Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Target Concepts:
Gene/Protein
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Enzyme
Compound
Query: EC:2.6.1.2 (
alanine aminotransferase
)
26,722
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
New biologically active compounds (BAC) created on the basis of nicotinic acid possess hepatoprotective action. The preparations were introduced preventively in doses of 10 mg/kg during 14 days. Litonit and nicogamol increased survival of experimental animals by 36.8% and nicotinic acid by 26.8%.
ALT
, AST, GGT activity in the blood serum was reduced. The activity of the main antioxidant enzymes (
SOD
and catalase) grew in the rat liver tissue in parallel with inhibition of DK and MDA activity. Morphological picture of the rat liver, most evident after application of litonit improved. Hepatoprotective action of these BAC are attributed to their membrano stabilizing effects.
...
PMID:[Mechanisms of hepatoprotective action of new nicotinic acid derivatives in experimental CCL4-induced liver injury]. 142 11
Serum Mn-superoxide dismutase (Mn-SOD) was determined in patients with various liver diseases including 31 patients with primary biliary cirrhosis (PBC), 46 with hepatocellular carcinoma (HCC), 17 with liver cirrhosis (LC), 23 with chronic hepatitis (CH) and 12 patients with obstructive jaundice with an enzyme-linked immunosorbent assay using a specific monoclonal antibody. The serum level in patients with PBC (407 +/- 35 ng/ml, mean +/- SEM; n = 31) was significantly increased (p less than 0.01) compared with those of other liver diseases. Mn-
SOD
level did not correlate with total bilirubin level, gamma-glutamyl transpeptidase activity, alkaline phosphatase activity,
alanine aminotransferase
activity, IgM, or with ceruloplasmin level in the sera of the patients. When the patients with PBC were histologically subdivided into four groups according to Scheuer's classification (Scheuer PJ. Primary biliary cirrhosis. In: Scheuer PJ, ed. Liver biopsy interpretation. 3rd ed. London: Bailliere Tindall, 1980:47-56), a high level of serum Mn-
SOD
was noticed in the early stage as well as in the advanced stage of the disease. Immunoblot analysis confirmed the reactivity and specificity of the monoclonal antibody to the enzyme protein in the patients' sera. Immunostaining of a liver biopsy specimen from the patients with PBC revealed increased expression of the enzyme protein in damaged epithelial cells of interlobular bile ducts, bile ductules, and degenerated hepatocytes. These data suggested that free radicals including superoxide anion are possibly involved in the pathogenesis of the disease and Mn-
SOD
may play some role in a protection against the superoxide anion.
...
PMID:Elevated level of serum Mn-superoxide dismutase in patients with primary biliary cirrhosis: possible involvement of free radicals in the pathogenesis in primary biliary cirrhosis. 168 6
The susceptibility to lipid peroxidation (LPO) of liver, kidneys, brains, lungs, heart, and testes was assessed in rats administered intraperitoneally with various doses of cadmium (Cd). Dose-response studies were carried out with male Long Evans rats (12-week-old; 300 +/- 33 g) injected with 25, 125, 500, and 1250 micrograms Cd/kg as CdCl2 and sacrificed after 24 h. In time-response studies, animals were administered with 25 and 500 micrograms Cd/kg as CdCl2 and sacrificed after 2, 6, 12, 24, and 72 h. Exposure of rats to low and moderate doses of Cd by the intraperitoneal route stimulated LPO in all the tissues investigated as assessed by the measurement of thiobarbituric acid reactive substances (TBARS). Lungs and brain were the most responsive, and these tissues and liver displayed early responses following Cd exposure. Comparison of LPO to various tissue indicators (for liver:
alanine aminotransferase
(
ALT
), sorbitol dehydrogenase (SDH), alkaline phosphatase (ALP); for lungs: ALP, gamma-glutamyl transpeptidase (GGT] suggested that low doses of Cd stimulated LPO without any evidence of acute damages. These results suggest that LPO is an early and sensitive consequence of Cd exposure as determined in various organs. Investigation of liver, lungs, and heart antioxidant defense system components (glutathione peroxidase (GPX), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PDH), superoxide dismutase (
SOD
] revealed that GPX might be considered as a potential modulator of the Cd-induced LPO reaction in lungs and heart tissues.
