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:1.2.1.13 (glyceraldehyde-3-phosphate dehydrogenase)
6,511 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carbon-13 and deuterium isotope effects have been measured on the reaction catalyzed by rabbit muscle glyceraldehyde-3-phosphate dehydrogenase in an effort to locate the rate-limiting steps. With D-glyceraldehyde 3-phosphate as substrate, hydride transfer is a major, but not the only, slow step prior to release of the first product, and the intrinsic primary deuterium and 13C isotope effects on this step are 5-5.5 and 1.034-1.040, and the sum of the commitments to catalysis is approximately 3. The 13C isotope effects on thiohemiacetal formation and thioester phosphorolysis are 1.005 or less. The intrinsic alpha-secondary deuterium isotope effect at C-4 of the nicotinamide ring of NAD is approximately 1.4; this large normal value (the equilibrium isotope effect is 0.89) shows tight coupling of hydrogen motions in the transition state accompanied by tunneling. With D-glyceraldehyde as substrate, the isotope effects are similar, but the sum of commitments is approximately 1.5, so that hydride transfer is more, but still not solely, rate limiting for this slow substrate. The observed 13C and deuterium equilibrium isotope effects on the overall reaction from the hydrated aldehyde are 0.995 and 1.145, while the 13C equilibrium isotope effect for conversion of a thiohemiacetal to a thioester is 0.994, and that for conversion of a thioester to an acyl phosphate is 0.997. Somewhat uncertain values for the 13C equilibrium isotope effects on aldehyde dehydration and formation of a thiohemiacetal are 1.003 and 1.004.
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PMID:Carbon-13 and deuterium isotope effects on the reaction catalyzed by glyceraldehyde-3-phosphate dehydrogenase. 188 44

Modification of a single arginine residue per subunit of rabbit muscle tetrameric D-glyceraldehyde-3-phosphate dehydrogenase by 2,3-butanedione converts the enzyme into the form which retains 5-7% of the original activity and manifests cooperative properties that are absent in the native enzyme. It exhibits half-of-the-sites reactivity towards the natural substrate D-glyceraldehyde-3-phosphate. Titration of the modified enzyme with DTNB reveals only two instantaneously reacting SH groups, the total amount of SH groups approaching nine per tetramer. In the presence of 8 M urea, an additional seven SH groups become accessible to DTNB. This suggests that the arginine modification imposes some conformational constraints which affect the microenvironment of the active site cysteine residues in two subunits of the tetramer. The changes do not influence the interaction between the essential cysteine residue and NAD+ which is responsible for the change transfer complex formation, since the molar extinction coefficient of the apoenzyme-NAD+ complex, epsilon 360, was not altered upon the arginine modification. The native and close to four in the case of the native enzyme and about three with the modified one. The apparent pK values of Cys-149 within the functioning active centers of the tetramer were determined from the pH profiles of the inactivation rates in presence of iodoacetamide. The apparent pKa of the essential thiols was found to change upon enzyme modification from 9.44 to 10.07 in the apoenzyme and from 9.17 to 9.36 in the holoenzyme. The apparent pKa of the arginine residue determined from the pH dependence of the inactivation rate was equal to 9.0 and did not change upon apo-holo enzyme transition.
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PMID:Rabbit muscle tetrameric D-glyceraldehyde-3-phosphate dehydrogenase is locked in the asymmetric state by chemical modification of a single arginine per subunit. 193 68

