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)

We investigated the role of oxygen free radicals in the modulation of glyceraldehyde-3-phosphate dehydrogenase binding to the erythrocyte membrane. Previous studies have demonstrated that in vitro tyrosine phosphorylation of Band 3 prevents the binding of various glycolytic enzymes to its cytoplasmic domain. Since these enzymes are inhibited in their bound state, the functional consequence of Band 3 tyrosine phosphorylation in red blood cells should be to increase glycolysis. To generate free radicals, we used an azo-compound, the hydrophilic 2,2'-azobis(2-amidinopropane) hydrochloride, which, at 37 degrees C and in the presence of oxygen, decomposes and produces peroxyl radicals at a constant rate. The reaction of peroxyl radicals with intact red cells induced a time-dependent loss of the membrane-bound glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase, associated with a concomitant decrease in enzyme activity. At the same time, Band 3 was phosphorylated in tyrosine. These results were completely reversible in plasma after removal of the oxidative stress. The peroxyl radicals also enhanced the production of lactate in intact cells. Our data reveal a powerful mechanism of erythrocyte metabolic regulation that can boost or reduce energy production in times of special need such as during a free radical attack.
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PMID:Free radicals induce reversible membrane-cytoplasm translocation of glyceraldehyde-3-phosphate dehydrogenase in human erythrocytes. 754 96

Genes for glycolytic and Calvin-cycle glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of higher eukaryotes derive from ancient gene duplications which occurred in eubacterial genomes; both were transferred to the nucleus during the course of endosymbiosis. We have cloned cDNAs encoding chloroplast and cytosolic GAPDH from the early-branching photosynthetic protist Euglena gracilis and have determined the structure of its nuclear gene for cytosolic GAPDH. The gene contains four introns which possess unusual secondary structures, do not obey the GT-AG rule, and are flanked by 2- to 3-bp direct repeats. A gene phylogeny for these sequences in the context of eubacterial homologues indicates that euglenozoa, like higher eukaryotes, have obtained their GAPDH genes from eubacteria via endosymbiotic (organelle-to-nucleus) gene transfer. The data further suggest that the early-branching protists Giardia lamblia and Entamoeba histolytica--which lack mitochondria--and portions of the trypanosome lineage have acquired GAPDH genes from eubacterial donors which did not ultimately give rise to contemporary membrane-bound organelles. Evidence that "cryptic" (possibly ephemeral) endosymbioses during evolution may have entailed successful gene transfer is preserved in protist nuclear gene sequences.
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PMID:A nuclear gene of eubacterial origin in Euglena gracilis reflects cryptic endosymbioses during protist evolution. 756 85

As demonstrated previously, liver acini draining the blood from intraportally transplanted pancreatic islets in streptozotocin-diabetic rats are altered in various respects. The hepatocytes in these acini store glycogen and/or fat, and they show an increase in proliferation as well as in apoptotic activity. Thus, they are phenotypically similar to carcinogen-induced preneoplastic liver foci (glycogen-storing foci and sometimes also mixed cell foci). By means of catalytic enzyme histochemistry or immunohistochemistry, we investigated the activity of key enzymes of alternative pathways of carbohydrate metabolism and some additional marker enzymes (well known from studies on preneoplastic hepatic foci) in the altered liver acini surrounding the islet isografts. In addition, the expression of glucose transporter proteins 1 and 2 (GLUT-1 and GLUT-2) were investigated immunohistochemically. The activities of hexokinase, pyruvate kinase, glyceraldehyde-3-phosphate dehydrogenase, and glucose-6-phosphate dehydrogenase were increased, whereas the activities of glycogen phosphorylase, adenylate cyclase, glucose-6-phosphatase, and membrane-bound adenosine triphosphatase were decreased in the altered liver acini. The expression of GLUT-2 was also decreased. GLUT-1 and glutathione S-transferase placental form were not expressed, and the activities of glycogen synthase and gamma-glutamyl-transferase remained unchanged. All changes of the enzyme activities were in line with the well known effects of insulin and resembled alterations characteristic of preneoplastic liver foci observed in different models of hepatocarcinogenesis. It remains to be clarified in long-term experiments whether or not these foci represent preneoplastic lesions and may proceed to neoplasia.
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PMID:Altered liver acini induced in diabetic rats by portal vein islet isografts resemble preneoplastic hepatic foci in their enzymic pattern. 864 65

