Disease relevance of Got1

• Rat cytosolic aspartate aminotransferase: molecular cloning of cDNA and expression in Escherichia coli [1].
• The regulation of cytosolic aspartate aminotransferase (cAspAT) gene expression by phorbol esters was investigated in the highly differentiated hepatoma cell line Fao [2].
• Development of deficiencies was monitored by growth rate, food intake, ratio of liver weight to body weight and the biochemical parameters (thiamin diphosphate effects for thiamin deficiency, glutathione reductase activity coefficient for riboflavin deficiency and erythrocyte glutamate-oxaloacetate transaminase activity for pyridoxine deficiency) [3].
• Thiamin deficiency slightly increased the acute toxicity of dimethylnitrosamine as observed by the lowering of the LD50 dose and the greater increase in the serum glutamate-oxaloacetate transaminase and serum glutamate-pyruvate transaminase levels [3].
• ACE inhibition by captopril reverted the L-NAME-induced hypertrophy and inhibited the enzymatic indices of cardiac damage (glutamate oxaloacetate transaminase and lactate dehydrogenase) back to normal values [4].

High impact information on Got1

• Contribution of a nuclear factor 1 binding site to the glucocorticoid regulation of the cytosolic aspartate aminotransferase gene promoter [5].
• The cytosolic aspartate aminotransferase activity was 5-fold lower in the testis than in the liver and kidney [6].
• The promoter of the gene coding for the rat cytosolic aspartate aminotransferase was cloned from a Charon 4A genomic library [7].
• The 1.8-kb and the 2.1-kb cytosolic aspartate aminotransferase mRNAs differ in their 3' ends and probably result from the use of either of the two polyadenylation signals present in the 3' noncoding region of the major cytosolic aspartate aminotransferase mRNA [8].
• Enzymes with long half-lives in plasma, namely lactate dehydrogenase H4, alanine aminotransferase, and cytosolic aspartate aminotransferase did not compete at concentrations up to 10 microM [9].

Chemical compound and disease context of Got1

• Regulation of cytosolic aspartate aminotransferase mRNAs in the Fao rat hepatoma cell line by dexamethasone, insulin and cyclic AMP [10].
• Rats injected with a single dose of cyclophosphamide (200 mg kg-1 body weight) showed an increase in the levels of serum glutamate-oxaloacetate transaminase, serum glutamate-pyruvate transaminase, glucose-6-phosphate dehydrogenase and creatine phosphokinase isoenzyme by 53, 24, 55 and 135%, respectively [11].
• A single dose of adriamycin (10 mg/kg body weight) caused myocardial damage that was manifested by elevation of serum enzymes, glutamate-oxaloacetate transaminase (GOT), glutamate-pyruvate transaminase (GPT), lactate dehydrogenase isoenzyme (LDH-iso) and creatine phosphokinase isoenzyme (CPK2-MB) [12].
• Oral application of lindane at a dose of 2 mg/100 g body weight of rat/day for 15 days produced alterations in the activities of several enzymes viz, glutamate oxaloacetate transaminase, alkaline phosphatase, acetylcholinesterase and inorganic pyrophosphatase in different organs and serum [13].

Biological context of Got1

• Cytosolic aspartate aminotransferase (cAspAT) participates in gluconeogenesis in the liver and is expected to exert a glyceroneogenic function in the adipose tissue when the supply of glucose is limited [14].
• The CCl4 injection significantly increased the indicators of hepatic function (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase), but not of renal function (blood urea nitrogen, glomerular filtration rate) [15].
• The cells were cultured for 22 h without loss of protein synthesis capability or significant changes in cell count, viability, endogenous glutamate-oxaloacetate transaminase (GOT) or Fe and were morphologically similar in most respects to unloaded (normal) hepatocytes similarly cultured [16].
• Evidence based on substrate specificity, enzyme inhibition, and physicochemical properties indicates that cytosolic cysteine aminotransferase is identical with cytosolic aspartate aminotransferase (L-aspartate: 2-oxoglutarate aminotransferase, EC 2.6.1.1) [17].