Trypanosoma brucei contains two isoenzymes for glyceraldehyde-3-phosphate dehydrogenase: one enzyme resides in a microbody-like organelle, the glycosome; the other is found in the cytosol. Previously we have reported the characterization of the gene for the glycosomal enzyme [Michels, P. A. M., Poliszczak, A., Osinga, K. A., Misset, O., Van Beeumen, J., Wierenga, R. K., Borst, P. & Opperdoes, F. R. (1986) EMBO J. 5, 1049-1056]. Here we describe the cloning and analysis of the gene that codes for the cytosolic isoenzyme. The gene encodes a polypeptide of 330 amino acids, with a calculated molecular mass of 35440 Da. The two isoenzymes are only 55% identical. The cytosolic glyceraldehyde-3-phosphate dehydrogenase differs from the glycosomal enzyme in the following respects: (a) its subunit molecular mass is 3.4 kDa smaller due to the absence of insertions and a small C-terminal extension which are unique to the glycosomal protein; (b) the cytosolic enzyme has a lower pI (7.9, as compared to 9.3 for the glycosomal isoenzyme), which is due to a reduction in the excess of positively charged amino acids (the calculated net charges of the polypeptides are +2 and +11, respectively). We have compared the amino acid sequences of the two T. brucei glyceraldehyde-3-phosphate dehydrogenases, with 24 available sequences of the corresponding enzyme of other organisms from various phylogenetic groups. On the basis of this comparison an evolutionary tree was constructed. This analysis strongly supports the theory that T. brucei diverged early in evolution from the main eukaryotic branch of the phylogenetic tree. Further, two separate branches for the lineages leading to Trypanosoma are inferred from the amino acid sequences, suggesting that the genes for the two glyceraldehyde-3-phosphate dehydrogenases of the trypanosome are distantly related and must have been acquired independently by the trypanosomal ancestor. The branching determined with the glycosomal enzyme precedes that found with the cytosolic enzyme. The available data do not allow us to decide which of the two genes originally belonged to the trypanosome lineage and which entered the cell later by horizontal gene transfer.
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PMID:The cytosolic and glycosomal isoenzymes of glyceraldehyde-3-phosphate dehydrogenase in Trypanosoma brucei have a distant evolutionary relationship. 204 Mar 3

The inhibitory effects of vanadium(V) were determined on the oxidation of glycerol 3-phosphate (G3P) catalyzed by glycerol-3-phosphate dehydrogenase (G3PDH), an enzyme with a thiol group in the active site. G3PDH from rabbit muscle was inhibited by vanadate, and the active inhibiting species were found to be the vanadate dimer and/or tetramer. The dimer was a sufficiently weak inhibitor at pH 7.4 with respect to G3P; the tetramer could account for all the observed inhibition. The tetramer was a competitive inhibitor with respect to G3P with a Ki of 0.12 mM. Both the dimer and tetramer were noncompetitive inhibitors at pH 7.4 with respect to NAD with Ki's of 0.36 mM and 0.67 mM. G3PDH inhibited by vanadate was reactivated when EDTA complexed the vanadate. The reactivation occurred even after extended periods of incubation of G3PDH and vanadate, suggesting that the inhibition is reversible despite the thiol group in the active site. Analogous reactivation is also observed with glyceraldehyde-3-phosphate dehydrogenase (Gly3PDH). Gly3PDH is an enzyme that previously had been reported to undergo redox chemistry with vanadate. The work described in this paper suggests vanadate will not necessarily undergo redox chemistry with enzymes containing thiol groups exposed on the surface of the protein.
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PMID:Nonreductive interaction of vanadate with an enzyme containing a thiol group in the active site: glycerol-3-phosphate dehydrogenase. 206 57

The combination of binding and kinetic approaches is suggested to study (i) the mechanism of substrate-modulated dynamic enzyme associations; (ii) the specificity of enzyme interactions. The effect of complex formation between aldolase and glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12) on aldolase catalysis was investigated under pseudo-first-order conditions. No change in kcat but a significant increase in KM of fructose 1,6-bisphosphate for aldolase was found when both enzymes were obtained from muscle. In contrast, kcat rather than KM changed if dehydrogenase was isolated from yeast. Next, the conversion of fructose 1-phosphate was not affected by interactions between enzyme couples isolated from muscle. The influence of fructose phosphates on the enzyme-complex formation was studied by means of covalently attached fluorescent probe. We found that the interaction ws not perturbed by the presence of fructose 1-phosphate; however, fructose 1,6-bisphosphate altered the dissociation constant of the enzyme complex. A molecular model for fructose 1,6-bisphosphate-modulated enzyme interaction has been evaluated which suggests that high levels of fructose bisphosphate would drive the formation of the 'channelling' complex between aldolase and glyceraldehyde-3-phosphate dehydrogenase.
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PMID:Cooperative effect of fructose bisphosphate and glyceraldehyde-3-phosphate dehydrogenase on aldolase action. 210 14

