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

It has previously been demonstrated that accumulated beta-catenin serves as an oncoprotein in synovial sarcoma and results in a poor overall survival rate, but the frequency of beta-catenin mutation was quite low (8.2%). The present study, using essentially the same study group of cases, screened for genetic alterations in the mutation cluster region (MCR) of the APC gene in 49 cases of synovial sarcoma. SSCP analysis followed by DNA direct sequencing revealed five missense APC mutations in four cases of synovial sarcoma (8.2%). The mutational sites comprised one case each at codons 1299 (GCT to ACT, Ala to Thr), 1412 (GGA to AGA, Gly to Arg), and 1414 (GTA to ATA, Val to Ile), in addition to one case with double point mutations at codon 1398 (AGT to AAT, Ser to Asn) and at codon 1413 (ATG to ATA, Met to Ile), together with beta-catenin mutation at codon 32 (GAC to TAC, Asp to Tyr). All four cases with APC mutations were histologically of the monophasic fibrous type and showed beta-catenin accumulation. All three cases with APC mutations available for follow-up data were long survivors. This study provides the first evidence that APC mutations also occur in the field of sarcoma, especially in synovial sarcoma.
...
PMID:APC mutations in synovial sarcoma. 1192 Jul 41

We report on a 15-year-old girl who presented with pituitary hypoplasia, os odontoideum, renal dysplasia, an asymmetrically short right leg, and postaxial hypodactyly of the right foot. Her endocrinological data showed anterior pituitary hormone deficiency. The fact that she had healthy parents and an elder sister suggests that she had either a de novo mutation or autosomal recessive inheritance. We speculated that bone morphogenetic protein 4 (BMP4), BMP2, or pituitary homeobox 1 (PTX1) might be the responsible genes in this patient based on the similarity of her clinical symptoms and phenotypes to knock-out mice of these genes. We performed mutation analysis of these genes by direct sequencing of genomic DNA. In BMP2 gene, AGA right curved arrow AGT transversion in exon 3, converting arginine to serine was detected. In PTX1 gene, transversion of GCC right curved arrow GGC in exon 2, converting alanine to glycine at codon 184 was found in the patient and controls. We did not find any non-sense mutations although 5 polymorphisms of these genes were found. This constellation of findings may represent a new entity of congenital combined pituitary hormone deficiency.
...
PMID:Lack of aberrations of the BMP4, BMP2, and PTX1 genes in a patient with pituitary hypoplasia, os odontoideum, renal dysplasia, and right leg anomalies. 1216 3

This study describes the comparative analysis of two insect recombinant aminotransferases, Aedes aegypti 3-hydroxykynurenine (3-HK) transaminase/alanine glyoxylate aminotransferase (Ae-HKT/AGT) and Drosophila melanogaster serine pyruvate aminotransferase (Dm-Spat), which share 52% identity in their amino acid sequences. Both enzymes showed AGT activity. In addition, Ae-HKT/AGT is also able to catalyze the transamination of 3-HK or kynurenine with glyoxylate, pyruvate or oxaloacetate as the amino acceptor. Kinetic analysis and other data suggest that Ae-HKT/AGT plays a critical role in mosquito tryptophan catabolism by detoxifying 3-HK and that Dm-Spat is primarily involved in glyoxylate detoxification.
...
PMID:Comparative characterization of Aedes 3-hydroxykynurenine transaminase/alanine glyoxylate transaminase and Drosophila serine pyruvate aminotransferase. 1222 Jun 60

