington's disease may have a glutamate-related etiology, presently available evidence is too fragmented and inadequate for any conclusion to be made. However, it is noted that interpretation of these human data is very difficult because of two reasons. Firstly, changes observed in postmortem Huntington's disease brains may only be secondary to the disease instead of being the cause of the disease. Secondly, there is always doubts as to the relevance of data obtained with non-neural tissues such as fibroblasts and platelets.
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PMID:Abnormalities in glutamatergic mechanisms in human Huntington's disease. 298 4

The nucleotide sequence of ornithine aminotransferase mRNA from rat liver, including the entire coding and 3' untranslated regions, was determined from two overlapping cDNA clones. The mRNA encodes a precursor polypeptide of 439 amino acid residues with a molecular weight of 48,332. The deduced amino acid composition of the proposed mature enzyme sequence (residues 35 through 439) was in good agreement with that reported for the purified protein. The amino-terminal segment of the precursor corresponding to residues 1 through 34 has an overall positive charge, containing 6 basic residues and only a single acidic residue, and is postulated to be the mitochondrial leader sequence. The first 22 amino acid residues of the proposed leader sequences share 54% homology with the leader peptide of rat ornithine transcarbamylase precursor and more limited homology to the leader peptides of other nuclear-encoded mitochondrial matrix proteins. Homology was also observed between residues 286 through 362 ornithine aminotransferase precursor and a region containing the pyridoxyl phosphate binding domain of mitochondrial aspartate aminotransferase.
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PMID:Sequence of the precursor to rat ornithine aminotransferase deduced from a cDNA clone. 384 Apr 76

Livers of rats between the 16th gestational and 100th postnatal day of age were subjected to quantitative biochemical and electron microscope, morphometric analyses. The amount of total mitochondrial protein per gram of liver remained at 34% of the adult level throughout the last 4 days of gestation but this was the period of rapid rise in the levels of cytochrome c oxidase, aspartate aminotransferase, and glutamate dehydrogenase in mitochondria; the nuclear fraction also acquired some glutamate dehydrogenase but lost most of it during postnatal development. During early postnatal life the amount of mitochondrial protein rose in parallel with the levels of cytochrome c oxidase and glutamate dehydrogenase but the upsurges of glutaminase and, later, of ornithine aminotransferase were accompanied by relatively little change in total mitochondrial protein. The surface area of rough endoplasmic reticulum per unit volume of hepatocyte cytoplasm (S(v) (RER)) did not change significantly throughout the period of development studied. From the 16th day of gestation to term the surface area of smooth ER (S(v) (SER)), the volume occupied by mitochondria (V(v) (MT)) and their number (N(v) (MT)) remained at 30, 66, and 45% of their adult values, respectively. V(v) (MT) and N(v) (MT) attained their maximal levels by the 2nd postnatal day and S(v) (SER) between days 2 and 12. Mitochondria of adult liver are thus smaller and contain more protein per unit volume than do those of fetal liver. After the 12th postnatal day, hepatocytes treble their size; they acquire more cytoplasm with additional enzymes but without further change in organelle concentration. The data reveal several distinct phases in the differentiation of hepatocytes. Each phase can be characterized by the extent to which the quantity and composition of various subcellular compartments evolve.
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PMID:Subcellular morphometric and biochemical analysis of developing rat hepatocytes. 434 89

The effects of cortical lesions and intrastriatal kainic acid injections on various striatal enzyme activities were investigated. Ornithine aminotransferase decreased concomitantly with glutamate uptake in decorticated and chronic kainic acid-treated rats. It was also decreased in acute kainic acid-lesioned striatum where glutamate uptake was unaffected. Aspartate aminotransferase, however, decreased only after acute kainic acid treatment. Results for glutamate uptake, glutamate decarboxylase, and choline acetyltransferase were in agreement with previous findings. These results suggest that ornithine may act as a precursor for glutamate in nerve terminals, although the nonspecific localization does not allow ornithine aminotransferase to be a convenient biochemical marker. The decrease in aspartate aminotransferase is thought to be due to the widespread cell degeneration after acute kainic acid. Aspartate aminotransferase activities were also found to be reduced in the frontal cortex, caudate nucleus and putamen of Huntington's disease brains.
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PMID:Effects of kainic acid injection and cortical lesion on ornithine and aspartate aminotransferases in rat striatum. 613 Nov 42

The extent of inactivation of three aminotransferases by the enzyme activated inhibitor 4-amino-hex-5-ynoate (acetylenic-GABA) increased with increasing dose in an exponential fashion. Theoretical treatment of the data allowed an estimate of the effective concentration of the drug at its site of action to be made and it was apparent that any rises in substrate concentration produced by the inactivation did not protect the enzyme significantly. Altered diet produced distinct changes in the extent of inactivation of aspartate aminotransferase, but not with ornithine aminotransferase. Cysteine sulphinate, a substrate only of aspartate aminotransferase, also affected the inactivation of ornithine aminotransferase, suggesting that secondary metabolic effects were responsible.
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PMID:A kinetic model for the action of the enzyme activated irreversible inhibitor 4-amino-5-hexynoic acid in vivo. 650 32