Partition equilibrium experiments have been used to characterize the interactions of erythrocyte ghosts with four glycolytic enzymes, namely aldolase, glyceraldehyde-3-phosphate dehydrogenase, phosphofructokinase and lactate dehydrogenase, in 5 mM sodium phosphate buffer (pH 7.4). For each of these tetrameric enzymes a single intrinsic association constant sufficed to describe its interaction with erythrocyte matrix sites, the membrane capacity for the first three enzymes coinciding with the band 3 protein content. For lactate dehydrogenase the erythrocyte membrane capacity was twice as great. The membrane interactions of aldolase and glyceraldehyde-3-phosphate dehydrogenase were mutually inhibitory, as were those involving either of these enzymes and lactate dehydrogenase. Although the binding of phosphofructokinase to erythrocyte membranes was inhibited by aldolase, there was a transient concentration range of aldolase for which its interaction with matrix sites was enhanced by the presence of phosphofructokinase. In the presence of a moderate concentration of bovine serum albumin (15 mg/ml) the binding of aldolase to erythrocyte ghosts was enhanced in accordance with the prediction of thermodynamic nonideality based on excluded volume. At higher concentrations of albumin, however, the measured association constant decreased due to very weak binding of the space-filling protein to either the enzyme or the erythrocyte membrane. The implications of these findings are discussed in relation to the likely subcellular distribution of glycolytic enzymes in the red blood cell.
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PMID:Interactions of glycolytic enzymes with erythrocyte membranes. 214 Feb 76

Two independent cis-acting insulin response elements (IREs) in the gene encoding glyceraldehyde-3-phosphate dehydrogenase [D-glyceraldehyde-3-phosphate: NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12], designated IRE-A and IRE-B, are sufficient to direct insulin-inducible gene expression. Using the electrophoretic mobility shift assay, a 4-fold increase in the amount of IRE-A DNA bound to nuclear proteins was detected when extracts isolated from insulin-stimulated differentiated 3T3-L1 cells or from the liver of rats refed a high-carbohydrate/low-fat diet after a 72-hr fast were compared to control nuclear extracts. The points of contact between protein and IRE-A DNA may represent a sequence recognized by at least one class of insulin-sensitive transcription factor(s).
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PMID:An insulin response element in the glyceraldehyde-3-phosphate dehydrogenase gene binds a nuclear protein induced by insulin in cultured cells and by nutritional manipulations in vivo. 216 73

The glyceraldehyde-3-phosphate dehydrogenase from the hyperthermophilic archaebacterium Pyrococcus woesei (optimal growth temperature, 100 to 103 degrees C) was purified to homogeneity. This enzyme was strictly phosphate dependent, utilized either NAD+ or NADP+, and was insensitive to pentalenolactone like the enzyme from the methanogenic archaebacterium Methanothermus fervidus. The enzyme exhibited a considerable thermostability, with a 44-min half-life at 100 degrees C. The amino acid sequence of the glyceraldehyde-3-phosphate dehydrogenase from P. woesei was deduced from the nucleotide sequence of the coding gene. Compared with the enzyme homologs from mesophilic archaebacteria (Methanobacterium bryantii, Methanobacterium formicicum) and an extremely thermophilic archaebacterium (Methanothermus fervidus), the primary structure of the P. woesei enzyme exhibited a strikingly high proportion of aromatic amino acid residues and a low proportion of sulfur-containing residues. The coding gene of P. woesei was expressed at a high level in Escherichia coli, thus providing an ideal basis for detailed structural and functional studies of that enzyme.
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PMID:Glyceraldehyde-3-phosphate dehydrogenase from the hyperthermophilic archaebacterium Pyrococcus woesei: characterization of the enzyme, cloning and sequencing of the gene, and expression in Escherichia coli. 216 75

