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

---

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

Tyrosine, added to the growth medium of a strain of Escherichia coli K-12 lacking transaminase B, repressed the tyrosine, phenylalanine, and tryptophan aminotransferase activities while leaving the aspartate aminotransferase activity unchanged. This suggested that the aspartate and the aromatic aminotransferase activities, previously believed to reside in the same protein, viz. transaminase A, are actually nonidentical. Further experiments showed that, upon incubation at 55 C, the aspartate aminotransferase of crude extracts was almost completely stable, whereas the tyrosine and phenylalanine activities were rapidly inactivated. Apoenzyme formation was faster, and apoenzyme degradation proceeded more slowly with aspartate aminotransferase than with tyrosine aminotransferase. Electrophoresis in polyacrylamide gels separated the aminotransferases. A more rapidly moving band contained tyrosine, phenylalanine, and tryptophan aminotransferases, and a slower band contained aspartate aminotransferase. A mutant of E. coli K-12 with low levels of aspartate aminotransferase exhibited unchanged levels of tyrosine aminotransferase. Thus, transaminase A appears to be made up of at least two proteins: one of broad specificity whose synthesis is repressed by tyrosine and another, specific for aspartate, which is not subject to repression by amino acids. The apparent molecular weights of both the aspartate and the aromatic aminotransferases, determined by gel filtration, were about 100,000.
...
PMID:Nonidentity of the aspartate and the aromatic aminotransferase components of transaminase A in Escherichia coli. 440 56

1. In order to assess the effects of oestrogens on the metabolism of tryptophan and vitamin B6, ovariectomized rats have been maintained on diets providing known amounts of tryptophan, nicotinamide and vitamin B6. They received oestrone sulphate, 210 micrograms/kg body-wt per d, either incorporated in the diet for 8 weeks, or by daily intraperitoneal injection for periods of 1-3 d. 2. Oestrone sulphate administration caused a slight reduction in the concentration of pyridoxal phosphate in plasma. It had no effect on the concentration of pyridoxal phosphate in liver or kidney, the urinary excretion of 4-pyridoxic acid, the activation of erythrocyte aspartate aminotransferase (L-aspartate:2-oxo-glutarate aminotransferase, EC 2. 6. 1. 1) by incubation with added pyridoxal phosphate, or the activity of pyridoxal oxidase (aldehyde:oxygen oxido-reductase, EC 1.2.3.1) in the liver. 3. Oestrone sulphate administration caused an increase in the urinary excretion of kynurenine and a reduction in the activity of liver kynureninase (L-kynurenine hydrolase, EC 3.7.1.3). It had no effect on the urinary excretion of N1-methyl nicotinamide or the concentrations of nicotinamide nucleotides in blood, liver or kidney. 4. There was a considerable excess of the apoenzyme of kynureninase in the liver. Incubation of liver homogenates with added pyridoxal phosphate led to a 4- to 5-fold increase in activity. 5. We conclude that there is no evidence of any significant effect of oestrogens on vitamin B6. It is suggested that abnormalities of tryptophan metabolism in women receiving oestrogens, which have been widely attributed to drug-induced vitamin B6 depletion, can be accounted for by inhibition of kynureninase by oestrogen metabolites.
...
PMID:Effects of oestrogen administration on vitamin B6 and tryptophan metabolism in the rat. 628 3

Inactivation of the beta 2 subunit and of the alpha 2 beta 2 complex of tryptophan synthase of Escherichia coli by the arginine-specific dicarbonyl reagent phenylglyoxal results from modification of one arginyl residue per beta monomer. The substrate L-serine protects the holo beta 2 subunit and the holo alpha 2 beta 2 complex from both inactivation and arginine modification but has no effect on the inactivation or modification of the apo forms of the enzyme. This result and the finding that phenylglyoxal competes with L-serine in reactions catalyzed by both the holo beta 2 subunit and the holo alpha 2 beta 2 complex indicate that L-serine and phenylglyoxal both bind to the same essential arginyl residue in the holo beta 2 subunit. The apo beta 2 subunit is protected from phenylglyoxal inactivation much more effectively by phosphopyridoxyl-L-serine than by either pyridoxal phosphate or pyridoxine phosphate, both of which lack the L-serine moiety. The phenylglyoxal-modified apo beta 2 subunit binds pyridoxal phosphate and the alpha subunit but cannot bind L-serine or L-tryptophan. We conclude that the alpha-carboxyl group of L-serine and not the phosphate of pyridoxal phosphate binds to the essential arginyl residue in the beta 2 subunit. The specific arginyl residue in the beta 2 subunit which is protected by L-serine from modification by phenyl[2-14C]glyoxal has been identified as arginine-148 by isolating a labeled cyanogen bromide fragment (residues 135-149) and by digesting this fragment with pepsin to yield the labeled dipeptide arginine-methionine (residues 148-149). The primary sequence near arginine-148 contains three other basic residues (lysine-137, arginine-141, and arginine-150) which may facilitate anion binding and increase the reactivity of arginine-148. The conservation of the arginine residues 141, 148, and 150 in the sequences of tryptophan synthase from E. coli, Salmonella typhimurium, and yeast supports a functional role for these three residues in anion binding. The location and role of the active-site arginyl residues in the beta 2 subunit and in two other enzymes which contain pyridoxal phosphate, aspartate aminotransferase and glycogen phosphorylase, are compared.
...
PMID:L-serine binds to arginine-148 of the beta 2 subunit of Escherichia coli tryptophan synthase. 641 46

