Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The conversion of cysteine to 3-sulfino-alanine is a major pathway in cysteine catabolism. Cysteine dioxygenase catalyzes the reaction and dietary intake of the essential amino acid methionine and the semi-essential amino acid cysteine increases the level of this enzyme by suppressing enzyme degradation via polyubiquitination. The production of cellular antioxidants such as glutathione, thioredoxin, and their families is important in cysteine metabolism, and these cellular antioxidants have critical roles in the maintenance of the cellular redox status. The mercaptopyruvate pathway, in which cysteine or aspartate transaminase catalyzes the transamination from cysteine to 3-mercaptopyruvate and then 3-mercaptopyruvate sulfurtransferase catalyzes the transsulfuration from 3-mercaptopyruvate to pyruvate, also contributes to maintain the cellular redox. 3-Mercaptopyruvate sulfurtransferase serves as an antioxidant protein: when the enzyme is exposed to stoichiometric amounts of the oxidant hydrogen peroxide, it is inhibited via the formation of low redox sulfenate at the catalytic site cysteine. On the other hand, activity is restored by the reductant dithiothreitol or reduced thioredoxin. 3-Mercaptopyruvate sulfurtransferase also detoxifies cyanide via transsulfuration from a stable persulfide at the catalytic site cysteine, a reaction intermediate, suggesting that cyanide detoxification is not necessarily an enzymatic reaction. Furthermore, a congenital defect of the enzyme causes mercaptolactate-cysteine disulfiduria associated with or without mental retardation, although the pathogenesis remains unclear. These facts suggest that 3-mercaptopyruvate sulfurtransferase has physiologic roles as an antioxidant and a cyanide antidote; is essential for neural function, and participates in cysteine degradation.
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PMID:The mercaptopyruvate pathway in cysteine catabolism: a physiologic role and related disease of the multifunctional 3-mercaptopyruvate sulfurtransferase. 1671 81

Hyperhomocysteinemia, a condition of elevated blood homocysteine level, is an independent risk factor for cardiovascular diseases. Hyperhomocysteinemia is also found in patients with liver diseases. However, the direct effect of homocysteine on liver injury is not well known. Folic acid supplementation is a promising approach for improving endothelial function in patients with hyperhomocysteinemia. The aim of this study was to investigate the direct effect of hyperhomocysteinemia on liver injury and whether folic acid could offer any protective effect to the liver. Hyperhomocysteinemia was induced in rats fed a high-methionine diet for 4 weeks. There was a significant increase in the serum aspartate aminotransferase and alanine aminotransferase activities reflecting liver injury in hyperhomocysteinemic rats. Hepatic NAD(P)H oxidase was activated during hyperhomocysteinemia leading to increased superoxide anion production and peroxynitrite formation in the liver. As a consequence, the level of lipid peroxides was significantly elevated in livers of hyperhomocysteinemic rats. Folic acid supplementation effectively inhibited NAD(P)H oxidase-mediated superoxide anion production leading to reduced lipid peroxidation in the liver. Folic acid supplementation also alleviated hyperhomocysteinemia-induced liver injury. These results suggest that hyperhomocysteinemia can cause liver injury and supplementation of folic acid offers a hepatoprotective effect.
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PMID:Hyperhomocysteinemia induces liver injury in rat: Protective effect of folic acid supplementation. 1683 72

