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)

Ten years ago, the term "oxidative stress" (sigma -O2) was created to define oxidative damage inflicted to the organism. This definition brings together processes involving reactive oxygen species production and action such as free radical production during univalent reduction of oxygen within mitochondria, activation of NADPH-dependent oxidase system on the membrane surface of neutrophils, flavoprotein-catalyzed redox cycling of xenobiotics and exposure to chemical and physical agents in the environment. Since the discovery of the nitric oxide biosynthetic pathway, the deleterious effects of uncontrolled nitric oxide generation are generally classified as oxidative stress. Indeed, products of the reaction of NO and superoxide lead to oxidants such as peroxinitrite, nitrogen dioxide and hydroxyl radical, which are involved in mechanisms of cell-mediated immune reactions and defence of the intracellular environment against microbiol invasion. However NO can also regulate many biological reactions and signal transduction pathways that lead to a variety of physiological responses such as blood pressure, neurotransmission, platelet aggregation, endothelin generation or smooth muscle cell proliferation. Then the uncontrolled NO production can lead to a variety of physiological and pathophysiological responses similar to a Nitric Oxide Stress: activation of guanylate cyclase and production of cGMP: overstimulation of the inducible L-arginine to L-citrulline and NO pathway by bactericidal endotoxins and cytokines has been shown to promote undesired increases in vasodilatation, which may account for hypotension in septic shock and cytokine therapy. stimulation of auto-ADP-ribosylation and modification of SH-groups of glyceraldehyde-3-phosphate dehydrogenase in a cGMP-independent mechanism: by this way, NO in excess can strongly inhibits this important glycolytic enzyme and reduce the cellular energy production. inhibition of ribonucleotide reductase: extensive inhibition of this key enzyme in DNA synthesis in the presence of large amounts of NO could lead to important antiproliferative effects; inhibition of cytochrome P450-dependent metabolism: in Kupffer cells and hepatocytes, LPS-induced overproduction of NO has been shown to inhibit cytochrome P450-dependent metabolism and to mediate the suppression of hepatic metabolism. Moreover, NO synthetized in the peripheral nervous system is known to mediate nonadrenergic noncholinergic (NANC) neurotransmission. Overstimulation of NO synthases might therefore contribute to pathophysiological states such as: gastrointestinal motility, reflux oesophagitis, asthma, adult respiratory distress syndrome (ARDS) and chronic pulmonary artery hypertension. To these NO-mediated biological functions, one could add the biological effects of NO-derivatives such as N-nitrosocompounds, which act as carcinogenic agents, or C-nitrosocompound which were recently used as "zinc-ejecting" agents to inhibit HIV-1 infectivity of human T-lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Does nitric oxide stress exist?]. 852 Oct 87

Spinach chloroplast NAD(P)-glyceraldehyde-3-phosphate dehydrogenase (NAD(P)-GAPDH; EC, 1.2.1.13) was purified as the 600-kDa oligomer of low specific activity. Incubation of the enzyme with either a reductant or a 1,3-bisphosphoglycerate (1,3bisPGA) generating system, but most effectively with both, resulted in an increase of the apparent NADPH-dependent activity. Only the 1,3bisPGA treatment caused dissociation and yielded the 150-kDa heterotetramer (A2B2). The higher activity of the tetramer is largely due to a decreased KM value for the substrate 1,3bisPGA. Reductive treatment alone does not dissociate the enzyme. Reduction was equally effective with glutathione as with dithiothreitol or with reduced thioredoxin f. The concentration of 1,3bisPGA required to obtain 50% activity (K alpha) was 19.5 +/- 4.1 microM for the untreated enzyme and 2.0 +/- 1.4 microM for the thiol-pretreated enzyme. Thus, in vitro 1,3bisPGA, alone or--at much lower concentrations--together with a reductant can activate (and dissociate) NAD(P)-GAPDH. The enzyme exhibits similar K alpha values in its reduced and its oxidized form for ATP (1-2 mM), NADP (50-200 microM), and NADPH (0.3-0.5 mM) as positive effectors, but these effectors do not lead to any activation when present together with 0.14 mM NAD. Only 1,3bisPGA retained its characteristic effect in the presence of NAD. The dissociated enzyme reaggregates upon removal of the positive effectors. From these results it is concluded (i) that the role of the reduction of the NAD(P)-GAPDH in vivo is to increase its sensitivity toward the activator 1,3bisPGA and (ii) that the actual activation (and aggregation) state of the enzyme in chloroplasts in the light is regulated by the concentration of 1,3bisPGA as activator in the stroma and its actual activity by the availability of 1,3bisPGA as substrate.
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PMID:Reductive modification and nonreductive activation of purified spinach chloroplast NADP-dependent glyceraldehyde-3-phosphate dehydrogenase. 855 10

