Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The homology of subunit primary sequence of 40 glutamate decarboxylases (GAD) of different origin was analyzed by multiple alignment. A phylogenetic tree was designed on the basis of the resulting data. The following groups are distinguished in the consensus tree: archeans, bacteria, plant eukaryotes, and animal eukaryotes. The latter are clearly divided into two branches according to two enzyme isoforms. Borders of PLP domains in each enzyme were detected. The consensus phylogenetic tree for PLP domains is structurally rather similar to that obtained for subunits. Twenty homologous motifs of from 15 to 87 amino acid residues were revealed in all GAD studied. The results revealed the division of all of the enzymes into groups with characteristic sets of motifs in each and a fixed order of their arrangement along the sequence. Thus, we can show the divergent evolution of the enzyme. The results of multiple alignments during structural analysis of the 40 GAD confirmed and extended our previous data on conserved residues that arrange the position of the coenzyme (PLP) in the enzyme active center. The following residues should be noted: lysine forming a Schiff base with the PLP aldehyde group, an adjacent histidine, and aspartic acid that establishes a link with nitrogen of the PLP pyridine ring. The homology of the primary sequence fragments was also found in the residues in contact with the PLP phosphate group. Comparison of the GAD amino acid sequence with that of another PLP enzyme, aspartate aminotransferase, revealed a binding site for carboxylic group of the substrate--glutamic acid. The structures carrying out a particular catalytic function of all GAD studied were detected, i.e., convergent evolution of the enzyme was revealed.
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PMID:Glutamate decarboxylase: computer studies of enzyme evolution. 1246 Jan 16

The variation in inhibitor specificity for five different amine inhibitors bound to CST, BT, and the cold-adapted AST has been studied by use of association constant measurements, structural analysis of high-resolution crystal structures, and the LIE method. Experimental data show that AST binds the 1BZA and 2BEA inhibitors 0.8 and 0.5 kcal/mole more strongly than BT. However, structural interactions and orientations of the inhibitors within the S1 site have been found to be virtually identical in the three enzymes studied. For example, the four water molecules in the inhibitor-free structures of AST and BT are channeled into similar positions in the S1 site, and the nitrogen atom(s) of the inhibitors are found in two cationic binding sites denoted Position1 and Position2. The hydrophobic binding contributions for all five inhibitors, estimated by the LIE calculations, are also in the same order (-2.1 +/- 0.2 kcal/mole) for all three enzymes. Our hypothesis is therefore that the observed variation in inhibitor binding arises from different electrostatic interactions originating from residues outside the S1 site. This is well illustrated by AST, in which Asp 150 and Glu 221B, despite some distance from the S1 binding site, lower the electrostatic potential of the S1 site and thus enhance substrate binding. Because the trends in the experimentally determined binding energies were reproduced by the LIE calculations after adding the contribution from long-range interactions, we find this method very suitable for rational studies of protein-substrate interactions.
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PMID:Trypsin specificity as elucidated by LIE calculations, X-ray structures, and association constant measurements. 1504 35

This study sought to investigate the ameliorating effects of soy 11S protein on the impacts of alcohol consumption in rat hepatocytes and in reducing total cholesterol levels and total lipid levels in the serum. Liver histology and the clinically important enzyme markers (Aspartate Aminotransferase: AST and Alanine Aminotransferase: ALT) of rats, administered with both alcohol and soy 11S protein treatments, were compared with those in the control group. The treatment regimen (11S soy protein extract) significantly reduced serum ALT and AST levels, indicating the hepato-protective effects of soy 11S protein. Furthermore, total cholesterol and total lipid levels were significantly reduced. In addition to preventing the presence of lipid droplets and secondary lysosomes, electron microscopy indicated that the administration of the soy 11S protein treatment preserved important hepatocyte structures. These results indicate that soy 11S protein can positively mediate the effects of alcohol on hepatocytes and general liver functions.
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PMID:Ameliorative effects of soy 11S protein on liver damage and hyperlipidemia in alcohol-fed rats. 1546 10