Neurofibromatosis type 1 (NF1) is characterized by cafe-au-lait spots, skinfold freckling, and cutaneous neurofibromas. No obvious relationships between small mutations (<20 bp) of the NF1 gene and a specific phenotype have previously been demonstrated, which suggests that interaction with either unlinked modifying genes and/or the normal NF1 allele may be involved in the development of the particular clinical features associated with NF1. We identified 21 unrelated probands with NF1 (14 familial and 7 sporadic cases) who were all found to have the same c.2970-2972 delAAT (p.990delM) mutation but no cutaneous neurofibromas or clinically obvious plexiform neurofibromas. Molecular analysis identified the same 3-bp inframe deletion (c.2970-2972 delAAT) in exon 17 of the NF1 gene in all affected subjects. The Delta AAT mutation is predicted to result in the loss of one of two adjacent methionines (codon 991 or 992) ( Delta Met991), in conjunction with silent ACA-->ACG change of codon 990. These two methionine residues are located in a highly conserved region of neurofibromin and are expected, therefore, to have a functional role in the protein. Our data represent results from the first study to correlate a specific small mutation of the NF1 gene to the expression of a particular clinical phenotype. The biological mechanism that relates this specific mutation to the suppression of cutaneous neurofibroma development is unknown.
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PMID:An absence of cutaneous neurofibromas associated with a 3-bp inframe deletion in exon 17 of the NF1 gene (c.2970-2972 delAAT): evidence of a clinically significant NF1 genotype-phenotype correlation. 1716 Sep 1

Significant disorders of liver metabolic pathways enzymes after high-cholesterol diet could give information on liver steatosis development. This process could probably also be inhibited by some compounds, as examined in rabbits. Forty-two male rabbits were served a high-cholesterol diet (2 g%) (0.67 g/kg b.m./24 h) with addition of d,l-methionine (70 mg/kg b.m./24 h) or seleno-d,l-methionine (12.5 microg/kg b.m./24 h) or alpha-tocopherol (10 mg/kg b.m./24 h) for 3 months to compare the protection effect of used compounds on liver metabolism and steatosis. At the beginning and every month, blood was taken. After the experiment was completed, livers were dissected for histological examinations. The concentration of total cholesterol (t-CH), triacylglycerol (TG), and the activities of aldolase (ALD), sorbitol dehydrogenase (SDH), glutamate dehydrogenase (GLDH), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were determined. Plasma t-CH and TG concentrations were significantly higher in all experimental groups vs control group. Blood serum AST and ALT activities did not undergo change but there were observed not significant increase in the CH group vs control group. Activities of SDH, GLDH, and LDH increased in blood serum and decreased in the liver in all experimental groups. Activities of LDH and SDH increased in the liver in the CH+Met group vs CH group. ALD activity decreased in the liver only in the CH and CH+Se groups. This data support a lipotoxic model of cholesterol-mediated hepatic steatosis. Prolonged administration of high-cholesterol diet not only disturbs the structure of cell membranes, which is expressed by decreased activity of enzymes in the liver and the migration of those enzymes to plasma but as well leads to steatosis of the liver, which has been confirmed by histological examinations. The applied compounds appear to have a varying influence upon the activity of enzymes determined in serum and liver. Obtained results showed a beneficial influence of methionine and vitamin E supplementation on liver steatosis development.
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PMID:The influence of methionine, selenomethionine, and vitamin E on liver metabolic pathways and steatosis in high-cholesterol fed rabbits. 1791 70

To assess the effects of anti-TNF-alpha antibody (infliximab) in experimental steatohepatitis induced by methionine- and choline-deficient (MCD) diet. The study included thirty rats. One group received normal rat food, and two groups received MCD diet. The treatment group received a single dose intra-peritoneal infliximab (4 mg/kg), at week 8. MCD diet increased levels of AST, ALT, TNF-alpha, TGF-beta(1), tissue and plasma MDA (p < 0.05 for each). Moreover, it led to steatosis, ballooning degeneration, inflammation, fibrosis and increased actin expression, histopathologically (p < 0.05 for each). In this experimental steatohepatitis anti-TNF-alpha antibody decreased the levels of AST, ALT, TGF-beta(1) and plasma and tissue MDA (p < 0.05 for each). Moreover, inflammation, necrosis, actin expression and fibrosis decreased in anti-TNF-alpha group compared to placebo group (p < 0.05 for each). This study indicates that anti-TNF-alpha antibody is effective on necrosis, inflammation and fibrosis in the experimental model of non-alcoholic steatohepatitis, induced by MCD diet.
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PMID:The treatment with antibody of TNF-alpha reduces the inflammation, necrosis and fibrosis in the non-alcoholic steatohepatitis induced by methionine- and choline-deficient diet. 1806 56