Anatomical context of Got1

• Inhibition by cycloserine of mitochondrial and cytosolic aspartate aminotransferase in isolated rat hepatocytes [18].
• Furthermore, the transport of glycolytic hydrogen, produced by the glyceraldehyde 3-phosphate dehydrogenase-catalyzed reaction, from the cytosol into the mitochondria by means of the malate-aspartate shuttle was enhanced, this being due to alterations in the activities of malate dehydrogenase and glutamate oxaloacetate transaminase [19].
• This study was conducted to determine the ultrastructural localization of cytosolic aspartate aminotransferase (cAAT)-like immunoreactivity in the cerebellar cortex in the rat [20].
• These facts suggest that aspartate could intervene as a co-neurotransmitter or neuromodulator in the rat cochlear nucleus, and that axonic endings could contain cAATase, GABA and GAD [21].
• Ultrahistochemical localization of the glutamate-oxaloacetate transaminase (GOT) enzyme in hepatic and skeletal muscle cells in rat [22].

Associations of Got1 with chemical compounds

• Administration of dexamethasone, which induces the synthesis of tyrosine aminotransferase and cytosolic aspartate aminotransferase, selectively increased the sequestration of these enzymes to proportional degrees [23].
• Cytosolic aspartate aminotransferase, in contrast, adsorbs weakly to the hydroxylapatite column and transaminates tyrosine very poorly although it readily utilizes monoiodotyrosine [24].
• Over a 30-fold increase in glutamate concentration, the flux through the glutamate-oxaloacetate transaminase increased 7--8-fold, whereas the flux through 2-oxoglutarate dehydrogenase increased about 2.5-fold [25].
• Identification of an adipocyte-specific negative glucose response region in the cytosolic aspartate aminotransferase gene [14].
• 5. The intramitochondrial concentration of 2-oxoglutarate appears to be an important controlling parameter in the rate of 4-aminobutyrate metabolism, since, although 2-oxoglutarate is required, high concentrations (2.5 mM) of extramitochondrial 2-oxoglutarate inhibit the formation of aspartate via the glutamate-oxaloacetate transaminase [26].

Other interactions of Got1

• 1. The apparent Michaelis constants of the glutamate dehydrogenase (EC 1.4.1.3), the glutamate-oxaloacetate transaminase (EC 2.6.1.1) and the glutaminase (EC 3.5.1.2) of rat brain mitochondria derived from non-synaptic (M) and synaptic (SM2) sources were studied [25].
• The opposite was seen for glutamate decarboxylase, glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase, glutamate dehydrogenase, 2-ketoglutarate dehydrogenase and FAD-glycerophosphate dehydrogenase (m-GDH) [27].
• Induction of cytosolic aspartate aminotransferase by glucagon in primary cultured rat hepatocytes [28].
• It was suggested that increase of glucocorticoid receptor might result in increased synthesis of cytosolic aspartate aminotransferase in pyridoxine-deficient rat liver [29].
• In fact, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, glutamate-pyruvate-transaminase and glutamate-oxaloacetate-transaminase are lower, while citrate synthase, cytochrome oxidase and glutamate dehydrogenase are higher in intra-synaptic mitochondria than in non-synaptic ones [30].

Analytical, diagnostic and therapeutic context of Got1

• In contrast, cytosolic aspartate aminotransferase did not appear in the perfusate at slow rates of liver perfusion or during hypothermic perfusion [31].
• Cytosolic aspartate aminotransferase from rat liver was separated into at least 3 subforms, focused at pH 6.2, 5.9, and 5.7, by isoelectric focusing [32].
• The serum glutamate oxaloacetate transaminase levels at 24 hr after reperfusion were also lower in group 1 (320 +/- 22.2 IU/L) than in either group 2 or group 3 [33].
• Glycated cytosolic aspartate aminotransferase was detected in the liver and kidney of streptozotocin diabetic rats using a boronate affinity column for adjacent cis-hydroxyl groups and an immunoblotting technique [34].
• The oral administration of the extract (250 and 500 mg/kg) significantly reduced CCl(4) induced hepatotoxicity in rats, as judged from the serum and tissue activity of marker enzymes [glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP)] [35].

References