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)

Isocitrate lyase (EC 4.1.3.1) and malate synthase (EC 4.1.3.2), the two enzymes characteristic of the glyoxylate cycle, were demonstrated in promastigotes of five species of Leishmania (L. brasiliensis, L. donovani, L. mexicana, L. tarentolae, and L. tropica). Both enzymes were present in cells grown in a medium containing 10 mM glucose. Substitution of glucose with 20 mM acetate did not enhance enzyme levels. Acetate was readily taken up and metabolized by the cells. The distribution of label from acetate into various intermediary metabolites indicates a functional glyoxylate cycle and its role in gluconeogenesis/glyconeogenesis. The glyoxylate cycle in conjunction with alanine-glyoxylate aminotransferase and glyoxylate-aspartate aminotransferase could also be important in providing glyoxylate, the precursor for glycine biosynthesis.
...
PMID:Evidence for a functional glyoxylate cycle in the leishmaniae. 69 79

We followed patients with pregnancy and diabetes in an outpatient clinic. 240 had gestational diabetes, 16 had type II and 5 type I diabetes. 85% of 110 patients with gestational diabetes had normal glucose tolerance test post partum (AGT). Type I patients were younger (25 years old) than AGT (32) or type II (33) patients. Complications frequently observed among diabetics included hypertension, premature membrane rupture and polyhydroamnios (the latter only among AGT and type II patients). Insulin was required for diabetes control in 14% of cases. Cesarean section was more frequent in diabetics than in a control population (21%): AGT 45%, type II 45% and type I 60%. Larger newborns occurred in 21% of AGT and 22% of type II as compared to 6% in controls. Neonatal mortality was 2.1% in AGT patients (0.8% in controls). Hyperbilirrubinemia, polyglobulia and hypocalcemia were more frequent among newborns of diabetic patients.
...
PMID:[Clinical experience in diabetes and pregnancy]. 251 61

Glycated plasma proteins (GPP) and glycated hemoglobin (G Hb) has been evaluated in 134 non-diabetics (ND), 299 women with potential abnormality of glucose tolerance (pot.AGT), 75 with impaired glucose tolerance (IGT) and 34 insulin dependent diabetics (IDDM) during pregnancy or postpartum including 94 cord blood determinations. Mean HbA1c levels were significantly elevated in IDDM (6.6 +/- 1.3% M +/- SD) compared to ND (5.1 +/- 0.7%; P less than 0.01), but were similar for the other groups studied. Mean GPP were increased for the IDDM (0.58 +/- 0.29 nmol 5- HMF/mg protein; M +/- SD) and the IGT-group (0.53 +/- 0.22) over ND (0.3 +/- 0.13; P less than 0.01) and the Pot.AGT group (0.37 +/- 0.14; P less than 0.01). 6% of the ND, 15% of the Pot AGT-, 52% of the IGT- and 62% of the IDDM group were found to have GPP values exceeding the 97% confidential limit of the ND. However, the large overlap of individual values from patients with different degrees of glucose intolerance with the normal range of pregnancy precludes the use of GPP as a screening parameter for IGT during pregnancy. A 30-35% reduction of fetal hemoglobin- and plasma protein glycosylation relative to maternal values was observed.
...
PMID:Glycated plasma proteins in normal and diabetic mothers and their offsprings. 346 46

Alanine: glyoxylate aminotransferase (EC 2.6.1.44), which is involved in the glyoxylate pathway of glycine and serine biosynthesis from tricarboxylic acid-cycle intermediates in Saccharomyces cerevisiae, was highly purified and characterized. The enzyme had Mr about 80 000, with two identical subunits. It was highly specific for L-alanine and glyoxylate and contained pyridoxal 5'-phosphate as cofactor. The apparent Km values were 2.1 mM and 0.7 mM for L-alanine and glyoxylate respectively. The activity was low (10 nmol/min per mg of protein) with glucose as sole carbon source, but was remarkably high with ethanol or acetate as carbon source (930 and 430 nmol/min per mg respectively). The transamination of glyoxylate is mainly catalysed by this enzyme in ethanol-grown cells. When glucose-grown cells were incubated in medium containing ethanol as sole carbon source, the activity markedly increased, and the increase was completely blocked by cycloheximide, suggesting that the enzyme is synthesized de novo during the incubation period. Similarity in the amino acid composition was observed, but immunological cross-reactivity was not observed among alanine: glyoxylate aminotransferases from yeast and vertebrate liver.
...
PMID:Characteristics of alanine: glyoxylate aminotransferase from Saccharomyces cerevisiae, a regulatory enzyme in the glyoxylate pathway of glycine and serine biosynthesis from tricarboxylic acid-cycle intermediates. 393 86

