Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.2.1.13 (glyceraldehyde-3-phosphate dehydrogenase)
 6,511 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemical modification of one arginine residue per subunit of tetrameric D-glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12) molecule results in a 85-95% loss of its activity (Nagradova and Asryants (1975) Biochim. Biophys. Acta 386, 365-368; Nagradova, N.K., Asryants, R.A., Benkevich, N.V. and Safronova, M.I. (1976) FEBS Lett. 69, 246-248). Transient kinetic experiments performed in the present work with modified rabbit muscle and Baker's yeast enzymes showed that the first-order rate constant of acyl-enzyme.NADH formation was diminished 30-fold with the rabbit muscle enzyme and 60-fold with the Baker's yeast enzyme. Modification of arginine residues was shown also to affect the second step of the catalytic reaction, the phosphorolysis of the acyl-enzyme (the second-order rate constant of phosphorolysis decreased 9-fold in the case of the rabbit muscle enzyme and 40-fold in the case of the Baker's yeast enzyme). The native and modified enzymes exhibited similar inhibitory constant values with respect to NADH, suggesting no contribution of arginine residues to the acyl-enzyme.NADH complex destabilization. By and large, the experimental data are consistent with the hypothetical scheme proposed on the basis of X-ray crystallography studies to describe a participation of Arg-231 in the catalytic mechanism of D-glyceraldehyde-3-phosphate dehydrogenase (Grau (1982) in the Pyridine Nucleotide Coenzymes, p. 135-187).
 ...
PMID:An examination of the role of arginine residues in the functioning of D-glyceraldehyde-3-phosphate dehydrogenase. 266 76

An accelerated rate of glucose transport and catabolism is a common characteristic of cellular transformation. We have previously found elevated expression of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in human pancreatic and colonic adenocarcinomas (Schek et al.: Cancer Res 48:6354-6359, 1988). To investigate further the expression of this enzyme in the process of tumorigenesis, we examined GAPDH expression in a panel of oncogene-transformed fibroblasts. Significant elevations of GAPDH mRNA and glucose transporter protein mRNA levels were observed in ras- and mos-transformed NIH 3T3 cells, whereas little or no change was found in c-src-, v-src-, c-myc-, E1A-, v-fos-, and PKC-gamma-transfected cells. Furthermore, the level of GAPDH mRNA correlated with the transformed state in a series of ras-transformed and revertant cell lines. Immunoblot analysis confirmed that GAPDH polypeptide was significantly elevated in the cell lines with elevated mRNA levels. Cell cycle analysis data suggested that the effect on GAPDH expression correlated with oncogene expression rather than cell growth fraction. These results suggest that altered GAPDH gene expression occurs during some growth deregulated states, and this, along with increased glucose transporter (and possibly other glycolytic enzyme) expression, is likely to contribute to the increased metabolic capacity of cells in these states.
 ...
PMID:Increased expression of glycolysis-associated genes in oncogene-transformed and growth-accelerated states. 276 28

Glyceraldehyde-3-phosphate dehydrogenase [GAPDH; D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12] mRNA levels are induced by physiologic concentrations of insulin in cultured 3T3-F442A adipocyte and H35 hepatoma cell lines. To examine the mechanism by which insulin regulates GAPDH mRNA levels in these two insulin-sensitive tissues, we have isolated a functional human GAPDH gene. When stably transfected and expressed in 3T3-F442A preadipocytes and H35 hepatoma cells, the intact human GAPDH gene is induced 10-fold by insulin in 3T3-F442A adipocytes and 3-fold by insulin in H35 hepatoma lines, which is similar to the induction obtained with the endogenous gene. A human GAPDH-chloramphenicol acetyltransferase construct, containing sequences -487 to +20 of the human gene fused to the chloramphenicol acetyltransferase gene, is regulated by insulin in stably transfected 3T3 adipocytes and stably or transiently transfected H35 hepatoma cell lines, whereas the Rous sarcoma virus-chloramphenicol acetyltransferase fusion protein is not. Thus, the inductive effect of insulin on human GAPDH gene expression is mediated through cis-acting sequences located between -487 and +20 of the human GAPDH gene.
 ...
PMID:Insulin stimulates glyceraldehyde-3-phosphate dehydrogenase gene expression through cis-acting DNA sequences. 283 30