...
PMID:Studies on lipid peroxidation in rat tissues following administration of low and moderate doses of cadmium chloride. 182 34
The complete amino acid sequence of human liver cytosolic
alanine aminotransferase
(
GPT
) (
EC 2.6.1.2
) is presented. Two primary sets of overlapping fragments were obtained by cleavage of the pyridylethylated protein at methionyl and lysyl bonds with cyanogen bromide and Achromobacter protease I, respectively. Isolated peptides were analyzed with a protein sequencer or with a plasma desorption time of flight mass spectrometer and placed in the sequence on the basis of their molecular mass and homology to the sequence of rat
GPT
. The protein was found to be acetylated at the amino terminus and contained 495 amino acid residues. The Mr of the subunit was calculated to be 54,479, which was in good agreement with a Mr of 55,000 estimated by SDS-PAGE, and also indicated that the active enzyme with a Mr of 114,000 was a
homodimer
composed of two identical subunits. The amino acid sequence is highly homologous to that of rat
GPT
(87.9% identity) recently determined [Ishiguro, M., Suzuki, M., Takio, K., Matsuzawa, T., & Titani, K. (1991) Biochemistry 30, 6048-6053]. All of the crucial amino acid residues are conserved in human
GPT
, which seem to be hydrogen bonding to pyridoxal 5'-phosphate in rat
GPT
by the sequence homology to other alpha-aminotransferases with known tertiary structures.
...
PMID:Complete amino acid sequence of human liver cytosolic alanine aminotransferase (GPT) determined by a combination of conventional and mass spectral methods. 193 70
Hepatotoxicity of diethyldithiocarbamate (DDC) was investigated in rats. Plasma aspartate aminotransferase (AST) and
alanine aminotransferase
(
ALT
) activities were markedly elevated 24 hr after subcutaneous administration of DDC and histologically, the liver showed submassive necrosis. A sustained inhibition in the liver of Cu,Zn-superoxide dismutase (Cu-SOD) activity was observed following DDC treatment. DDC produced a significant loss in liver reduced glutathione (GSH) level after 1 hr, but the nadir was observed later than that of Cu-
SOD
. Catalase activity decreased gradually from 7 hr. Thiobarbituric acid reactive substances (TBARS) in the liver were significantly increased from 15 hr. Hepatic haemodynamics were scarcely changed up to 15 hr. Desferrioxamine (a chelator of iron) and piperonyl butoxide (an inhibitor of cytochrome P-450) prevented DDC-induced increases of both
ALT
and TBARS, but GSH did not, DDC hepatotoxicity was not changed by phenobarbital induction. Thus, we have shown that subcutaneous dose of DDC caused hepatotoxicity in rats. Although the exact sequence of its hepatotoxic factors is unproven, it seems likely that lipid peroxidation through the dysfunction of antioxidant defence factors and a toxic metabolite contribute to the formation of this liver injury.
...
PMID:Hepatotoxicity of diethyldithiocarbamate in rats. 196 45
The complete amino acid sequence of rat liver cytosolic
alanine aminotransferase
(
EC 2.6.1.2
) is presented. Two primary sets of overlapping fragments were obtained by cleavage of the pyridylethylated protein at methionyl and lysyl bonds with cyanogen bromide and Achromobacter protease I, respectively. The protein was found to be acetylated at the amino terminus and contained 495 amino acid residues. The molecular weight of the subunit was calculated to be 55,018 which was in good agreement with a molecular weight of 55,000 determined by SDS-PAGE and also indicated that the active enzyme with a molecular weight of 114,000 was a
homodimer
composed of two identical subunits. No highly homologous sequence was found in protein sequence databases except for a 20-residue sequence around the pyridoxal 5'-phosphate binding site of the pig heart enzyme [Tanase, S., Kojima, H., & Morino, Y. (1979) Biochemistry 18, 3002-3007], which was almost identical with that of residues 303-322 of the rat liver enzyme. In spite of rather low homology scores, rat
alanine aminotransferase
is clearly homologous to those of other aminotransferases from the same species, e.g., cytosolic tyrosine aminotransferase (24.7% identity), cytosolic aspartate aminotransferase (17.0%), and mitochondrial aspartate aminotransferase (16.0%). Most of the crucial amino acid residues hydrogen-bonding to pyridoxal 5'-phosphate identified in aspartate aminotransferase by X-ray crystallography are conserved in
alanine aminotransferase
. This suggests that the topology of secondary structures characteristic in the large domain of other alpha-aminotransferases with known tertiary structure may also be conserved in
alanine aminotransferase
.