The substrate specificity of aspartate aminotransferase (ASAT, E.C. 2.6.1.1.) from Leishmania was examined following observations of artefacts on gels stained for alanine aminotransferase (ALAT, E.C. 2.6.1.2.) after thin-layer starch-gel electrophoresis. Leishmanial ASAT acted on L-aspartate, L-alanine, L-tryptophan and L-tyrosine. Interpretation of ALAT zymograms must thus take into account the presence of interfering ASAT bands, and the need is emphasized for rigorous controls in isoenzyme electrophoresis.
...
PMID:Aspartate aminotransferase in Leishmania is a broad-spectrum transaminase. 646 33

The concept of this basic research was that monosodium L-glutamate could reveal a deficiency of vitamin B6 by the neurological reactions known as the Chinese Restaurant Syndrome. An other amino acid, tryptophan, administered to subjects, is known to reveal a deficiency of vitamin B6 by the excretory xanthurenic acid, etc. The presence and degree of a deficiency of vitamin B6 in 155 students on no supplemental B6 was determined by the differential assay of aspartate transaminase of erythrocytes which also allows each subject to be a control. Twenty-seven of 155 students had extraordinarily low basal specific activities of the transaminase, less than 0.26 mumol pyruvate/(h X 10(8) erythrocytes). These 27 were challenged with glutamate and a placebo. Twelve of 27 revealed the Chinese Restaurant Syndrome, and 15 did not. By double blind trials, the 12 "responders" were treated with pyridoxine and a placebo for twelve weeks, and then were rechallenged with glutamate and a placebo. Decoding showed 3 of 12 received placebo to pyridoxine and then revealed the symptoms of the syndrome again to glutamate; 9 of 12 received pyridoxine and then 8 of 9 failed to respond to glutamate. These results show, p less than 0.01, that the symptoms of the Chinese Restaurant Syndrome to oral glutamate fail to reoccur after treatment which pyridoxine, and that the biochemistry of vitamin B6 is basic to the cause of the Chinese Restaurant Syndrome.
...
PMID:The biochemistry of vitamin B6 is basic to the cause of the Chinese restaurant syndrome. 672 32

We describe the complete purification of aromatic aminotransferase I, the enzyme responsible for the ability of Klebsiella aerogenes to use tryptophan and phenylalanine as sole sources of nitrogen, as well as the partial purification of aromatic aminotransferase IV. An examination of the properties of these enzymes revealed that aminotransferase I had much greater affinity for the aromatic amino acids than aminotransferase IV, explaining the essential role of aminotransferase I in the utilization of exogenously supplied aromatic amino acids. The properties of aminotransferase IV suggest that this enzyme is actually an aspartate aminotransferase (EC 2.6.1.1), corresponding to the product of the aspC gene of Escherichia coli.
...
PMID:Purification and properties of aromatic amino acid aminotransferase from Klebsiella aerogenes. 700 15

Fed and fasted rats were injected with L-tryptophan (12.5 mg/100 g body weight) and the specific activities of L-glutamic: NAD oxidoreductase (deaminating) (EC 1.4.1.2) (GDH), L-aspartic-2-ketoglutaric aminotransferase (EC 2.6.1.1) (GOT) and L-alanine-2-ketoglutaric aminotransferase (EC 2.6.1.2) (GPT) from hepatic mitochondria and cytosol were compared. L-tryptophan results in a decrease of mitochondrial GDH activity by 22% and of cytosolic GPT and GOT by 42% and 38% respectively in the liver of fasted rats. Xanthurenate is a potent inhibitor of purified extramitochondrial GPT, whereas anthranilate and quinolinate are less potent inhibitors. L-tryptophan, 5-OH-tryptophan and indole exert a slight inhibition. Kynurenine, 5-OH-tryptamine, tryptamine, picolinic acid, nicotinic acid and indoloacetic acid do not show any inhibition of GPT. It is suggested that L-tryptophan injection inhibits extramitochondrial GPT by its transformation to xanthurenate and anthranilate.
...
PMID:Effect of L-tryptophan injection in rats on some enzymes of amino acid metabolism in liver. I. In vitro studies of the effect of L-tryptophan and its metabolites on the extramitochondrial L-alanine: 2-ketoglutaric aminotransferase. 722 74