Nitrogen (N) is an essential requirement for kernel growth in maize (Zea mays); however, little is known about how N assimilates are metabolized in young earshoots during seed development. The objective of this study was to assess amino acid metabolism in cob and spikelet tissues during the critical 2 weeks following silking. Two maize hybrids were grown in the field for 2 years at two levels of supplemental N fertilizer (0 and 168 kg N/ha). The effects of the reproductive sink on cob N metabolism were examined by comparing pollinated to unpollinated earshoots. Earshoots were sampled at 2, 8, 14, and 18 d after silking; dissected into cob, spikelet, and/or pedicel and kernel fractions; then analyzed for amino acid profiles and key enzyme activities associated with amino acid metabolism. Major amino acids in the cob were glutamine (Gln), aspartic acid (Asp), asparagine (Asn), glutamate, and alanine. Gln concentrations dropped dramatically from 2 to 14 d after silking in both pollinated and unpollinated cobs, whereas all other measured amino acids accumulated over time in unpollinated spikelets and cobs, especially Asn. N supply had a variable effect on individual amino acid levels in young cobs and spikelets, with Asn being the most notably enhanced. We found that the cob performs significant enzymatic interconversions among Gln, alanine, Asp, and Asn during early reproductive development, which may precondition the N assimilate supply for sustained kernel growth. The measured amino acid profiles and enzymatic activities suggest that the Asn to Gln ratio in cobs may be part of a signal transduction pathway involving aspartate aminotransferase, Gln synthetase, and Asn synthetase to indicate plant N status for kernel development.
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PMID:Amino acid metabolism in maize earshoots. Implications for assimilate preconditioning and nitrogen signaling. 1553 10

AspT is an electrogenic aspartate:alanine exchange protein that represents the vectorial component of a proton-motive metabolic cycle found in some strains of Tetragenococcus halophilus. AspT is the sole member of a new family, the Aspartate: Alanine Exchanger (AAE) family, in secondary transporters, according to the computational classification proposed by Saier et al. (http://www.biology.ucsd.edu/~msaier/transport/). We analyzed the topology of AspT biochemically, by using fusion methods in combination with alkaline phosphatase or beta-lactamase. These results suggested that AspT has a unique topology; 8 TMS, a large cytoplasmic loop (183 amino acids) between TMS5 and TMS6, and N- and C-termini that both face the periplasm. These results demonstrated a unique 2D-structure of AspT as the novel AAE family.
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PMID:Membrane topology of the electrogenic aspartate-alanine antiporter AspT of Tetragenococcus halophilus. 1567 Jul 44

In aging tissues the oxidative stress increases due to decreased activity of antioxidant enzymes and proteolysis increases due to decreased activity of aminotransferases, which can be modified by hormonal replacement therapy (HRT). The aim of the present study was to determine the effect of HRT on the activities of an antioxidant enzyme superoxide dismutase (SOD) and aminotransferases like alanine aminotransferase (Ala-AT) and aspartate aminotransferase in different age groups (12, 18 and 24 months) of naturally menopausal rats. The rats were given the subcutaneous injection of 17beta-estradiol, progesterone and combination of estradiol and progesterone for 1 month. The activity of SOD, Ala-AT and Asp-AT was measured in the brain (cerebral hemisphere, CH), heart, liver, kidney and uterus. The activity of SOD decreased with age in all the tissues taken particularly in liver. After HRT the enzyme activities were increased as compared to age-matched controls in all the tissues of aging rats. The activities of transaminases (Ala-AT and Asp-AT) showed a decrease with age in all the tissues and administration of estradiol and combination of estradiol and progesterone further decreased both the aminotransferases. Our study elucidates that increased activity of SOD contributes in protection of cells from oxygen toxicity by catalyzing the dismutation of free radicals in tissues. Furthermore, the HRT probably decreases gluconeogenesis and proteolysis by decreasing the activities of Ala-AT and Asp-AT in aging rat tissues.
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PMID:Administration of estradiol and progesterone modulate the activities of antioxidant enzyme and aminotransferases in naturally menopausal rats. 1582 Jun 10