NADP-dependent glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been purified to electrophoretic homogeneity from Synechococcus PCC 7942 cells. The native enzyme had a molecular mass of 160 kDa and consisted of four subunits with a molecular mass of 41 kDa. The activity was 6-fold higher with NADPH than with NADH; the apparent Km values for NADPH and NADH were 62 +/- 4.5 and 420 +/- 10.5 microM respectively. The gene encoding NADP-dependent GAPDH was cloned from the chromosomal DNA of Synechococcus 7942. A 1140 bp open reading frame, encoding an enzyme of 380 amino acid residues (approx.molecular mass of 41.3 kDa) was observed. The deduced amino acid sequence of the gene had a greater sequence similarity to the NADP-dependent and chloroplastic form than to the NAD-dependent and cytosolic form. The Synechococcus 7942 enzyme lacked one of the cysteines involved in the light-dependent regulation of the chloroplast enzymes of higher plants. The recombinant enzyme expressed in Escherichia coli as well as the native enzyme purified from Synechococcus 7942 cells were resistant to 1 mM H2O2.
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PMID:Enzymic and molecular characterization of NADP-dependent glyceraldehyde-3-phosphate dehydrogenase from Synechococcus PCC 7942: resistance of the enzyme to hydrogen peroxide. 868 18

The objective of this study was to determine whether the concentration of pyridine nucleotides in muscle and liver tissue of quail affected the heat stability of aldolase and selected enzymes involved in the oxidation-reduction of these cofactors. The thermal stability of malic enzyme, glyceraldehyde-3-phosphate dehydrogenase, lactic dehydrogenase, and aldolase in liver, and in pectoral muscle of quail was studied at incubation temperatures ranging from 27 to 60 degrees C. The concentrations of liver NAD, NADP, NADPH and the thermal inactivation of liver malic enzyme, glyceraldehyde-3-phosphate dehydrogenase, lactic dehydrogenase, and aldolase were not affected by niacin deficiency. In contrast, pectoral muscle glyceraldehyde-3-phosphate dehydrogenase in the niacin deficient quail compared to that of the controls had a markedly reduced thermal stability. This was associated with a corresponding decrease in the concentration of NAD and possibly NADPH. However, lactic dehydrogenase and aldolase activities were not affected. A similar pattern of heat inactivation was obtained when dialysed muscle and liver extracts were spiked with NAD or NADP. In these studies, NAD(P) protected muscle glyceraldehyde-3-phosphate dehydrogenase against heat inactivation to a much greater degree than that obtained with the other enzymes from muscle or liver tissue. These results suggest a causative relationship between the thermal stability of glyceraldehyde-3-phosphate dehydrogenase and coenzyme status in pectoral muscle tissue. This effect of niacin deficiency on the thermal stability of enzymes appears to be quite selective and specific.
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PMID:Effect of niacin deficiency on the thermal stability of NAD- and NADP-dependent dehydrogenases in liver and pectoral muscle of Japanese quail. 893 Jan 42