...
PMID:Complete amino acid sequence of rat liver cytosolic alanine aminotransferase. 204 42
In the present paper we report on new data of the frequency of common and rare variants in the Italian population for ADA, AK-1, 6-PGD, EsA, EsB, EsD, PGM-1, PGM-2,
SOD
-A, AcP,
GPT
, and PGI. Moreover we present a comprehensive review of the available data on the electrophoretic variants of red cell enzymes in Italians. We find a considerable degree of genetic heterogeneity between the various populations living in the Peninsula and between the population of the Peninsula and of Sardinia. We also find that the estimates of the average heterozygosity are considerably smaller for the population of Sardinia as compared to Peninsula and Sicily. Finally, we report on the occurrence of several uncommon enzyme variants, which overall frequency is very similar to previously reported estimates for North European populations (Harris et al. 1974).
...
PMID:Common and rare genetic variants of human red blood cell enzymes in Italy. 252 24
A sample of 465 persons from Eastern Sicily was studied for 11 red-cell enzymes, namely GLO,
GPT
, EsD, PGP, PGD, Dia, AcP, PGM,
SOD
, CAI and CAII. The allele frequencies were compared with those of other Italian populations and showed that the island is homogeneous with the mainland for these systems. The rate of heterozygosity was studied as a function of interparental distance; although high (0.77) the correlation did not reach significance.
...
PMID:Population structure of eastern Sicily. 302 78
The gene frequencies at eight loci in some European and Asian human populations have been subjected to spatial autocorrelation analysis, using Geary's c coefficient. Contrary to what is expected for markers affected only by gene flow and genetic drift, the spatial correlograms show distinct modes of gene frequency variation: there are significant clinal patterns (at the GLO and ESD loci), significant non-clinal patterns (AK, ADA, 6-PGD and
GPT
) and marginally significant patterns (PGP and
SOD
). Any hypothesis on the evolution of these polymorphisms should account for the observed heterogeneity of their geographical distributions.
...
PMID:Diversity of some gene frequencies in European and Asian populations. III. Spatial correlogram analysis. 348 48
Allele frequencies are reported for 19 blood group, red cell enzyme, and serum protein loci (ABO, Rh, MN, Hb-A, LDH-A, LDH-B,
SOD
, PGM-1, PGM-2, 6PGD,
GPT
, ESD, ADA, ACP, PGK, MDH, Alb, Hp, and Tf) determined from 310 blood samples collected among the Gainj, a small population of tribal horticulturalists from highland Papua New Guniea. Fourteen of these loci display genetic variants, and ten of them are sufficiently polymorphic to permit a preliminary analysis of Gainj population structure. Patterns of variation among subdivisions of the population are analyzed using an approach analogous to a multivariate analysis of variance with unbalanced design, and weighted genetic distances are extracted from the results. The distance analysis indicates that patterns of genetic variation within this population reflect the geographical distribution of subdivisions, as well as subdivision size and movement among subdivisions. A parallel analysis of the Gainj and two other tribal groups from highland New Guinea, the Murapin Enga and the Simbai Valley Maring, suggests that the Gainj are both genetically divergent from neighboring populations and internally highly differentiated.
...
PMID:The genetic demography of the Gainj of Papua New Guinea. I. Local differentiation of blood group, red cell enzyme, and serum protein allele frequencies. 713 24
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