The objective of the present study was to examine the effects of parenteral administration of iron and copper on hematological parameters, weight gain, and health of neonatal dairy calves in the period when iron and copper deficiency could be existed. Twenty-four Holstein calves were used for the experiment and randomly assigned to four different treatments. Treatments consisted of (1) control (no injections of Fe and Cu), (2) test 1 (1000 mg Fe as fe-dextran was injected to each calf at day 2 of age), (3) test 2 (160 mg Cu as methionine-copper complex was injected to each calf at day 14 of age), and (4) test 3 (Fe and Cu were injected to each calf as mentioned previously). Blood samples were collected from all of the calves within 24-48 hours after birth and at 7, 14, 21 and 28 days of age for measuring hematological parameters and within 24-48 hours after birth and at 14, 21 and 28 days of age for the determination of iron, copper, TIBC concentrations, and AST activity. Anti-coagulated blood was analyzed shortly after collection for: number of red blood cell (RBC), hemoglobin (Hb), heamatocrit (HCT), total leukocyte count (WBC), Platelet (Plt), MCH, MCV, MCHC, and differential leukocyte counts. The amounts of iron, copper, TIBC, and AST were measured in serum. Group had significant effects on the amounts of HCT, RBC, hemoglobin, MCV, neutrophil, weekly weight gain, and daily gain during each week (p < 0.05). Sampling time had significant effects on the amounts of RBC, MCV, MCH, MCHC, WBC, neutrophil, lymphocyte, monocyte, platelet, fibrinogen, copper, TIBC, AST, weight, weekly gain and, daily gain during each week (p < 0.05). significant interactions between sampling time and group were seen for HCT, RBC, hemoglobin, MCV, platelet, total protein, fibrinogen, iron, and TIBC (p < 0.05). Improved RBC parameters and MCV were seen in calves of group 4 (test 3) in comparing with control group. Total and daily gains were also significantly improved in test groups in comparing with control group (p < 0.05). No significant difference was seen for the days of treatment between groups.
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PMID:Effects of parenteral supply of iron and copper on hematology, weight gain, and health in neonatal dairy calves. 1847 51

The toxicological effects of realgar after intragastrical administration (1 g/kg body weight) were investigated over a 21 day period in male Wistar rats using metabonomic analysis of (1)H NMR spectra of urine, serum and liver tissue aqueous extracts. Liver and kidney histopathology examination and serum clinical chemistry analyses were also performed. (1)H NMR spectra and pattern recognition analyses from realgar treated animals showed increased excretion of urinary Kreb's cycle intermediates, increased levels of ketone bodies in urine and serum, and decreased levels of hepatic glucose and glycogen, as well as hypoglycemia and hyperlipoidemia, suggesting the perturbation of energy metabolism. Elevated levels of choline containing metabolites and betaine in serum and liver tissue aqueous extracts and increased serum creatine indicated altered transmethylation. Decreased urinary levels of trimethylamine-N-oxide, phenylacetylglycine and hippurate suggested the effects on the gut microflora environment by realgar. Signs of impairment of amino acid metabolism were supported by increased hepatic glutamate levels, increased methionine and decreased alanine levels in serum, and hypertaurinuria. The observed increase in glutathione in liver tissue aqueous extracts could be a biomarker of realgar induced oxidative injury. Serum clinical chemistry analyses showed increased levels of lactate dehydrogenase, aspartate aminotransferase, and alkaline phosphatase as well as increased levels of blood urea nitrogen and creatinine, indicating slight liver and kidney injury. The time-dependent biochemical variations induced by realgar were achieved using pattern recognition methods. This work illustrated the high reliability of NMR-based metabonomic approach on the study of the biochemical effects induced by traditional Chinese medicine.
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PMID:Metabolic profiling studies on the toxicological effects of realgar in rats by (1)H NMR spectroscopy. 1907 2

