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:2.6.1.44 (AGT)
770 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rhodopseudomonas acidophila strain 7050 assimilated ammonia via a constitutive glutamine synthetase/glutamate synthase enzyme system. Glutamine synthetase had a Km for NH+4 of 0.38 mM whilst the nicotinamide adenine dinucleotide linked glutamate synthase had a Km for glutamine of 0.55 mM. R. acidophila utilized only a limited range of amino acids as sole nitrogen sources: L-alanine, glutamine and asparagine. The bacterium did not grow on glutamate as sole nitrogen source and lacked glutamate dehydrogenase. When R. acidophila was grown on L-alanine as the sole nitrogen source in the absence of N2 low levels of a nicotinamide adenine dinucleotide linked L-alanine dehydrogenase were produced. It is concluded, therefore, that this reaction was not a significant route of ammonia assimilation in this bacterium except when glutamine synthetase was inhibited by methionine sulphoximine. In L-alanine grown cells the presence of an active alanine-glyoxylate aminotransferase and, on occasions, low levels of an alanine-oxaloacetate aminotransferase were detected. Alanine-2-oxo-glutarate aminotransferase could not be demonstrated in this bacterium.
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PMID:Nitrogen assimilation in Rhodopseudomonas acidophila. 3 Nov 45

The activity of enzymes of glycine and alanine synthesis (glutamate-pyruvate aminotransferase, aspartate-beta-decarboxylase, threonine aldolase, serine hydroxymethyltransferase, alanine-glyoxylate aminotransferase, aspartate aminotransferase) is studied in haemolymph, fat body, fibroin and sericine divisions of silk gland of silkworm Bombyx mori at terminal period of larva development. Alanine-glyoxylate aminotransferase activity in fibroin division of silk gland (34,6 mu mole of glycine/mg of protein/min-10(-3)), alanine aminotransferase--in sericine division (36,0 mu mole of alanine/mg of protein/min-10(-3)) aspartate aminotransferase 27,3 mu mole of glutamic acid/mg of protein/min-10(-3)) and alanine aminotransferase (35,8 mu mole of alanine/mg of protein/min-10(-3)) on fat body. The ratio of alanine-glyoxylate aminotransferase/glutamate-pyruvate aminotransferase activities in posterior division of silk gland is near to glycine/alanine ratio in silk fibroin. The character of the enzymes activity in silkworm tissues correlates with the silk formation rate.
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PMID:[Glycine and alanine synthesis enzymes in the tissues of the silkworm during its development]. 99 78

We have synthesized and sequenced alanine:glyoxylate aminotransferase (AGT; HGMW-approved symbol for the gene--AGXT) cDNA from the liver of a primary hyperoxaluria type 1 (PH1) patient who had normal levels of hepatic peroxisomal immunoreactive AGT protein, but no AGT catalytic activity. This revealed the presence of a single point mutation (G----A at cDNA nucleotide 367), which is predicted to cause a glycine-to-glutamate substitution at residue 82 of the AGT protein. This mutation is located in exon 2 of the AGT gene and leads to the loss of an AvaI restriction site. Exon 2-specific PCR followed by AvaI digestion showed that this patient was homozygous for this mutation. In addition, three other PH1 patients, one related to and two unrelated to, but with enzymological phenotype similar to that of the first patient, were also shown to be homozygous for the mutation. However, one other phenotypically similar PH1 patient was shown to lack this mutation. The mechanism by which the glycine-to-glutamate substitution at residue 82 causes loss of catalytic activity remains to be resolved. However, the protein sequence in this region is highly conserved between different mammals, and the substitution at residue 82 is predicted to cause significant local structural alterations.
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PMID:A glycine-to-glutamate substitution abolishes alanine:glyoxylate aminotransferase catalytic activity in a subset of patients with primary hyperoxaluria type 1. 134 75

A deficiency of activity of the peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT,EC 2.6.1.44)has been found in the livers of six patients with primary hyperoxaluria type 1 (PH), including three in whom the tissue was obtained by percutaneous needle biopsy. AGT activity, assayed in unfractionated liver tissue, ranged from 11 to 47% of the mean control value, and appeared to be related to the clinical severity of PH and to several biochemical variables which indicate the degree of pathophysiological derangement. There was no difference between patients and controls in the activities of glutamate: glyoxylate aminotransferase (GGT, EC 2.6.1.4) or catalase (EC 1.11.1.6). In the five most severe cases residual AGT activity could be largely accounted for by the crossover from another enzyme, presumably GGT. PH can be diagnosed using percutaneous hepatic needle biopsy and assay of AGT, whose activity may be useful in determining the prognosis and likely severity of the disease.
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PMID:Enzymological diagnosis of primary hyperoxaluria type 1 by measurement of hepatic alanine: glyoxylate aminotransferase activity. 288 Jan 11