Interactions of NAD-dependent dehydrogenases (glyceraldehyde-3-phosphate dehydrogenase, GAPDH, and lactate dehydrogenase, LDH) with band 3 erythrocyte membrane protein and tubulin were characterized. At low ionic strength and un-saturating substrate concentrations, LDH tightly binds to tubulin and is thus inactivated. The Kd of the LDH-tubulin complex was calculated in inhibition and direct binding experiments (15.0 and 13.6 nM, respectively); the stoichiometry of the complex was 1.66 moles of tubulin dimer bound per mole of LDH tetramer. In the presence of 0.15 M NaCl, LDH does not bind to tubulin and tubulin-dependent inhibition of LDH activity is not detected. At low ionic strength, erythrocyte membranes affect both dehydrogenases similarly. GAPDH activity is completely inhibited by excess of erythrocyte membranes (or by excess of cytoplasmic fragment of band 3 protein). Under similar conditions, LDH activity was inhibited by 70% by erythrocyte membranes. In these experiments, 14.8.10(6) GAPDH tetramers or 25.6.10(6) LDH tetramers bound to one erythrocyte ghost (Kd is 0.13 and 0.6 microM, respectively). Increase in ionic strength (0.15 m NaCl) completely abolished the membrane-dependent inhibition of dehydrogenases; however, membranes still bound GAPDH and LDH. Under these conditions, the Kd for GAPDH was increased (up to 4.43 microM), whereas the number of membrane-bound enzyme molecules has not been significantly affected (0.75 nmoles of tetramer per 100 micrograms membrane protein). The Kd for LDH was not changed (0.76 microM), whereas the number of membrane-bound enzyme molecules was decreased (down to 0.48 nmoles of tetramer per 100 micrograms membrane protein). It is suggested that at low ionic strength, the "acidic tails" of band 3 protein and tubulin can interact with positively charged NAD-binding domains of both dehydrogenases thus inhibiting their activity. Increase in ionic strength reduces these interactions, decreasing the binding and inhibition of enzyme activities. At "physiological" ionic strength, catalytically active GAPDH and LDH can possibly bind to various sites of the erythrocyte membrane. This can be important in regulation of the transfer of the common cofactor (NAD/NADH) between their active sites.
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PMID:[Effect of erythrocyte membranes and tubulin on the activity of NAD-dependent dehydrogenases]. 896 25

The function of the membrane-bound ATPase in S. mutans is to regulate cytoplasmic pH values for the purpose of maintaining delta pH. Previous studies have shown that as part of its acid-adaptive ability, S. mutans is able to increase H(+)-ATPase levels in response to acidification. As part of the study of ATPase regulation in S. mutans, we have cloned the ATPase operon and determined its genetic organization. The structural genes from S. mutans were found to be in the order: c, a, b, delta, alpha, gamma, beta, and epsilon; where c and a were reversed from the more typical bacterial organization. The operon contained no I gene homologue but was preceded by a 239-bp intergenic space. Deduced aa sequences from open reading frames indicated that genes encoding homologues of glycogen phosphorylase and nonphosphorylating, NADP-dependent glyceraldehyde-3-phosphate dehydrogenase flank the H(+)-ATPase operon, 5' and 3' respectively. Sequence analysis indicated the presence of three inverted-repeat nt sequences in the glgP-uncE intergenic space. Primer extension analysis of mRNAs prepared from batch-grown or steady-state cultures demonstrated that the transcriptional start site did not change as a function of culture pH value. The data suggest that potential stem-and-loop structures in the promoter region of the operon do not function to alter the starting position of ATPase-specific mRNA transcription.
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PMID:Cloning and nucleotide sequence analysis of the Streptococcus mutans membrane-bound, proton-translocating ATPase operon. 899 91

