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)

A subfamily I aminotransferase gene homologue containing an open reading frame encoding 381 amino acid residues (Mr=42,271) has been identified in the process of the genome project of an extremely thermophilic bacterium, Thermus thermophilus HB8. Alignment of the predicted amino acid sequence using FASTA shows that this protein is a member of aminotransferase subfamily Igamma. The protein shows around 40% identity with both T. thermophilus aspartate aminotransferase [EC 2.6.1.1] and mammalian glutamine:phenylpyruvate aminotransferase [EC 2.6.1.64]. The recombinant protein expressed in Escherichia coli is a homodimer with a subunit molecular weight of 42,000, has one pyridoxal 5'-phosphate per subunit, and is highly active toward glutamine, methionine, aromatic amino acids, and corresponding keto acids, but has no preference for alanine and dicarboxylic amino acids. These substrate specificities are similar to those described for mammalian glutamine: phenylpyruvate aminotransferase. This is the first enzyme reported so far that has the glutamine aminotransferase activity in non-eukaryotic cells. As the presence of aromatic amino acid:2-oxoglutarate aminotransferase [EC 2.6.1.57] has not been reported in T. thermophilus, this enzyme is expected to catalyze the last transamination step of phenylalanine and tyrosine biosynthesis. It may also be involved in the methionine regeneration pathway associated with polyamine biosynthesis. The enzyme shows a strikingly high pKa value (9.3) of the coenzyme Schiff base in comparison with other subfamily I aminotransferases. The origin of this unique pKa value and the substrate specificity is discussed based on the previous crystallographic data of T. thermophilus and E. coli aspartate aminotransferases.
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PMID:Glutamine:phenylpyruvate aminotransferase from an extremely thermophilic bacterium, Thermus thermophilus HB8. 1476 73

Great progress has been made in the study of fatty liver with integrated traditional Chinese and western medicine in aspects of diagnosis, treatment and experimental study, etc. Most researches were designed to utilize diagnostic or model replicating method of western medicine to observe the effects or investigate the action mechanism of compound recipe, single Chinese herb or effective ingredients of Chinese herbs on fatty liver. According to the pathological mechanism of traditional Chinese medicine (TCM), fatty liver is characterized by deficiency in nature and repletion in appearance, which involves three Zang viscera such as liver, spleen and kidney and manifests as spleen Qi deficiency, liver and kidney deficiency, phlegm and dampness heaping internally, and Qi stagnation and blood stasis. This facilitates us to use specific recipe or modified recipe to treat fatty liver from the points of integrated traditional Chinese and western medicine and combining syndrome differentiation with disease differentiation. With gratifying achievement, this kind of approach has been the mainstream of the research on fatty liver and many researchers have reached an agreement on this point domestically. Spleen Fortifying and Blood Invigorating Recipe (SFBVER in brief, invented by our institute) can significantly improve the B ultrasound outcome of the liver in patients with fatty liver, with significant difference in B ultrasound scoring between pre-and post-treatment. It can alleviate the patients' symptoms, improve or regain liver function, decrease waist/buttocks ratio and the content of triglyceride and cholesterol in blood. SFBVER is superior to Dongbao Gantai Recipe in general effective rate. Experimental study also reveals that SFBVER can alleviate CCl(4) induced liver cell fatty degeneration and the inflammatory cell infiltration in rats, decrease the activities of ALT and AST, lower the content of triglyceride in liver, recover SOD activity in liver to normal level. The overall efficacy of SFBVER is superior to that of Dongbao Gantai Recipe. Further correlated study should be focused on inventing new preparation of traditional Chinese medicine and investigating its action mechanism with the guiding of the theory of TCM and referring to the latest discovery in fatty liver research in modern medicine.
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PMID:[Studies on treatment of fatty liver with traditional Chinese medicine]. 1533 89