Two amide synthetic derivatives of 3,4-di(OH)-hydrocinnamate (HC), 3,4-dihydroxyphenylpropionic (l-serine methyl ester) amide (E030) and 3,4-dihydroxyphenylpropionic (l-aspartic acid) amide (E076), were investigated to compare their lipid-lowering efficacy with HC. Male rats were fed a 1 g/100 g high-cholesterol diet for 6 weeks with supplements of either clofibrate (0.02%, w/w), HC (0.025%, w/w), E030 (0.039%, w/w) or E076 (0.041%, w/w). The clofibrate supplement was used as a positive control for the lipid-lowering efficacy. The food intakes and body weight gains were not significantly different among the groups. The plasma and hepatic cholesterol and triglyceride levels were lower in clofibrate, HC, E030, and E076-supplemented groups compared to the control group. The supplementation of HC and its amide derivatives was as effective as clofibrate in increasing the ratio of HDL-cholesterol to total plasma cholesterol and reducing the atherogenic index (AI). The hepatic cholesterol level in the HC and E076 groups was significantly lower than that in the clofibrate group. The hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA reductase) and acyl-CoA:cholesterol acyltransferase (ACAT) activities were significantly lower in the all test groups than in the control group. The excretion of neutral sterol was significantly higher in the HC, E030, and E076-supplemented groups compared to the control group. The plasma AST and ALT activities, indirect indexes of hepatic toxicity, were significantly lower in the HC, E030, and E076-supplemented groups than in the control group. Accordingly, the current results suggest that E030 and E076, two amide synthetic derivatives of HC, are effective in lowering lipid activity.
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PMID:Anticholesterolemic effect of 3,4-di(OH)-phenylpropionic amides in high-cholesterol fed rats. 1616 59

An efficient procedure for the production of l-[4-13C]aspartic acid (4-13C-Asp) was investigated. In this procedure, phosphoenolpyruvate carboxylase originating from the methanol-assimilating microbe, Methylobacterium extorquens JCM 2805, was used for the production of labeled oxaloacetic acid from phosphoenolpyruvate (PEP) and NaH13CO3; the oxaloacetic acid was then converted to 4-13C-Asp with glutamic-oxaloacetic transaminase. In this reaction, with starting concentrations of 10 mM PEP, 10 mM NaH13CO3 and 15 mM L-glutamic acid (Glu), the yield was 70%. 4-13C-Asp and Glu in the final reaction mixture were separated by displacement chromatography. The yield of this process was 84%. The overall yield was 59%. The incorporation of 13C at the C-4 position of 4-13C-Asp was confirmed by NMR spectroscopy.
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PMID:Enzymatic synthesis of L-[4-13C]aspartic acid. 1623 66

A 48-year-old man was referred to Sakai Municipal Hospital with nasal discharge and right facial swelling. The pathological findings of a nasal cavity tumor revealed stage IIB NK/T-cell lymphoma. He was admitted to our hospital and received CHOP therapy, resulting in progressive disease. Irradiation therapy combined with DeVIC chemotherapy also could not shrink his lymphoma. Then, two courses of L-asparaginase(L-Asp) were administered, resulting in partial improvement of the nasal and pharynx lesions, resolution of the fever and improvement of his performance status. On the day before a third course of L-Asp, he again developed a lowgrade fever. Although L-Asp was administered for several days, marked elevation of serum LDH, AST, ALT level, and thrombocytopenia persisted, and he died. Post-mortem examinations revealed hemophagocytosis in the bone marrow and liver, and infiltration of lymphoma cells into multiple organs including left lower lung, liver, spleen and kidneys. Although L-Asp was effective against nasal NK/T-cell lymphoma resistant to combination chemotherapy and irradiation therapy, the effectiveness of the single agent with L-Asp was only transient. L-Asp based regimen should be used as first-line therapy if asparagine synthetase protein expression is low using an immunohistochemical method.
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PMID:[Temporary effective treatment with L-asparaginase for a patient with refractory nasal NK/T-cell lymphoma]. 1628 43

More than 70 allatostatins have been isolated from various insects and there is interest in the determination of their active conformation. We have synthesized Dippu-AST 1 (originally isolated from the cockroach Blattella germanica) and studied its conformation in solution by 2-D NMR and molecular modeling. Dippu-AST 1 belongs to the cockroach-type ASTs that have Y/FXFGL-NH(2) as the common C-terminal sequence. We found that Dippu-AST 1 forms a type I' beta-turn conformation in DMSO. We also studied the conformations of Dippu-AST 1 and six cockroach-type allatostatins in water using the molecular dynamics method. When the X amino acid in the consensus sequence Y/FXFGL-NH(2) is Ala or Ser, the allatostatin can form a typical type II beta-turn. If the X is Asp or Asn whose side chain contains a carbonyl, the allatostatin can form a type I, I' or IV beta-turn conformation; if the X is Gly, a closer gamma-turn is adopted. Our study indicates that the turn conformation is ubiquitous in cockroach-type allatostatins.
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PMID:The study of solution conformation of allatostatins by 2-D NMR and molecular modeling. 1630 39


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