Male Wistar rats were given a single i.v. injection of lead nitrate (10 mumol/100 g body wt) and were killed with matched controls 24, 48, 72 h and 20 days after the treatment. Changes of liver carbohydrate metabolism were studied histochemically testing the following parameters: glycogen content, activities of glycogen synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6PASE), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In addition, gammaglutamyltransferase (GGT) activity was demonstrated. Between 24 and 48 h after lead nitrate injection there was a nearly complete loss of liver glycogen. Seventy-two hours later the polysaccharide reappeared in single hepatocytes and after 20 days the livers of the lead-treated animals not only had replenished their glycogen stores but contained even more glycogen than the matched controls. SYN and PHO activities were diminished from 24 to 72 h, but returned to control values after 20 days. G6PASE and GGT remained elevated up to 72 h before dropping to normal at 20 days after treatment. The pentose phosphate pathway enzymes G6PDH and 6PGDH showed the most remarkable changes in livers treated with lead nitrate. G6PDH was already elevated at 24 h, but only in Kupffer cells. At 48 and 72 h, when hepatocytes exhibited a highly increased mitotic rate, the levels of G6PDH, 6PGDH and GAPDH were elevated. After 20 days dehydrogenase activities were comparable to those of controls. The results of this study suggest that a single dose of lead nitrate not only stimulates proliferation of hepatocytes but also induces considerable changes in rat liver carbohydrate metabolism, especially between 24 and 72 h after administration. During that period glycogen metabolism undergoes a strong reduction, whereas gluconeogenesis and particularly the pentose phosphate pathway respond with a remarkable increase. This metabolic profile is most likely associated with lead biotransformation as well as with liver cell proliferation. It corresponds only partially to that found in preneoplastic and neoplastic liver lesions observed in chemical carcinogenesis, and is reversible, in contrast to the persistent alterations associated with neoplastic transformation.
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PMID:Effect of lead nitrate on liver carbohydrate enzymes and glycogen content in the rat. 217 37

We assessed our speculation that 2-cyclohexen-1-one (CHX) impairs glucose-induced insulin secretion through inactivation of glucokinase. Treatment of pancreatic islets with CHX at concentrations (0-5 mM) that caused a dose-dependent inactivation of glucokinase activity similarly inhibited glucose-induced insulin secretion. Another glucose-phosphorylating enzyme (hexokinase) in pancreatic islets was little affected by CHX. CHX-induced inactivation of glucokinase was blocked by the presence of its substrates (glucose and mannose) and an inhibitor (N-acetylglucosamine), all of which also protected against the inhibitory effect of the drug on glucose-induced insulin secretion. CHX also impaired insulin secretion induced by D-glyceraldehyde and dimethyl succinate, which are believed to stimulate the release of the hormone by being directly oxidized by glyceraldehyde-3-phosphate dehydrogenase, by entering the midstream of the glycolytic pathway as glyceraldehyde 3-phosphate, or by entering the tricarboxylic acid cycle in mitochondria after intracellular hydrolysis. The inhibitory effect of CHX on glucose-induced insulin secretion, however, was far more marked than that on insulin secretion evoked by D-glyceraldehyde and dimethyl succinate at any CHX concentrations used. Our study revealed that the inhibitory action of CHX on glucose-induced insulin secretion is exerted mainly, but not solely, through inactivation of glucokinase. This conclusion supports the view that glucokinase is a key enzyme in the recognition of glucose as an insulin secretagogue in pancreatic islets.
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PMID:Participation of glucokinase inactivation in inhibition of glucose-induced insulin secretion by 2-cyclohexen-1-one. 221 70


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