The aim of this study was to identify K-ras mutations as marker for isolated tumor cells in liver, lymph node, and bone marrow specimens of colorectal cancer patients. To detect these, a PCR-RFLP assay was used with a sensitivity exceeding that of routine histopathology by at least 1 order of magnitude. In addition, the ratio of mutated versus wild-type alleles was determined by an internal standard. Of 199 patients, 74 (37.5%) were found to bear a K-ras-positive tumor. Of these, 60 (81%) were mutated in codon 12 and 14 (19%) in codon 13 (P < 0.001). In addition, 14 organs were found K-ras positive, 13 of which were from 12 patients with a K-ras-positive tumor (16%) and 1 from a patient with a K-ras-negative tumor (0.8%). Eight patients exhibited liver involvement and 6 showed lymph node involvement. Remarkably, no bone marrow specimen was found K-ras positive (P < 0.017 versus liver involvement). Sequence analysis of tumor DNA revealed that GGT (Gly) was replaced by GAT (Asp; 35%), GTT (Val; 32%), AGT (Ser; 13%), GCT (Ala; 10%), TGT (Cys; 8%), and CGT (Arg; 2%) for codon 12, and by GAC (Asp) as the only type of mutation for codon 13. In colorectal carcinomas the ratio of K-ras mutated versus wild-type alleles ranged over 4 orders of magnitude (10(0)-10(-4), median: 10(-2)) and was correlated with both, residual tumor load (R1/2; P = 0.028) and distant metastasis (M1; P = 0.057). These results show that detection of K-ras mutated alleles by PCR-RFLP in patients with colorectal carcinoma may aid in the identification of isolated tumor cells. High ratios of K-ras alleles were correlated with certain negative prognostic parameters (R,M). In accord with its function as a primary filter for colorectal carcinoma cells, the liver was more often contaminated with K-ras-positive cells than bone marrow.
...
PMID:Detection of isolated tumor cells by polymerase chain reaction-restriction fragment length polymorphism for K-ras mutations in tissue samples of 199 colorectal cancer patients. 1476 87

In the mosquito, transamination of 3-HK (3-hydroxykynurenine) to XA (xanthurenic acid) is catalysed by an AGT (alanine glyoxylate aminotransferase) and is the major branch pathway of tryptophan metabolism. Interestingly, malaria parasites hijack this pathway to use XA as a chemical signal for development in the mosquito. Here, we report that the mosquito has two AGT isoenzymes. One is the previously cloned AeHKT [Aedes aegypti HKT (3-HK transaminase)] [Han, Fang and Li (2002) J. Biol. Chem. 277, 15781-15787], similar to hAGT (human AGT), which primarily catalyses 3-HK to XA in mosquitoes, and the other is a typical dipteran insect AGT. We cloned the second AGT from Ae. aegypti mosquitoes [AeAGT (Ae. aegypti AGT)], overexpressed the enzyme in baculovirus/insect cells and determined its biochemical characteristics. We also expressed hAGT for a comparative study. The new cloned AeAGT is highly substrate-specific when compared with hAGT and the previously reported AeHKT and Drosophila AGT, and is translated mainly in pupae and adults, which contrasts with AeHKT that is expressed primarily in larvae. Our results suggest that the physiological requirements of mosquitoes and the interaction between the mosquito and its host appear to be the driving force in mosquito AGT evolution.
...
PMID:Evolution of two alanine glyoxylate aminotransferases in mosquito. 1668 62

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.
...
PMID:Characterization of alanine aminotransferase (AlaAT) multigene family and hypoxic response in young seedlings of the model legume Medicago truncatula. 1689 23

Human hepatic peroxisomal AGT (alanine:glyoxylate aminotransferase) is a PLP (pyridoxal 5'-phosphate)-dependent enzyme whose deficiency causes primary hyperoxaluria Type I, a rare autosomal recessive disorder. To acquire experimental evidence for the physiological function of AGT, the K(eq),(overall) of the reaction, the steady-state kinetic parameters of the forward and reverse reactions, and the pre-steady-state kinetics of the half-reactions of the PLP form of AGT with L-alanine or glycine and the PMP (pyridoxamine 5'-phosphate) form with pyruvate or glyoxylate have been measured. The results indicate that the enzyme is highly specific for catalysing glyoxylate to glycine processing, thereby playing a key role in glyoxylate detoxification. Analysis of the reaction course also reveals that PMP remains bound to the enzyme during the catalytic cycle and that the AGT-PMP complex displays a reactivity towards oxo acids higher than that of apoAGT in the presence of PMP. These findings are tentatively related to possible subtle rearrangements at the active site also indicated by the putative binding mode of catalytic intermediates. Additionally, the catalytic and spectroscopic features of the naturally occurring G82E variant have been analysed. Although, like the wild-type, the G82E variant is able to bind 2 mol PLP/dimer, it exhibits a significant reduced affinity for PLP and even more for PMP compared with wild-type, and an altered conformational state of the bound PLP. The striking molecular defect of the mutant, consisting in the dramatic decrease of the overall catalytic activity (approximately 0.1% of that of normal AGT), appears to be related to the inability to undergo an efficient transaldimination of the PLP form of the enzyme with amino acids as well as an efficient conversion of AGT-PMP into AGT-PLP. Overall, careful biochemical analyses have allowed elucidation of the mechanism of action of AGT and the way in which the disease causing G82E mutation affects it.
...
PMID:Human wild-type alanine:glyoxylate aminotransferase and its naturally occurring G82E variant: functional properties and physiological implications. 1769 73