Acute hepatic ischaemia was induced in pigs by means of a portacaval shunt with hepatic artery ligation after 24 hours. Despite significant elevation in blood ammonia, fatty acids, aspartate aminotransferase, cerebrospinal fluid glutamine and ammonia, and brain tissue glutamine, ammonia and tryptophan, the experimental animals remained awake and alert and indistinguishable from sham-operated controls. The molar ratio of branched-chain to aromatic amino acids fell sharply in the arterial blood, but showed a terminal attempt at compensation in muscle venous samples. Portal and muscle venous insulin levels were elevated, and glucagon values rose in all circulation segments in the experimental group. The failure to induce coma in these pigs, despite the presence of many of the classical biochemical features, suggests that the syndrome of encephalopathy comprises several stages, and that the pig may be an important model in which to define these.
...
PMID:Acute hepatic ischaemia in the pig- the changes in plasma hormones, amino acids and brain biochemistry. 725 Aug 93

Vitamin B6 deficiency led to a decrease in aspartate: 2-oxoglutarate aminotransferase activity and to a marked increase in phenylalanine:2-oxoglutarate aminotransferase activity in rat small intestines. The increased phenylalanine aminotransferase activity was found to be due to a newly appeared aromatic aminotransferase without the aspartate aminotransferase activity in the cytosol of the small intestinal mucosa. The enzyme preparation had an isoelectric point of pH 8.5, a pH optimum near 8.0, and a molecular weight of approximately 100,000 with two identical subunits. The enzyme showed aminotransferase activities towards various aromatic L-amino acids with 2-oxoglutarate as the amino acceptor. The order of effectiveness of aromatic L-amino acids was phenylalanine > tryptophan > tyrosine > 5-hydroxytryptophan; very little activity was detected with other L-amino acids that were tested. The enzyme was specific for 2-oxoglutarate as the amino acceptor. The enzyme was not detected in other tissues (liver, kidney, heart, and brain) from both control and vitamin B6-deficient rats. The enzyme has never been described before in animal tissues.
...
PMID:The appearance of a new aromatic aminotransferase in the small intestines of vitamin B6-deficient rats. 743 Jan 6

In an attempt to change the reaction and substrate specificity of aspartate aminotransferase, several apolar active-site residues were substituted in turn with a histidine residue. Aspartate aminotransferase W140H (of Escherichia coli) racemizes alanine seven times faster (Kcat' = 2.2 x 10(-4) s-1) than the wild-type enzyme, while the aminotransferase activity toward L-alanine was sixfold decreased. X-ray crystallographic analysis showed that the structural changes brought about by the mutation are limited to the immediate environment of H140. In contrast to the tryptophan side chain in the wild-type structure, the imidazole ring of H140 does not form a stacking interaction with the coenzyme pyridine ring. The angle between the two ring planes is about 50 degrees. Pyridoxamine 5'-phosphate dissociates 50 times more rapidly from the W140H mutant than from the wild-type enzyme. A model of the structure of the quinonoid enzyme substrate intermediate indicates that H140 might assist in the reprotonation of C alpha of the amino acid substrate from the re side of the deprotonated coenzyme-substrate adduct in competition with si-side reprotonation by K258. In aspartate aminotransferase I17H (of chicken mitochondria), the substituted residue also lies on the re side of the coenzyme. This mutant enzyme slowly decarboxylates L-aspartate to L-alanine (Kcat' = 8 x 10(-5) s-1). No beta-decarboxylase activity is detectable in the wild-type enzyme. In aspartate aminotransferase V37H (of chicken mitochondria), the mutated residue lies besides the coenzyme in the plane of the pyridine ring; no change in reaction specificity was observed. All three mutations, i.e. W140-->H, I17-->H and V37--H, decreased the aminotransferase activity toward aromatic amino acids by 10-100-fold, while decreasing the activity toward dicarboxylic substrates only moderately to 20%, 20% and 60% of the activity of the wild-type enzymes, respectively. In all three mutant enzymes, the decrease in aspartate aminotransferase activity at pH values lower than 6.5 was more pronounced than in the wild-type enzyme, apparently due to the protonation of the newly introduced histidine residues. The study shows that substitutions of single active-site residues may result in altered reaction and substrate specificities of pyridoxal-5'-phosphate-dependent enzymes.
...
PMID:Substitution of apolar residues in the active site of aspartate aminotransferase by histidine. Effects on reaction and substrate specificity. 785 26


<< Previous 1 2 3 4 5 6 7 8 Next >>

---