1. The distribution of L-alanine:glyoxylate aminotransferase (AGT) activities were found in Suncus liver, 55% in particulate fraction and 45% in supernatant. 2. 65% of AGT activities in particulate were dependent on AGT isoenzyme 2 (AGT 2) having molecular weight 210,000, the remainder (35%) of AGT activities were dependent on AGT isoenzyme 1 (AGT 1) which have aminotransferase activity for serine. AGT activities in supernatant were dependent on AGT 1, AGT 2 and alanine:2-oxoglutarate aminotransferase (GPT), and their activity ratios were 10, 15 and 75%, respectively. 3. Km values for alanine were 0.52 mM; AGT 1, 3.3 mM; AGT 2, 0.88 mM; GPT measuring with AGT activity. AGT activity of GPT was inhibited by addition of glutamate and its Ki value was 1.8 mM. 4. Some other properties of AGT 1, AGT 2 and GPT are described.
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PMID:Alanine:glyoxylate aminotransferase activities in liver of Suncus murinus (insectivora). 290 70

1. The activity of alanine:glyoxylate aminotransferase (AGT; EC 2.6.1.44) has been measured in the unfractionated livers of 20 patients with primary hyperoxaluria type 1 (PH1), three patients with other forms of primary hyperoxaluria and one PH1 heterozygote. The subcellular distribution of AGT activity was examined in four of the PH1 livers and in the liver of the PH1 heterozygote. 2. The mean AGT activity in the unfractionated PH1 livers was 12.6% of the mean control value. The activities of other aminotransferases and the peroxisomal marker enzymes were normal. When corrected for cross-over from glutamate:glyoxylate aminotransferase (GGT; EC 2.6.1.4), the mean AGT activity in the PH1 livers was reduced to 3.3% of the control values. 3. The livers from a patient with primary hyperoxaluria type 2 (D-glycerate dehydrogenase deficiency) and one with an undefined form of primary hyperoxaluria (possibly oxalate hyperabsorption) had normal AGT levels. The livers of a very mild PH1-type variant and a PH1 heterozygote had intermediate levels of AGT activity. 4. Subcellular fractionation of four PH1 livers by sucrose gradient isopycnic centrifugation demonstrated a complete absence of peroxisomal AGT activity. The subcellular distribution of the residual AGT activity was very similar to that of GGT activity (i.e. mainly cytosolic with a small amount mitochondrial). There were no alterations in the subcellular distributions of any of the peroxisomal marker enzymes. The subcellular distribution of AGT activity in the PH1 heterozygote liver was similar to that of the control (i.e. mainly peroxisomal).
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PMID:Further studies on the activity and subcellular distribution of alanine:glyoxylate aminotransferase in the livers of patients with primary hyperoxaluria type 1. 341 63

We have developed a sensitive assay for the measurement of alanine:glyoxylate aminotransferase (EC 2.6.1.44) activity in human liver. The assay is partly automated, and takes into consideration the sensitivity of the reaction to pH and to glyoxylate concentration. It is less subject to interference from other enzymes utilizing glyoxylate and to chemical interference from glyoxylate itself and can therefore be used without correction for cross-over by glutamate:glyoxylate aminotranferase (EC 2.6.1.4). The assay allows clear discrimination between normal and affected livers and is sufficiently sensitive to measure enzyme activity in fetal liver samples. Enzyme activity ranged from 17.9 to 38.5 mumol/h/mg protein in control livers (n = 9) and 0.8 to 9.5 mumol/h/mg protein in 30 of 39 hyperoxaluric patients studied. Normal alanine:glyoxylate aminotransferase activity (from 22.8 to 45.5 mumol/h/mg protein) allowed exclusion of primary hyperoxaluria type 1 in the other nine hyperoxaluric patients.
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PMID:A semiautomated alanine:glyoxylate aminotransferase assay for the tissue diagnosis of primary hyperoxaluria type 1. 924 73