With the aim to investigate association of polymorphisms of candidate genes with clinical peculiarities of hypertensive disease in patients having burdened familial anamnesis we examined 413 (229 men and 184 women, mean age 60.3 +/- 0.59 years) patients with essential arterial hypertension (AH). Determination of alleles and genotypes of polymorphic markers of ACE, AGT, AT2R1, CYP11B2, NOS3, ENDl, GNB3, PPARA, PPARG2, MTHFR, CAT, SOD2, PON1, PON2 sigma APOB, APOE, LPL genes was carried out with the use of polymerase chain reaction. Patient with AH having hereditary load were younger (58.9 +/- 0.75 and 61.3 +/- 0.89 years, respectively, p=0.017) and had significantly lower age of debut of the disease (44.4 +/- 0.84 and 47.5 +/- 1.03 years, respectively; p=0.013), higher values of systolic (204.8 +/- 7.66 and 187.0 +/- 2.04 mm Hg; p=0.032) and diastolic (111.2 +/- 1.05 and 107.3 +/- 1.17 mm Hg, respectively; p=0.025) arterial pressure (AP) compared with patients with AH without hereditary loaded anamnesis. Portion of patients with 3 degree of severity of AH was higher among patients with "familial" AH (53.6 and 44.1%, respectively, p=0.018). Early debut (in the age younger than 45 years in men and 55 years in women) was associated with carriage of genotype TT of polymorphic marker C825 of GNB3 gene (OR 2.65 95CI [1.27-5.54], p=0.005) and genotype AA of polymorphic marker A(A153)G of AT2R1 gene (OR 1.67 95% CI [1.03-2.77], p=0.024). Higher AP level corresponding to 3-rd degree AH in the group of patients with burdened familial anamnesis was associated with carriage of Asn allele of polymorphic marker Lysl98Asn of EDN1 gene (OR 2.24 95% CI [1.20-4.18], p=0.008), 4a allele of polymorphic marker 4a/4b of NOS3 gene (OR 2.23 C/[1.29-3.83], p=0.002), genotype ArgArg of polymorphic marker Glnl92Arg of PON1 gene (OR 6.14 C7[1.46-25.67], p=0.01), T allele of polymorphic marker of C825T gene GNB3 (OR 1.75 C/[1.11-2.76], p=0.01) and genotype AA of polymorphic marker A(A153)G of AT2R1 gene (OR 2.61 C/11.29-5.34], p=0.005). In patients without burdened familial anamnesis 3-rd degree AH was associated with higher frequency of allele Ala of polymorphic marker Pro12A1a of PPARG2 gene.
...
PMID:[Association of genetic factors with clinical peculiarities of hypertensive disease in patients with burdened familial anamnesis]. 1925 15

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.
...
PMID:Recombinant production of eight human cytosolic aminotransferases and assessment of their potential involvement in glyoxylate metabolism. 1954 38

Urinary excretion of oxalate is one of risk factors in urinary stone formation. Prevention of undesirable overflow into the production of oxalate definitely leads to a decrease of urolithiasis. The activity of serine : pyruvate/alanine : glyoxylate aminotransferase (SPT/AGT) or glyoxylate reductase/hydroxypyruvate reductase (GRHPR), the key enzyme of primary hyperoxlauria type 1 and 2, respectively, and their subcellular distribution highly affects the oxalate production. On the other hand, urolithiasis is tightly related to lifestyle disease, such as diabetes mellitus and insulin resistance. The hypothesis that insulin resistance induces mitochondria dysfunction, resulting in the decrease of mitochondria-related enzyme activity is a very attractive new treatment strategy of urolithiasis. Namely, the improvement of insulin resistance might prevent stone formation.
...
PMID:[Future perspective in the treatment of urolithiasis based on oxalate metabolism]. 2130 60


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

---