Interaction of D-glyceraldehyde-3-phosphate dehydrogenase (GPDH) and lactate dehydrogenase with human erythrocyte membranes was studied. Under the conditions of low ionic strength, both enzymes bound to the membranes with similar affinities (kd = 1 microM). The binding was accompanied by complete inhibition of GPDH and by a 65-75% inhibition of lactate dehydrogenase (LDH). Increasing the ionic strength to physiologically meaningful values (0.15 M) completely abolished the inactivation of both dehydrogenases in the presence of erythrocyte membranes, but did not preclude their binding. These results suggest that different modes of enzyme-membrane interaction can be realized under the conditions of low and high ionic strength. They also indicate that GPDH and LDH are capable of functioning in a membrane-bound state.
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PMID:Interaction of NAD-dependent dehydrogenases with human erythrocyte membranes. Evidence that D-glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase are catalytically active in a membrane-bound state. 910 Mar 43

Further evidence is provided that the Calvin cycle enzymes ribose-5-phosphate isomerase (EC 5.3.1.6), ribulose-5-phosphate kinase (Ru-5-P-K, EC 2.7.1.19), ribulose-1,5-bisphosphate carboxylase (RuP2Case, EC 4.1.1.39), glyceraldehyde-3-phosphate dehydrogenase (GAPDH, EC 1.2.1.12), sedoheptulose-1,7-bisphosphatase (Sed-1,7-bPase, EC 3.1.3.37), and electron transport protein ferredoxin-NADP+ reductase (FNR, EC 1.18.1.1) are organized into stable CO2-fixing multienzyme complexes with a molecular mass of 900 kDa. Limited trypsinolysis combined with immunoblotting revealed that all of chloroplast stromal Ru-5-P-K and GAPDH is located in enzyme complexes. The Calvin cycle enzyme complexes remain intact indefinitely at lower ionic strength but dissociate into components at KCl concentrations >250 mM. Immunoelectron microscopy showed that Ru-5-P-K, GAPDH, Sed-1,7-bPase, and FNR are bound to stroma-faced thylakoid membranes in situ, whereas RuP2Case and RuP2Case activase are randomly distributed throughout chloroplasts. The results indicate that membrane-bound enzyme supercomplexes may play an important role in photosynthesis.
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PMID:Calvin cycle multienzyme complexes are bound to chloroplast thylakoid membranes of higher plants in situ. 1160 6

The ribosome-associated Trigger Factor (TF) cooperates with the DnaK system to assist the folding of newly synthesized polypeptides in Escherichia coli. TF unifies two functions in one to promote proper protein folding in vitro. First, as a chaperone it binds to unfolded protein substrates, thereby preventing aggregation and supporting productive folding. Second, TF catalyzes the cis/trans isomerization of peptidyl-prolyl bonds, which can be a rate-limiting step in protein folding. Here, we investigated whether the peptidyl-prolyl cis/trans isomerase (PPIase) function is essential for the folding activity of TF in vitro and in vivo by separating these two TF activities through site-directed mutagenesis of the PPIase catalytic center. Of the four different TF variants carrying point mutations in the PPIase domain, only the exchange of the conserved residue Phe-198 to Ala (TF F198A) abolished the PPIase activity of TF toward both a tetrapeptide and the model protein substrate RNase T1 in vitro. In contrast, all other activities of TF F198A tested were comparable with wild type TF. TF F198A retained a similar binding specificity toward membrane-bound peptides, assisted the refolding of denatured d-glyceraldehyde-3-phosphate dehydrogenase in vitro, and associated with nascent polypeptides in an in vitro transcription/translation system. Importantly, expression of the TF F198A encoding gene complemented the synthetic lethality of DeltatigDeltadnaK cells and prevented global protein misfolding at temperatures between 20 and 34 degrees C in these cells. We conclude that the PPIase activity is not required for the function of TF in folding of newly synthesized proteins.
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PMID:Trigger factor peptidyl-prolyl cis/trans isomerase activity is not essential for the folding of cytosolic proteins in Escherichia coli. 1472 69