Four alanine aminotransferases (AlaATs) are expressed in Medicago truncatula. In adult plants, two genes encoding mitochondrial isoforms m-AlaAT and alanine-glyoxylate aminotransferase (AGT), catalysing, respectively, reversible reactions of alanine/oxoglutarate<==>glutamate/pyruvate and alanine/glyoxylate<==>glycine/pyruvate, were expressed in roots, stems, and leaves. A gene encoding a cytosolic (c-AlaAT) isoform, catalysing the same reaction as m-AlaAT, was expressed specifically in leaves, while a gene encoding an isoform involved in branched chain amino acid metabolism was expressed in stems and roots. In young seedlings, only m-AlaAT and AGT were expressed in embryo axes. In hypoxic embryo axes, the amounts of transcript and putative protein of m-AlaAT (EC 2.6.1.2) increased while those of AGT (EC 2.6.1.44) decreased and in vivo enzyme activities changed as revealed by [(15)N]alanine and [(15)N]glutamate labelling. Under hypoxia, m-AlaAT catalysed only alanine synthesis while glutamate synthesis using alanine as amino donor was inhibited. As a result, alanine accumulated as the major amino acid in hypoxic seedlings instead of asparagine, in agreement with the involvement of the fermentative AlaAT pathway in hypoxia tolerance. Regulation of m-AlaAT at both the transcriptional and post-translational levels allowed for an increase in gene expression and orientation of the activity of the product of its transcription towards alanine synthesis under hypoxia. Labelling experiments showed that glycine synthesis occurred at the expense of either alanine or glutamate as amino donor, indicating that a glutamate-glyoxylate aminotransferase was operating together with AGT in Medicago truncatula seedlings. Both enzymes seemed to be inhibited by hypoxia, resulting in a very low amount of glycine in hypoxic seedlings.
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PMID:Characterization of alanine aminotransferase (AlaAT) multigene family and hypoxic response in young seedlings of the model legume Medicago truncatula. 1689 23

PH1 (primary hyperoxaluria type 1) is a severe inborn disorder of glyoxylate metabolism caused by a functional deficiency of the peroxisomal enzyme AGXT (alanine-glyoxylate aminotransferase), which converts glyoxylate into glycine using L-alanine as the amino-group donor. Even though pre-genomic studies indicate that other human transaminases can convert glyoxylate into glycine, in PH1 patients these enzymes are apparently unable to compensate for the lack of AGXT, perhaps due to their limited levels of expression, their localization in an inappropriate cell compartment or the scarcity of the required amino-group donor. In the present paper, we describe the cloning of eight human cytosolic aminotransferases, their recombinant expression as His6-tagged proteins and a comparative study on their ability to transaminate glyoxylate, using any standard amino acid as an amino-group donor. To selectively quantify the glycine formed, we have developed and validated an assay based on bacterial GO (glycine oxidase); this assay allows the detection of enzymes that produce glycine by transamination in the presence of mixtures of potential amino-group donors and without separation of the product from the substrates. We show that among the eight enzymes tested, only GPT (alanine transaminase) and PSAT1 (phosphoserine aminotransferase 1) can transaminate glyoxylate with good efficiency, using L-glutamate (and, for GPT, also L-alanine) as the best amino-group donor. These findings confirm that glyoxylate transamination can occur in the cytosol, in direct competition with the conversion of glyoxylate into oxalate. The potential implications for the treatment of primary hyperoxaluria are discussed.
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PMID:Recombinant production of eight human cytosolic aminotransferases and assessment of their potential involvement in glyoxylate metabolism. 1954 38

The metabolism of 2-13C/15N-glycine and U-13C-glucose was determined in four tissue blocks (adductor muscle, stomach and digestive gland, mantle, and gills) of the Eastern oyster (Crassostrea virginica) using proton (1H) and carbon-13 (13C) nuclear magnetic resonance (NMR) spectroscopy. The oysters were treated in aerated seawater with three treatments (5.5 mM U-13C-glucose, 2.7 mM 2-13C/15N-glycine, and 5.5 mM U-13C-glucose plus 2.7 mM 2-13C/15N-glycine) and the relative mass balance and 13C fractional enrichments were determined in the four tissue blocks. In all tissues, glycine was metabolized by the glycine cycle forming serine exclusively in the mitochondria by the glycine cleavage system forming 2,3-13C-serine. In muscle, a minor amount of serine-derived pyruvate entered the Krebs cycle as substantiated by detection of a trace of 2,3-13C-aspartate. In all tissues, U-13C-glucose formed glycogen by glycogen synthesis, alanine by glycolysis, and glutamate and aspartate through the Krebs cycle. Alanine was formed exclusively from glucose via alanine transaminase and not glycine via alanine-glyoxylate transaminase. Based on isotopomer analysis, pyruvate carboxylase and pyruvate dehydrogenase appeared to be equal points for pyruvate entry into the Krebs cycle. In the 5.5 mM U-13C-glucose plus 2.7 mM 2-13C/15N-glycine emergence treatment used to simulate 12 h of "low tide", oysters accumulated more 13C-labeled metabolites, including both anaerobic glycolytic and aerobic Krebs cycle intermediates. The aerobic metabolites could be the biochemical result of the gaping behavior of mollusks during emergence. The change in tissue distribution and mass balance of 13C-labeled nutrients (U-13C-glucose and 2-13C/15N-glycine) provides the basis for a new quantitative fluxomic method for elucidating sub-lethal environmental effects in marine organisms called whole body mass balance phenotyping (WoMBaP).
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PMID:Fluxomics of the eastern oyster for environmental stress studies. 2495 87


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