CP12 is a small nuclear encoded chloroplast protein of higher plants, which was recently shown to interact with NAD(P)H-glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1. 13), one of the key enzymes of the reductive pentosephosphate cycle (Calvin cycle). Screening of a pea cDNA library in the yeast two-hybrid system for proteins that interact with CP12, led to the identification of a second member of the Calvin cycle, phosphoribulokinase (PRK; EC 2.7.1.19), as a further specific binding partner for CP12. The exchange of cysteines for serines in CP12 demonstrate that interaction with PRK occurs at the N-terminal peptide loop of CP12. Size exclusion chromatography and immunoprecipitation assays reveal the existence of a stable 600-kDa PRK/CP12/GAPDH complex in the stroma of higher plant chloroplasts. Its stoichiometry is proposed to be of two N-terminally dimerized CP12 molecules, each carrying one PRK dimer on its N terminus and one A2B2 complex of GAPDH subunits on the C-terminal peptide loop. Incubation of the complex with NADP or NADPH, in contrast to NAD or NADH, causes its dissociation. Assays with the stromal 600-kDa fractions in the presence of the four different nicotinamide-adenine dinucleotides indicate that PRK activity depends on complex dissociation and might be further regulated by the accessible ratio of NADP/NADPH. From these results, we conclude that light regulation of the Calvin cycle in higher plants is not only via reductive activation of different proteins by the well-established ferredoxin/thioredoxin system, but in addition, by reversible dissociation of the PRK/CP12/GAPDH complex, mediated by NADP(H).
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PMID:CP12 provides a new mode of light regulation of Calvin cycle activity in higher plants. 929 36

A cDNA fragment coding for the pea (Pisum sativum L.) chloroplastic glyceraldehyde-3-P dehydrogenase (EC 1.2.1.13) B-subunit and a truncated form corresponding in length to the A-subunit have been cloned into an expression vector, expressed in the absence of the A-subunit in a gap- Escherichia coli strain, purified, and studied. Like the isolated enzyme from higher plant chloroplasts, the recombinant enzymes have dual specificity for NADPH and NADH. The recombinant glyceraldehyde-3-P dehydrogenases have the same optimal pH as the enzyme isolated from pea chloroplasts. Like the native chloroplast enzyme, the recombinant B-subunit has a marked tendency to form large aggregates, whereas the truncated B-subunit exists as the tetramer. The recombinant B-subunit glyceraldehyde 3-P dehydrogenase is more sensitive to dithiothreitol than its truncated form. It seems likely that a different pair of cysteines is responsible for the redox sensitivity of the activity of the enzyme composed of B-subunits than the cysteine residues implicated in the modulation of the activity of the enzyme composed of A-subunits by previous work in this laboratory.
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PMID:Expression and characterization of pea chloroplastic glyceraldehyde-3-phosphate dehydrogenase composed of only the B-subunit. 939 Apr 45

The non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase catalyses the irreversible reaction of glyceraldehyde-3-phosphate to 3-phosphoglycerate by the reduction of NADP to NADPH. This is in contrast to the extensively analysed phosphorylating glyceraldehyde-3-phosphate dehydrogenases which catalyse the reversible reaction of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate. Sequence analysis revealed that the non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase is not related to the phosphorylating glyceraldehyde-3-phosphate dehydrogenases but a member of the aldehyde dehydrogenase superfamily. The aldehyde dehydrogenases are of ancient origin and they have already existed in the progenote as indicated by phylogenetic analysis. Thus the non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase can be found in all three domains, archaea, bacteria and eukarya. The catalytic mechanism of the non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase and the other aldehyde dehydrogenases resembles a thioester mechanism involving the universally conserved cysteine 298 (pea GAPN). The cofactor of the aldehyde dehydrogenases is bound in a new mode to a structure described as beta-alpha,beta-fold.
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PMID:The non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase: biochemistry, structure, occurrence and evolution. 946 40