Incubation of rabbit muscle glyceraldehyde-3-phosphate dehydrogenase (GAPDH) with the antibiotic pentalenolactone (1) resulted in time-dependent, irreversible inhibition of GAPDH. The kinetics of inactivation were biphasic, exhibiting an initial rapid phase and a slower second phase. Pentalenolactone methyl ester (2) also irreversibly inactivated GADPH, albeit at a slower rate and with a higher KI. The substrate glyceraldehyde-3-phosphate (G-3-P) afforded protection against inactivation by 1, whereas the presence of NAD+ in the incubation mixture stimulated the inactivation by increasing the apparent affinity of the enzyme for the inhibitor. In steady-state kinetic experiments, 1 acted as a competitive inhibitor of GAPDH with respect to G-3-P but exhibited uncompetitive inhibition with respect to NAD+. Inactivation of NAD+-free apo-GAPDH by 1 showed simple pseudo-first-order kinetics. By titrating the free thiol residues of partially inactivated GAPDH, it was found that both pentalenolactone and pentalenolactone methyl ester react with all four Cys-SH residues of the tetrameric GAPDH.
 ...
PMID:Inhibition of glyceraldehyde-3-phosphate dehydrogenase by pentalenolactone: kinetic and mechanistic studies. 293 Jan 99

We have isolated and sequenced a full-length cDNA clone encoding rat glyceraldehyde-3-phosphate-dehydrogenase (GAPDH, E.C.1.2.1.12). The entire mRNA is 1269 nucleotides long exclusive of poly(A) and contains respectively 71 and 196 bases of 5' and 3' non-coding regions. Primer extension as well as S1 nuclease protection experiments clearly established that a single (or at least a highly prominent) GAPDH mRNA species is expressed in all rat tissues examined. This sequence allowed the determination of the hitherto unknown primary structure of rat GAPDH which is 333 aminoacids long. Comparison between GAPDH sequences from rat, man and chicken revealed a high degree of sequence conservation at both nucleotide and protein levels.
 ...
PMID:Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. 298 24

A protein kinase activity responsible for the in vitro phosphorylation of at least six endogenous polypeptides including the large subunit of the ribulose-1,5-bisphosphate carboxylase/oxygenase (EC 4.1.1.39) is present in the stroma (3000 X g supernatant, S30) of spinach chloroplasts. The phosphorylation of the ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit is strongly enhanced when sodium fluorure is used as a protein phosphatase inhibitor. Phosphorylation occurs on threonine and serine residues. The protein kinase involved is not Ca2+-dependent. There is also evidence for a protein phosphatase activity which suggests a coupled regulation by a phosphorylation-dephosphorylation process. The phosphorylating activity is drastically reduced when S30 is prepared from leaves harvested after a dark period. Phosphorylation of the ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit is not related to its own synthesis. The in vitro phosphorylation of the glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.13) is also demonstrated.
 ...
PMID:Phosphorylation in vitro of the large subunit of the ribulose-1,5-bisphosphate carboxylase and of the glyceraldehyde-3-phosphate dehydrogenase. 303 22

The mRNA products of four genes, carbonic anhydrase III (CAIII), fast myosin heavy chain (MHCf), actin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), were assayed by Northern and slot-blot analysis in rabbit tibialis anterior and extensor digitorum longus muscles that were subjected to electrical stimulation for periods of up to 21 days. Marked changes in mRNA levels were seen for all four genes. The mRNA for CAIII, which is specific for type 1 fibers, rose significantly, whereas the MHCf mRNA fell markedly in the stimulated muscles. Changes in GAPDH mRNA were consistent with a reduced dependence on anaerobic glycolysis as an energy source. Actin mRNA levels were noticeably depressed in the early stages of stimulation. Thus for several classes of muscle protein, the response to chronic low-frequency stimulation appears to involve changes at the level of gene transcription.
 ...
PMID:Changes in skeletal muscle gene transcription induced by chronic stimulation. 314 74

Glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.2.12) (GAPDH) mRNA levels, protein, and enzymatic activity increase in 3T3-F442A adipocytes after exposure to physiological concentrations of insulin (Alexander, M., Curtis, G., Avruch, J., and Goodman, H. (1985) J. Biol. Chem. 260, 11978-11985). In order to understand the mechanism of this regulation, we have isolated and sequenced 5.4 kilobase pairs of a 12-kilobase pair human genomic clone encoding a functional GAPDH gene. The gene consists of 9 exons and 8 introns with eukaryotic signals necessary for the transcription and translation of GAPDH mRNA. The exon sequence confirms previously published cDNA sequences for human GAPDH in muscle, liver, and erythrocytes. The organization of the human and the unique chicken GAPDH genes is strikingly similar. Although chicken exons VIII-XI have been fused into human exon 8, introns which separate exons encoding the NAD binding, catalytic, and helical domains of the GAPDH protein have been retained. Stable transfection of rodent cells with the intact human GAPDH gene resulted in the expression of a correctly initiated human GAPDH mRNA and an enzymatically active human GAPDH polypeptide. Thus, the gene contains a functional promoter and intact coding sequences. Although many processed GAPDH pseudogenes and GAPDH-like sequences are present in the human genome, Southern blot analysis of human genomic DNA using a probe derived from the 3'-untranslated region of the GAPDH gene detected only two genes, a 10-copy processed pseudogene and a single copy of the isolated gene. In contrast, a probe derived from an intron segment of the isolated gene detected only a single copy of the GAPDH gene. Collectively, these findings strongly suggest that the human genome encodes a single functional GAPDH gene.
 ...
PMID:Isolation and complete sequence of a functional human glyceraldehyde-3-phosphate dehydrogenase gene. 317 May 85

The regulation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene expression was studied during the onset of obesity in the genetically obese (fa/fa) rat by determination of GAPDH activity and hybridizable mRNA amounts in adipose tissue and liver from suckling and weanling rats. GADPH activity remained low throughout the suckling period, and a burst of activity occurred after weaning in both lean and obese pups. As early as 7 days of age, adipose tissue from pre-obese rats displayed a significant increase in enzyme activity, whereas no difference could be detected in the liver. In both suckling (16 days of age) and weanling (30 days of age) obese rats a proportionate increase in GAPDH activity and mRNA amounts was observed in adipose tissue, but not in liver. It is concluded that the obese genotype influences GAPDH gene expression at a pretranslational level and in a tissue-specific manner. This phenomenon could partly contribute to the hyperactive fat accretion in the obese rat, since glycolysis is the major metabolic pathway for lipogenic substrates in adipose tissue.
 ...
PMID:Adipose-tissue-specific increase in glyceraldehyde-3-phosphate dehydrogenase activity and mRNA amounts in suckling pre-obese Zucker rats. Effect of weaning. 317 70

To identify and characterize genes, the products of which play a role in pancreatic adenocarcinoma, we constructed a complementary DNA (cDNA) library using mRNA from the pancreatic adenocarcinoma cell line HPAF, grown as a nude mouse tumor. Through differential screening, we identified a cDNA clone, pII5B, that is homologous to an mRNA expressed at significantly higher levels in HPAF cells than in normal human pancreas. The pII5B cDNA was homologous to the 3'-untranslated region of glyceraldehyde-3-phosphate dehydrogenase (GAPDH, EC 1.2.1.12)mRNA. Partial sequencing of several HPAF tumor GAPDH cDNA clones revealed no significant differences from previously published GAPDH cDNA sequences. Increased levels of GAPDH mRNA, relative to actin mRNA levels, were found in six pancreatic adenocarcinoma cell lines and two nude mouse tumors, when compared to normal pancreas. Enolase and glucose transporter mRNA levels were also increased in HPAF cells and nude mouse tumor, suggesting a general increase in expression of genes associated with glycolysis in pancreatic adenocarcinoma. Levels of GAPDH protein were elevated in nude mouse tumors and fresh human pancreatic adenocarcinomas compared to normal pancreas. High GAPDH levels may be characteristic of human adenocarcinomas, since colon adenocarcinomas also exhibited high levels of GAPDH compared to normal colon.
 ...
PMID:Increased glyceraldehyde-3-phosphate dehydrogenase gene expression in human pancreatic adenocarcinoma. 318 54


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>