The hepatoprotective effects of the extract of Terminalia catappa L. leaves (TCE) against D-Galactosamine (D-GalN)-induced liver injury and the mechanisms underlying its protection were studied. In acute hepatic injury test, it was found that serum ALT activity was remarkably increased (3.35-fold) after injection of D-GalN in mice. But with oral pretreatment of TCE (20, 50 and 100 mg/kg/d) for 7days, change in serum ALT was notably reversed. In primary cultured hepatocytes from fetal mice, it was found that cell viability was decreased by 45.0% after addition of D-GalN, while incubation with TCE (0.1, 0.5 and 1.0 mg/ml) for 36 hours could prevent the decrease in a dose-dependent manner. Meanwhile, D-GalN-induced both the increase of AST level (1.9-fold) and the decrease of SOD activity (48.0%) in supernatant of primary cultured hepatocytes could also be inhibited by pretreatment with TCE. In order to study the possible mechanisms underlying its hepatoprotective effects, one effective component separated from TCE, 2alpha, 3beta, 23-trihydroxyursane-12-en-28-oic acid (DHUA), was used to determine anti-mitochondrial swelling activity and superoxide radicals scavenging activity in vitro. It was found that at the concentration range of 50-500 micromol/L DHUA, Ca2+ -induced mitochondrial swelling was dose-dependently inhibited, and superoxide radicals scavenging activity was also shown in a dose-dependent manner. It was concluded that TCE has hepatoprotective activity and the mechanisms underlying its protective effects may be related to the direct mitochondrion protection and strong scavenging activity on reactive oxygen species (ROS).
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PMID:Mechanisms of hepatoprotection of Terminalia catappa L. extract on D-Galactosamine-induced liver damage. 1548 41

This study examined the effects of celecoxib on hepatic ischemia/reperfusion (I/R) injury in rats. A total of 40 male Sprague-Dawley rats weighing 190-210g were randomized into 4 groups of 10: (1) controls: data from unmanipulated animals; (2) sham group: rats subjected to the surgical procedure, except for liver I/R, and given saline; (3) I/R group: rats that underwent liver ischemia for 1h followed by reperfusion for 45min; (4) I-R/Celecoxib group: rats pretreated with celecoxib (3mgkg(-1), i.p.) 40min before liver I/R. Tc-99m sulfur colloid images were used to measure the uptake ratio and perfusion index. Liver tissues were taken to determine SOD, CAT, GSH-Px, and MDA levels and for biochemical and histological evaluation. The plasma ALT, AST, GGT, and LDH activities were higher in group 3 than in group 4. The uptake ratio was significantly lower in group 3 compared to groups 1, 2, and 4. In addition, in group 4, the uptake ratio and perfusion index were also significantly higher compared to group 3. MDA values and the hepatic injury score decreased, while the SOD, CAT, and GSH-Px values increased in group 4 compared to group 3. In group 3, hepatocytes were swollen with marked vacuolization. Group 4 showed well preserved liver parenchyma with hepatocytes arranged radially around the central vein; there were regular sinusoidal structures with normal morphology without any signs of congestion. We showed that celecoxib has beneficial effects in hepatic I/R injury and may protect the liver.
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PMID:The effect of celecoxib, a selective COX-2 inhibitor, on liver ischemia/reperfusion-induced oxidative stress in rats. 1638 42

The study was aimed at evaluating the antioxidant activity of alcoholic extract of Cassia siamea Lam. (Fabaceae) flowers. The extract was found to contain a large amount of polyphenols and also exhibited an immense reducing ability. At a concentration of 250 microg/ml, 96% of DPPH radicals and at 500 microg/ml, 42.7, 32.7 and 64.5% of O2-, H2O2 and NO respectively could be scavenged by C. siamea flower extract. The extract also inhibited OH radical induced oxidation of protein (BSA) and LPO in murine hepatic microsomes. The determination of metal chelating capacity of the extract indicated chelating of metal ions (Fe2+) to be a putative mechanism implicated in the inhibition of OH radical-induced BSA oxidation and LPO. C. siamea flower extract also exhibited a significant antioxidant activity in acute oxidative tissue injury animal model constituted by CCl4 induced hepatotoxicity. Oral administration of the extract at a dose of 50-150 mg/kg of body weight significantly protected from CCl4 induced elevation in AST and ALT in the serum, elevation in hepatic LPO, depletion of hepatic GSH and decrease in the activities of hepatic antioxidant enzymes: SOD, CAT and GPX. The extract also protected against histopathological changes produced by CCl4 such as necrosis, fatty changes, ballooning degeneration, etc. The data obtained in the present study suggests that the alcoholic extract of C. siamea flowers have potent antioxidant activity against free radicals, prevent oxidative damage to major biomolecules and afford significant protection against oxidative damage in the liver.
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PMID:Evaluation of antioxidant activity of Cassia siamea flowers. 1684 7