Growth of Corynebacterium glutamicum on fructose was significantly less than that obtained on glucose, despite similar rates of substrate uptake. This was in part due to the production of overflow metabolites (dihydroxyacetone and lactate) but also to the increased production of CO2 during growth on fructose. These differences in carbon-metabolite accumulation are indicative of a different pattern of carbon-flux distribution through the central metabolic pathways. Growth on glucose has been previously shown to involve a high flux (> 50% of total glucose consumption) via the pentose pathway to generate anabolic reducing equivalents. NMR analysis of carbon-isotope distribution patterns of the glutamate pool after growth on 1-13C- or 6-13C-enriched fructose indicates that the contribution of the pentose pathway is significantly diminished during exponential growth on fructose with glycolysis being the predominant pathway (80% of total fructose consumption). The increased flux through glycolysis during growth on fructose is associated with an increased NADH/NAD+ ratio susceptible to inhibit both glyceraldehyde-3-phosphate dehydrogenase and pyruvate dehydrogenase, and provoking the overflow of metabolites derived from the substrates of these two enzymes. The biomass yield observed experimentally is higher than can be estimated from the apparent quantity of NADPH associated with the pentose pathway and the flux through isocitrate dehydrogenase, suggesting an additional reaction yielding NADPH. This may involve a modified tricarboxylic acid cycle involving malic enzyme, expressed to significantly higher levels during growth on fructose than on glucose, and a pyruvate carboxylating anaplerotic enzyme.
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PMID:Carbon-flux distribution in the central metabolic pathways of Corynebacterium glutamicum during growth on fructose. 965

For higher plant chloroplasts, two key enzymes of the Calvin cycle, phosphoribulokinase (EC 2.7.1.19) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH, EC 1.2.1.13), have recently been shown to be oligomerized onto the nonenzymatic peptide CP12. Enzymatic activity depends on complex dissociation, mediated by NADPH. The discovery of genes for CP12 in mosses, green algae, and cyanobacteria, together with the analysis of equivalent multiprotein complexes of Chlamydomonas and Synechocystis suggests that light regulation of Calvin cycle activity via NADPH-mediated reversible phosphoribulokinase/CP12/GAPDH complex dissociation is conserved in all photosynthetic organisms, prokaryotes and eukaryotes. In vitro complex reconstitution assays with heterologously expressed Synechocystis wild-type and mutagenized CP12 demonstrate a conserved subunit composition, stoichiometry, and topology in this complex. Further finding of genes, coding for chimeric proteins, carrying CP12 or parts of it as genetic fusions, indicates that evolution has used the peptide loops of CP12 as universal modules to keep various enzymatic activities under the control of NADP(H). These fusion events occurred at least twice in evolution. First was the fusion of the duplicated genes for CP12 and the ORF4 protein of Anabaena variabilis to the chimeric gene for the heterocyst-specific expressed ORF3 protein, most probably involved in N2 fixation. A second gene fusion, which led to the higher plant chloroplast-specific GAPDH subunit, GAPB, has taken place during the transition from water- to land plants.
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PMID:Evolutionary conserved light regulation of Calvin cycle activity by NADPH-mediated reversible phosphoribulokinase/CP12/ glyceraldehyde-3-phosphate dehydrogenase complex dissociation. 968 44

The effects of niacin deficiency on the levels of soluble proteins and enzyme activities of Japanese quail have been investigated. SDS-polyacrylamide gel electrophoresis revealed that in the pectoral muscle the soluble proteins with molecular masses corresponding to 181, 128, 93, 76, 72, 62, 56, 43, 41, 28 and 20 kDa were present in lower amounts but those of 60, 50 and 37 kDa were present in higher amounts. In the heart the soluble proteins with a molecular mass of 181 kDa were present in lower amounts and in the brain those of 43 kDa were present in lower amounts but those of 221 kDa were present in higher amounts. In the intestine the soluble proteins with molecular masses corresponding to 181, 102, 83, 74, 72, 44 and 40 kDa were present in lower amounts but those of 41 kDa and 18 kDa were present in higher amounts. There was a marked reduction in the level of NAD and NADPH in the pectoral muscle of niacin deficient quail but not in other tissues. The specific activity of glyceraldehyde-3-phosphate dehydrogenase decreased markedly both in the liver and pectoral muscle of niacin deficient quail whereas that of 6-phosphogluconate dehydrogenase and malic enzyme decreased markedly in the liver or pectoral muscle, respectively. In contrast, the specific activity of acetylcholinesterase and carboxypeptidase increased markedly in the liver or the pectoral muscle, respectively. The results suggest that a severe niacin deficiency exerted specific effects on levels of some soluble proteins particularly in the pectoral muscle and intestine and on activities of certain enzymes in the liver and the pectoral muscle.
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PMID:Effects of niacin deficiency on the levels of soluble proteins and enzyme activities in various tissues of Japanese quail. 974 85


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