Disease relevance of Got1

• A detailed analysis of cAspAT promoter activity revealed that the mechanism of regulation by GR in Schwann cells differs from that in hepatoma cells, suggesting a cell-specific regulation [1].
• Acute toxicity developed within the first 10 days and was expressed by a depressed hematocrit and elevated plasma levels of glutamate-pyruvate transaminase, glutamate-oxaloacetate transaminase, lactic dehydrogenase, amylase, lipase, and uric acid [2].
• This hybrid protein represented about 18% of the soluble proteins in E. coli and its kinetic properties were comparable with those of cAspAT preparations purified from rat liver [3].
• Glutamate oxaloacetate transaminase (GOT) in the dy2J genotypes of C57BL/6J mice: possible involvement of regulatory defect in muscular dystrophy [4].
• Structural organization of the human cytosolic aspartate aminotransferase gene was determined by analyzing the phage clones obtained from two kinds of genomic DNA libraries, using mouse cytosolic aspartate aminotransferase cDNA as a probe [5].

High impact information on Got1

• Chromosomal deletions around the albino locus in the mouse cause loss of hormone-inducible expression of the unlinked structural gene encoding cytosolic aspartate aminotransferase [6].
• The results reported here identify an additional unlinked structural gene whose regulation appears to be affected by the deletions--i.e., that encoding cytosolic aspartate aminotransferase, a housekeeping gene that participates in gluconeogenesis in the liver [6].
• Finally, about 7 weeks after treatment, a terminal phase indicated by correlated increases in glutamate-pyruvate transaminase, glutamate-oxaloacetate transaminase, lactic dehydrogenase, and blood urea nitrogen became apparent [2].
• The malate-aspartate shuttle, consisting of mitochondrial and cytosolic aspartate aminotransferase and mitochondrial and cytosolic malate dehydrogenase, is a major pathway for the transport of reducing equivalents from cytosol to mitochondria in mammals [7].
• The region coding for the mature mAspAT and that for the cAspAT show about 53% overall homology [8].

Chemical compound and disease context of Got1

• Several toxicity biomarkers such as acid and alkaline phosphatases, glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and lipid peroxidation activity were also assayed in three organs of treated and control mice [9].
• An increased activity of alkaline phosphatase, glutamate-pyruvate and glutamate-oxaloacetate transaminase was observed in liver with cimetidine administration, whereas that of lactate and succinate dehydrogenase was inhibited only after administration of 2000 mg cimetidine per kg body weight [10].

Biological context of Got1

• The transactivation potency of the two Glucocorticoid Responsive Units (GRU) present in the cAspAT promoter seems to be dependent on the levels of the GR in MSC80 cells [1].
• The gene order Ly-1 - Got-1 - 4.7 +/- 1.6 - Es-18 is suggested [11].
• The deduced amino acid sequence of the mouse cAspAT shares 91% homology with that of the pig cAspAT [8].
• The nucleotide sequences of mRNAs for the mouse mitochondrial and cytosolic aspartate aminotransferase isoenzymes (mAspAT and cAspAT) (EC 2.6.1.1) were determined from complementary DNAs [8].
• The hypothesis that a part of LG II (e-Es) shares homologies with mouse chromosome 8 is thus confirmed, as the murine homologue of GOTM is located within the cluster of esterase loci on chromosome 8 [12].

Anatomical context of Got1

• Three previously described electrophoretic phenotypes of mitochondrial glutamate oxaloacetate transaminase (GOTM) in horse leukocytes are shown to be controlled by two codominant alleles at a single autosomal locus [12].
• Assignment of the gene for cytoplasmic glutamate-oxaloacetate transaminase to mouse chromosome 19 using chinese hamster x mouse somatic cell hybrids [13].
• We demonstrate that these stimuli induce the expression of the cytosolic aspartate aminotransferase gene in adipocytes by a process involving the region of the promoter between -2405 and -26 bp [14].
• The release of glutamate-oxaloacetate transaminase by hepatocytes was not affected by the indoles, although the release of glutamate-pyruvate transaminase was increased to a small extent and the uptake of crystal violet was slightly inhibited [15].
• However, the glutamate oxaloacetate transaminase and glutamate pyruvate transaminase activities of the three astroglial cell lines, measured in the direction of glutamate synthesis, were comparable [16].

Associations of Got1 with chemical compounds

• Chinese hamster and mouse cytoplasmic glutamate-oxaloacetate transaminase (GOT-1, EC 2.6.1.1) were separated by isoelectric focusing of cell extracts on thin-layer polyacrylamide plates [13].
• L-Cysteinesulfinate, a quantitatively important catabolite of L-cysteine, is a substrate of both cysteinesulfinate decarboxylase and glutamate-oxaloacetate transaminase [17].
• Cytosolic aspartate aminotransferase gene is a member of the glucose-regulated protein gene family in adipocytes [14].
• The hepatotoxicity of paracetamol in mice of 2, 3, 8-10, 24-26, 32-34, and 52-54 wk of age was determined by lethality data, histopathologic examination of the liver, and appearance of glutamate-pyruvate transaminase and glutamate-oxaloacetate transaminase activities in the plasma over an 8-h exposure period [18].
• When administered at selected times immediately following removal of medium containing 10 mM APAP, 2.0 mM NAC was shown to restore glutathione levels through 16 hr of APAP pretreatment and to minimize the leakage of glutamate-oxaloacetate transaminase resulting from the first 8 hr of drug exposure [19].
• RORalpha ectopic expression activated the cAspAT gene transcription in absence of rosiglitazone, and its protein amount in nuclear extracts is 1.8-fold increased by rosiglitazone treatment of adipocytes [20].

Other interactions of Got1

• The GOTM locus is linked to the serum esterase locus (Es), as no recombination between these loci was observed among 16 informative offspring in one sire family [12].
• This extract has been shown to possess significant protective effect by lowering serum transaminase levels (serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase), alkaline phosphatase and bilirubin [21].
• In conclusion, fenofibrate has been shown to modify cAspAT and AlaAT gene expression in a species and PPARalpha dependent manner [22].
• The activities of glutamate oxaloacetate transaminase-1 and phosphoglycerate mutase-1 are increased by 50%, compatible with a gene dosage effect of these two enzymes [23].
• The increased serum enzyme levels (viz., glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, lactate dehydrogenase, alkaline phosphatase, sorbitol and glutamate dehydrogenase) by CCl4-induction were significantly lowered due to pretreatment with the extract [24].

Analytical, diagnostic and therapeutic context of Got1

• It has been observed that adrenalectomy decreases and hydrocortisone treatment to adrenalectomized mice increases the activity of cytosolic and mitochondrial malate dehydrogenase and cytosolic aspartate aminotransferase in the liver of 15-, 30- and 60-day old mice [25].

References