The aminotransferase (BtrR), which is involved in the biosynthesis of butirosin, a 2-deoxystreptamine (2-DOS)-containing aminoglycoside antibiotic produced by Bacillus circulans, catalyses the pyridoxal phosphate (PLP)-dependent transamination reaction both of 2-deoxy-scyllo-inosose to 2-deoxy-scyllo-inosamine and of amino-dideoxy-scyllo-inosose to 2-DOS. The high-resolution crystal structures of the PLP- and PMP-bound forms of BtrR aminotransferase from B. circulans were solved at resolutions of 2.1 A and 1.7 A with R(factor)/R(free) values of 17.4/20.6 and 19.9/21.9, respectively. BtrR has a fold characteristic of the aspartate aminotransferase family, and sequence and structure analysis categorises it as a member of SMAT (secondary metabolite aminotransferases) subfamily. It exists as a homodimer with two active sites per dimer. The active site of the BtrR protomer is located in a cleft between an alpha helical N-terminus, a central alphabetaalpha sandwich domain and an alphabeta C-terminal domain. The structures of the PLP- and PMP-bound enzymes are very similar; however BtrR-PMP lacks the covalent bond to Lys192. Furthermore, the two forms differ in the side-chain conformations of Trp92, Asp163, and Tyr342 that are likely to be important in substrate selectivity and substrate binding. This is the first three-dimensional structure of an enzyme from the butirosin biosynthesis gene cluster.
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PMID:Crystal structures of the PLP- and PMP-bound forms of BtrR, a dual functional aminotransferase involved in butirosin biosynthesis. 1689 11

Cisplatin (CDDP) is a widely used anticancer drug, but at high dose, it can produce undesirable side effects such as hepatotoxicity. Because silymrin has been used to treat liver disorders, the protective effect of silymarin on CDDP-induced hepatotoxicity was evaluated in rats. Hepatotoxicity was determined by changes in serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST], nitric oxide [NO] levels, albumin and calcium levels, and superoxide dismutase [SOD], glutathione peroxidase [GSHPx] activities, glutathione content, malondialdehyde [MDA] and nitric oxide [NO] levels in liver tissue of rats. Male albino rats were divided into four groups, 10 rats in each. In the control group, rats were injected i.p. with 0.2 ml of propylene glycol in saline 75/25 (v/v) for 5 consecutive days [Silymarin was dissolved in 0.2 ml of propylene glycol in saline 75/25 v/v]. The second group were injected with CDDP (7.5 mg /kg, I.P.), whereas animals in the third group were i.p. injected with silymarin at a dose of 100 mg/kg/day for 5 consecutive days. The Fourth group received a daily i.p. injection of silymarin (100 mg/kg/day for 5 days) 1 hr before a single i.p. injection of CDDP (7.5 mg/kg). CDDP hepatotoxicity was manifested biochemically by an increase in serum ALT and AST, elevation of MDA and NO in liver tissues as well as a decrease in GSH and the activities of antioxidant enzymes, including SOD, GSHPx in liver tissues. In addition, marked decrease in serum NO, albumin and calcium levels were observed. Serum ALT, AST, liver NO level, MDA was found to decreased in the combination group in comparison with the CDDP group. The activities of SOD, GSHPx, GSH and serum NO were lower in CDDP group than both the control and CDDP pretreated with silymarin groups. The results obtained suggested that silymarin significantly attenuated the hepatotoxicity as an indirect target of CDDP in an animal model of CDDP-induced nephrotoxicity.
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PMID:Silymarin modulates Cisplatin-induced oxidative stress and hepatotoxicity in rats. 1712 99