1. In rats, liver 4-hydroxy-2-oxoglutarate aldolase and hydroxyproline oxidase activities are maximal in the suckling period. 2. Liver activities for 4-hydroxy-2-oxoglutarate aldolase, alanine-glyoxylate aminotransferase, serine-pyruvate aminotransferase and serine dehydratase, but not hydroxyproline oxidase, are increased in rats on a high-fat, carbohydrate-free diet. 3. It is suggested that 4-hydroxy-2-oxoglutarate may be a significant source of glyoxylate for glycine and hence glucose formation. 4. Mammalian liver hydroxyproline oxidase activity is higher in carnivorous species; necessary, perhaps, to metabolise a relatively large influx of hydroxyproline on a flesh diet.
...
PMID:Comparative and developmental studies on 4-hydroxy-2-oxoglutarate aldolase and hydroxyproline oxidase. 708 20

A subset of human growth hormone (GH)-secreting pituitary tumors contains the gsp oncogene that encodes an activation mutation of the alpha-subunit of the stimulatory GTP-binding protein (G(S) alpha). This study was undertaken to investigate the frequency of the gsp oncogene in GH-secreting pituitary tumors in Korean acromegalic patients and to elucidate the clinical characteristics of these patients to endocrine testing. Direct polymerase chain reaction sequencing revealed the gsp oncogene mutation in 9 out of 21 tumors (43%) at amino acid 201 of the G(S) alpha protein. A single nucleotide mutation in the tumors carrying the gsp oncogene was observed, which replaced an arginine (CGT) in the normal protein with cysteine (TGT) in eight tumors and serine (AGT) in one tumor. The patients with the gsp oncogene mutation (group 1) were older (54 +/- 10 vs 41 +/- 11 years, p = 0.0085) than those without the mutation (group 2). Sex, tumor size and grade, basal GH and prolactin levels, the GH response to oral glucose loading, the GH fluctuation and the paradoxical response to thyrotropin-releasing hormone or gonadotropin-releasing hormone did not differ between the groups. The gsp oncogene was found mostly in somatotroph adenomas. The octreotide-induced GH suppression was significantly higher in group 1 than in group 2 (95 +/- 5% vs 81 +/- 17%, p = 0.0335). The GH response to bromocriptine did not differ between the groups. These results suggest that the G(S) alpha mutations of GH-secreting tumor are observed in Korean acromegalic patients with similar frequency to those of western countries. The patients with gsp oncogene are likely to be older than those without the oncogene, and show excellent response of GH suppression to octreotide.
...
PMID:Characteristics of gsp-positive growth hormone-secreting pituitary tumors in Korean acromegalic patients. 876 42

The Keewatin Inuit of the Northwest Territories of Canada have a very low age-adjusted mortality rate from coronary heart disease. We hypothesized that this apparent protection from disease has a genetic basis. We determined the prevalence of the disease-associated alleles of five candidate genes for atherosclerosis-related phenotypes. Surprisingly, four of the five alleles studied, namely AGT T235, FABP2 T54, PON R192 and APOE E4, were significantly more frequent in a sample of 175 Keewatin Inuit than among a representative control sample of whites living in the region. The high frequencies of these disease-associated alleles suggests either that they have no relationship with disease susceptibility in the Inuit, or that some unmeasured genetic and/or environmental factors mitigate disease susceptibility that is associated with these alleles. This highlights the difficulty in extrapolating findings from one population to another. Also, very modest genotype-phenotype associations were observed between APOE genotype (P = 0.016) and plasma low-density lipoprotein cholesterol concentration and between FABP2 genotype and plasma 2-h postprandial, glucose concentration (P = 0.048). The relationship between APOE alleles and plasma low-density lipoprotein cholesterol was the same as has been previously reported in many study samples. However, the relationship between FABP2 alleles and plasma 2-h postprandial glucose concentrations was the opposite to that reported in other studies. This suggests that differences in environment, such as the type of fatty acid consumed, interacts with functional differences in gene products involved in candidate metabolic pathways to produce phenotypic differences.
...
PMID:Are Canadian Inuit at increased genetic risk for coronary heart disease? 918 78