AspT, the aspartate:alanine antiporter of Tetragenococcus halophilus, a membrane protein of 543 amino acids with 10 putative transmembrane (TM) helices, is the prototype of the aspartate:alanine exchanger (AAE) family of transporters. Because TM3 (isoleucine 64 to methionine 85) has many amino acid residues that are conserved among members of the AAE family and because TM3 contains two charged residues and four polar residues, it is thought to be located near (or to form part of) the substrate translocation pathway that includes the binding site for the substrates. To elucidate the role of TM3 in the transport process, we carried out cysteine-scanning mutagenesis. The substitutions of tyrosine 75 and serine 84 had the strongest inhibitory effects on transport (initial rates of l-aspartate transport were below 15% of the rate for cysteine-less AspT). Considerable but less-marked effects were observed upon the replacement of methionine 70, phenylalanine 71, glycine 74, arginine 76, serine 83, and methionine 85 (initial rates between 15% and 30% of the rate for cysteine-less AspT). Introduced cysteine residues at the cytoplasmic half of TM3 could be labeled with Oregon green maleimide (OGM), whereas cysteines close to the periplasmic half (residues 64 to 75) were not labeled. These results suggest that TM3 has a hydrophobic core on the periplasmic half and that hydrophilic residues on the cytoplasmic half of TM3 participate in the formation of an aqueous cavity in membranes. Furthermore, the presence of l-aspartate protected the cysteine introduced at glycine 62 against a reaction with OGM. In contrast, l-aspartate stimulated the reactivity of the cysteine introduced at proline 79 with OGM. These results demonstrate that TM3 undergoes l-aspartate-induced conformational alterations. In addition, nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses and a glutaraldehyde cross-linking assay suggest that functional AspT forms homo-oligomers as a functional unit.
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PMID:Structural and functional importance of transmembrane domain 3 (TM3) in the aspartate:alanine antiporter AspT: topology and function of the residues of TM3 and oligomerization of AspT. 1918 16

It is documented that hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis, but whether elevated plasma homocysteine contributes to the progression of atherosclerosis in aged animals with hypercholesterolemia is still unknown. HHcy was induced in apolipoprotein E (ApoE) knockout mice (male, 32 weeks old) by feeding 2% methionine/low folate (1 mg/kg) diet for 20 weeks. HHcy induced by methionine feeding significantly increased oxidative stress, as measured by thiobarbituric-reactive substances in livers (P < .05) and genetic expression of Cu,Zn-superoxide dismutase, in methionine-fed animals compared with controls (P < .05). Furthermore, lipoprotein profiles were changed, in that low-density lipoprotein-cholesterol was shifted to very low-density lipoprotein in the methionine-supplemented group. However, nuclear factor kappaB activity, atherosclerotic lesions, hepatic glutathione level, lipid profiles, and activities of aspartate aminotransferase and alanine aminotransferase were not significantly different. These findings suggest that HHcy induced by methionine may promote disturbances in lipid peroxidation and modify lipoprotein metabolism but not contribute to the progression of atherosclerotic lesion in aged ApoE knockout mice.
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PMID:Methionine-induced hyperhomocysteinemia modulates lipoprotein profile and oxidative stress but not progression of atherosclerosis in aged apolipoprotein E knockout mice. 1929 7

In the present study we evaluated the effect of chronic methionine administration on oxidative stress and biochemical parameters in liver and serum of rats, respectively. We also performed histological analysis in liver. Results showed that hypermethioninemia increased chemiluminescence, carbonyl content and glutathione peroxidase activity, decreased total antioxidant potential, as well as altered catalase activity. Hypermethioninemia increased synthesis and concentration of glycogen, besides histological studies showed morphological alterations and reduction in the glycogen/glycoprotein content in liver. Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and glucose were increased in hypermethioninemic rats. These findings suggest that oxidative damage and histological changes caused by methionine may be related to the hepatic injury observed in hypermethioninemia.
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PMID:Hypermethioninemia provokes oxidative damage and histological changes in liver of rats. 1942 80


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