beta-Methylene-DL-aspartate, a new beta, gamma-unsaturated amino acid, is an irreversible inhibitor of soluble pig heart glutamate-aspartate transaminase (Ki approximately 3 mM with respect to the L-form; limiting rate constant for inactivation approximately 0.4 min-1). The new amino acid is the most specific inhibitor of glutamate-aspartate transaminase thus far studied. It does not inactivate pig heart glutamate-alanine transaminase, soluble rat kidney glutamine transaminase K, gamma-aminobutyrate transaminase (from Pseudomonas fluorescens), glutamate decarboxylase (Escherichia coli), snake venom L-amino acid oxidase, or hog kidney D-amino acid oxidase. In addition, the following enzymes were not inhibited by beta-methylene-DL-aspartate in rat tissue homogenates: gamma-aminobutyrate transaminase (brain), tyrosine transaminase (liver), glutamine transaminase L (liver), asparagine, transaminase (liver), ornithine transaminase (liver) or branch-chain transaminase(s) (kidney). Intraperitoneal injection of beta-methylene-DL-aspartate into mice decreased kidney and liver glutamate-aspartate transaminase activities but had no effect on liver glutamate-alanine transaminase activity.
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PMID:Inhibition of glutamate-aspartate transaminase by beta-methylene-DL-aspartate. 683 Jun 31

Ornithine aminotransferase is shown to bind 1 mol of amino[14C]hexynoate per mol of coenzyme in the 'suicide' inactivation process. At the same time the coenzyme pyridoxal phosphate becomes irreversibly bound to the enzyme protein. Apart from the inactivation, the labelled enzyme is indistinguishable from native ornithine aminotransferase by several separation techniques. Because the rate of degradation of the labelled enzyme is the same as that of the normal enzyme it is concluded that loss of coenzyme does not initiate turnover. Free aminohexynoate is rapidly eliminated from the liver, and 70% of the compound is excreted unchanged in 7.5 h. Inactivated ornithine aminotransferase accounts for 11% of the total labelled liver protein and significant amounts of label are found in aspartate aminotransferase which is also extensively inactivated. The rate of return of enzyme activity is determined and found to be more rapid than expected for a process in which the enzyme is synthesized at a constant rate and degraded in a single, first-order process.
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PMID:An investigation of the properties of ornithine aminotransferase after inactivation by the 'suicide' inhibitor aminohexynoate and use of the compound as a probe of intracellullar protein turnover. 684 11

Glutamate is believed to be an excitatory amino acid neurotransmitter in the retina. Enzymes for glutamate metabolism, such as glutamate dehydrogenase, ornithine aminotransferase, glutaminase, and aspartate aminotransferase (AAT), exist mainly in the mitochondria. The abnormal increase of intracellular calcium ions in ischemic retinal cells may cause an influx of calcium ions into the mitochondria, subsequently affecting various mitochondrial enzyme activities through the activity of mitochondrial calpain. As AAT has the highest level of activity among enzymes involved in glutamate metabolism, we investigated the change of AAT activity in ischemic and hypoxic rat retinas and the protection against such activity by calpain inhibitors. We used normal RCS (rdy+/rdy+) rats. For the in vivo studies, we clamped the optic nerve of anesthetized rats to induce ischemia. In the in vitro studies, the eye cups were incubated with Locke's solution saturated with 95% N2/5% CO2. The activity of cytosolic AAT (cAAT) was about 20% of total activity, whereas mitochondrial AAT (mAAT) was about 75% in rat retina. Ninety minutes of ischemia or hypoxia caused a 20% decrease in mAAT activity, whereas cAAT activity remained unchanged. To examine the contribution of intracellular calcium ions to the degradation of mAAT, we used Ca2+-free Locke's solution containing 1 mM EGTA, ryanodine (Ca2+ channel blocker), and thapsigargin (Ca2+-ATPase inhibitor). In the present study, thapsigargin in Ca2+-free Locke's solution, but not ryanodine in this solution, was found to prevent AAT degradation. AAT degradation was also prevented by calpain inhibitors (Ca2+-dependent protease inhibitor) such as calpeptin at 1 nM, 10 nM, 0.1 microM, 1 microM and 10 microM, and by calpain inhibitor peptide, but not by other protease inhibitors (10 microM leupeptin, pepstatin, chymostatin). Additionally, we determined the subcellular localization of calpain activity and examined the change of calpain activity in ischemic rat retinas. Our results suggest that decreased activity of mAAT in ischemic and hypoxic rat retinas might be evoked by the degradation by calpain-catalyzed proteolysis in mitochondria.
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PMID:Possible mechanism for the decrease of mitochondrial aspartate aminotransferase activity in ischemic and hypoxic rat retinas. 1039 49

The mechanism of pellagrous changes in skin caused by a deficiency of vitamin B6 was studied in respect to neogenesis of proline in skin collagen and glucose metabolism. In vitamin B6 deficiency the insulin/glucagon coefficient in serum decreased significantly from 3.02 to 2.32, indicating a metabolic change towards gluconeogenesis. A deficiency of vitamin B6 caused a decrease in the levels of vitamin B6-dependent enzymes, such as ornithine aminotransferase, alanine aminotransferase, and aspartate aminotransferase, which also contribute to gluconeogenesis. Because the conversion of ornithine to proline via pyrroline-5-carboxylate was suppressed due to the decrease in ornithine aminotransferase activity, the amount of proline in the skin collagen fraction also decreased significantly in vitamin B6-deficient rats compared with the pair-fed control. These results suggest that the pellagrous lesions in vitamin B6-deficiency are caused by an impaired synthesis of proline from ornithine, which results in the suppression of collagen neogenesis in the skin.
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PMID:Changes of glucose metabolism and skin-collagen neogenesis in vitamin B6 deficiency. 1617 47


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