Neurokinin-1 receptor (NK-1R), a high-affinity plasma membrane-bound receptor for neurokinin substance P, plays important roles in the onset of the pathophysiological responses. To test whether the transcript levels of gene encoding NK-1R in organs are affected by sidestream cigarette smoke (SSCS) exposure, the C57BL/6 mice were randomly assigned to five groups (six/group) in a study of the dose-effect relationship. The mice were exposed to 0 (filtered room air), 2, 4, 8 and 16 mg total particulate matter (TPM) of SSCS/exposure/day, respectively, for seven days through a nose-only exposure chamber (IN-TOX, Albuquerque, NM, USA). The levels of NK-1R mRNA in the lung, heart, liver, kidney and spleen tissues were detected by reverse transcription-polymerase chain reaction (RT-PCR) techniques and normalized against GAPDH expression. NK-1R mRNA in heart tissue showed SSCS-induced dose-dependent downregulation, with minimum expression at a dose of 8.0 mg TPM. Whereas, the levels of NK-1R mRNA in the liver were upregulated to 2.86 and 5.13-fold after exposure to 2.0 and 4.0 mg TPM of SSCS respectively, then returned to 4.19 and 3.93-fold at the exposure doses of 8.0 and 16.0 mg TPM, respectively, when compared to that of the control. In the kidney, SSCS exposure at a dose of 2.0 TPM, but not higher than that level, induced significant elevation of NK-1R mRNA expression. These findings suggest that there are the paracrine and/or autocrine signalling mechanisms through receptor-ligand interactions. No alteration of NK-1R gene expression was observed in the lungs and spleen tissues in this study. The tissue-specific patterns by which SSCS affect NK-1R gene expression in these organs may partially explain dissimilarity of NK-1R activation and the associated toxicity caused by environmental tobacco smoke.
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PMID:Tissue-specific patterns of neurokinin-1 receptor (NK-1R) gene expression in mice exposed to sidestream cigarette smoke. 1522 33

In the past few years, 8 additional members of the facilitative hexose transporter family have been identified, giving a total of 14 members of the SLC2A family of membrane-bound hexose transporters. To determine which of the new hexose transporters were expressed in muscle, mRNA concentrations of 11 glucose transporters (GLUTs) were quantified and compared. RNA from muscle from 10 normal volunteers was subjected to RT-PCR. Primers were designed that amplified 78- to 241-base fragments, and cDNA standards were cloned for GLUT1, GLUT2, GLUT3, GLUT4, GLUT5, GLUT6, GLUT8, GLUT9, GLUT10, GLUT11, GLUT12, and GAPDH. Seven of these eleven hexose transporters were detectable in normal human muscle. The rank order was GLUT4, GLUT5, GLUT12, GLUT8, GLUT11, GLUT3, and GLUT1, with corresponding concentrations of 404 +/- 49, 131 +/- 14, 33 +/- 4, 5.5 +/- 0.5, 4.1 +/- 0.4, 1.2 +/- .0.1, and 0.9 +/- 0.2 copies/ng RNA (means +/- SE), respectively, for the 10 subjects. Concentrations of mRNA for GLUT4, GLUT5, and GLUT12 were much higher than those for the remainder of the GLUTs and together accounted for 98% of the total GLUT isoform mRNA. Immunoblots of muscle homogenates verified that the respective proteins for GLUT4, GLUT5, and GLUT12 were present in normal human muscle. Immunofluorescent studies demonstrated that GLUT4 and GLUT12 were predominantly expressed in type I oxidative fibers; however, GLUT5 was expressed predominantly in type II (white) fibers.
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PMID:Hexose transporter mRNAs for GLUT4, GLUT5, and GLUT12 predominate in human muscle. 1680 53


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