Alignment of amino acids of the region implicated in glucose binding from a series of hexokinases showed that Schizosaccharomyces pombe hexokinase 1 had a Ser residue in a place where all other kinases had an Asn. We changed an AGT codon to AAT to place an Asn in the Ser213 position. This mutation decreased Km for glucose from 9.4 mM to 1.6 mM and the ratio Vmax (Fructose)/Vmax (Glucose) from 5 to 2.5. Also the Km for 2-deoxyglucose decreased from 2.7 mM to 0.8 mM. A mutation in the similar position of S. pombe hexokinase 2 (Asn196/Ser) increased the Km for glucose from 0.16 mM to 0.56 mM. Fermentation of glucose is not detectable in a S. pombe mutant with only hexokinase 1 activity but expression of the hxk1(S213/N) gene conferred ability to ferment the sugar. While the mutated hexokinase 1 partially mimicked S. cerevisiae hexokinase II in catabolite repression of invertase, the wild type one could not substitute for it.
...
PMID:A mutation Ser213/Asn in the hexokinase 1 from Schizosaccharomyces pombe increases its affinity for glucose. 979 Sep 75

Plasmodium falciparum infection kills more than 1 million children annually. Novel drug targets are urgently being sought as multidrug resistance limits the range of treatment options for this protozoan pathogen. PfHT1, the major hexose transporter of P. falciparum is a promising new target. We report detailed structure-function studies on PfHT1 using site-directed mutagenesis approaches on residues located in helix V (Q169N) and helix VII ((302)SGL --> AGT). Studies with hexose analogues in these mutants have established that hexose recognition and permeation are intimately linked to these helices. A "fructose filter" effect results from the Q169N mutation (abolishing fructose uptake but preserving affinity and transport of glucose, as reported in Woodrow, C. J., Burchmore, R. J. S., and Krishna, S. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 9931-9936). Associated changes in competition for glucose uptake by C-2, C-3, and C-6 glucose analogues compared with native PfHT1 indicate subtle alterations in substrate interaction in this mutant. The K(m) values for glucose uptake in helix VII mutants are also similar to native PfHT1. Hydrogen bonding to positions C-5 and C-6 in glucose analogues becomes relatively more important in these mutants compared with native PfHT1. To increase understanding of hexose permeation pathways in PfHT1, we have developed the first three-dimensional model for PfHT1. As predicted for GLUT1, the principal mammalian glucose transporter, PfHT1 contains a main and an auxiliary channel. After modeling, the Q169N mutation leads predominantly to local structural changes, including displacement of neighboring helix IV. The (302)SGL position in helix VII lies in the same plane as Gln-169 in helix V but is also adjacent to the main hexose permeation pathway, consistent with results from experiments mutating this triplet motif. Furthermore, there are obvious structural and functional differences between GLUT1 and PfHT1 that can now be explored in detail using the approaches presented here. The development of specific inhibitors for PfHT1 will also be aided by these insights.
...
PMID:Mutational analysis of the hexose transporter of Plasmodium falciparum and development of a three-dimensional model. 1204 21

Postprandial hyperglycemia has been shown to increase the risk of cardiovascular disease as much as overt diabetes mellitus does. The aim of this study was to determine whether isolated post-challenge hyperglycemia during an oral glucose tolerance test (OGTT) is related to exaggerated neointimal proliferation after coronary stent implantation. Forty seven coronary lesions treated with stents in 40 patients who had normal fasting glucose levels (<110 mg/dl) were categorized into the following 2 groups according to the results of a 75-g OGTT: 29 lesions in 24 patients with normal glucose tolerance (NGT group) and 18 lesions in 16 patients with abnormal glucose tolerance (AGT group). Although there were no differences in angiographic characteristics before and immediately after stenting between the 2 groups, the minimal lumen diameter was significantly smaller (p=0.04) and the degree of stenosis and late loss were also significantly greater (p=0.01 and p=0.047) in the AGT group than in the NGT group at 6-month follow-up. Multiple regression analysis including the insulin concentrations during an OGTT revealed that the 120-min plasma glucose concentration after glucose load significantly correlated with late loss (p=0.0018) and the degree of stenosis (p=0.0100) at follow-up. It is concluded that isolated post-challenge hyperglycemia exaggerates neointimal hyperplasia after coronary stent implantation.
...
PMID:Isolated post-challenge hyperglycemia in patients with normal fasting glucose concentration exaggerates neointimal hyperplasia after coronary stent implantation. 1252 Jan 54


1 2 3 Next >>

---