The aim of this study was to investigate the possible protective effects of echinacoside, one of the phenylethanoids isolated from the stems of Cistanches salsa, a Chinese herbal medicine, on the free radical damage of liver caused by carbon tetrachloride in rats. Treatment of rats with carbon tetrachloride produced severe liver injury, as demonstrated by dramatic elevation of serum ALT, AST levels and typical histopathological changes including hepatocyte necrosis or apoptosis, haemorrhage, fatty degeneration, etc. In addition, carbon tetrachloride administration caused oxidative stress in rats, as evidenced by increased reactive oxygen species (ROS) production and MDA concentrations in the liver of rats, along with a remarkable reduction in hepatic SOD activity and GSH content. However, simultaneous treatment with echinacoside (50mg/kg, intraperitoneally) significantly attenuated carbon tetrachloride-induced hepatotoxicity. The results showed that serum ALT, AST levels and hepatic MDA content as well as ROS production were reduced dramatically, and hepatic SOD activity and GSH content were restored remarkably by echinacoside administration, as compared to the carbon tetrachloride-treated rats. Moreover, the histopathological damage of liver and the number of apoptotic hepatocytes were also significantly ameliorated by echinacoside treatment. It is therefore suggested that echinacoside can provide a definite protective effect against acute hepatic injury caused by CCl(4) in rats, which may mainly be associated with its antioxidative effect.
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PMID:Protective effects of echinacoside on carbon tetrachloride-induced hepatotoxicity in rats. 1722 97

The hepatoprotective and antioxidant effect of Cassia fistula Linn. leaf extract on liver injury induced by diethylnitrosamine (DEN) was investigated. Wistar rats weighing 200+/-10g were administered a single dose of DEN (200mg/kg b.w., i.p.) and left for 30 days. For hepatoprotective studies, ethanolic leaf extract (ELE) of C. fistula Linn. (500mg/kg b.w., p.o.) was administered daily for 30 days. AST, ALT, ALP, LDH, gamma-GT and bilirubin were estimated in serum and liver tissue. Lipid peroxidation (LPO), SOD and CAT were also estimated in liver tissue as markers of oxidative stress. DEN induced hepatotoxicity in all the treated animals were evident by elevated serum ALT, AST, ALP and bilirubin levels and a simultaneous fall in their levels in the liver tissue after 30 days. Induction of oxidative stress in the liver was evidenced by increased LPO and fall in the activities of SOD and CAT. ELE administration for 30 days prevented the DEN induced hepatic injury and oxidative stress. In conclusion, it was observed that ELE of C. fistula Linn. protects the liver against DEN induced hepatic injury in rats.
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PMID:Effect of Cassia fistula Linn. leaf extract on diethylnitrosamine induced hepatic injury in rats. 1728 8

While the urea-mediated unfolding pathway of the Escherichia coli aspartate aminotransferase (eAATase) homodimer proceeds through a reversible three-state process with a partially folded dimeric intermediate, D D* 2U (E. Deu and J. F. Kirsch, accompanying paper), that of a cofactor-stabilized form differs. Pyridoxal phosphate, which binds at the intersubunit active sites, stabilizes the native form by 6 kcal mol-1 and dissociates during the D <==> D* transition. Reductive trapping of the cofactor to a nondissociable derivative (PPL-eAATase) precludes the formation of D*. A novel monomeric intermediate (M'-PPL) with 70% of the native secondary structure (circular dichroism) was identified in the unfolding pathway of PPL-eAATase: D-PPL2 <==> 2M'-PPL <==> 2U-PPL. The combined results define two structural regions with distinct stabilities: the active site region (ASR) and the generally more stable, dimerization region (DMR). The DMR includes the key intersubunit contacts. It is responsible for the multimeric nature of D*, and its disorder leads to dimer dissociation. Selective strengthening of the ASR-cofactor interactions by cofactor trapping reverses the relative stabilities of the two regions (from DMR > ASR in the apoenzyme to ASR > DMR in PPL-eAATase) and results in a reordering of the eAATase denaturation pathway.
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PMID:Cofactor-directed reversible denaturation pathways: the cofactor-stabilized Escherichia coli aspartate aminotransferase homodimer unfolds through a pathway that differs from that of the apoenzyme. 1744 30


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