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)

NAD-Sepharose 4B gel was used to study the complexation between glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating) EC 1.2.1.12) and aldolase (D-fructose-1,6-bisphosphate D-glyceraldehyde-3-phosphate-lyase, EC 4.1.2.13). An affinity sorbent specific for glyceraldehyde-3-phosphate dehydrogenase was utilised in a batch system. The dissociation constant of the enzyme complex was calculated. The method elaborated in our laboratory was used to investigate the effects of temperature and pH on the complex formation.
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PMID:Characterization of enzyme-enzyme interaction using an affinity batch system. 710 69

Platelet-derived growth factor (PDGF)-BB stimulates fibroblast-mediated contraction of collagen gels, as well as migration of fibroblasts through collagen-coated membranes. In the present study we examined effects of PDGF-BB stimulation on the synthesis of collagen-binding beta 1 integrins by human diploid fibroblasts (AG 1518). PDGF-BB stimulation led to an increase in the rare of integrin alpha 2-subunit synthesis. In contrast, synthesis of the integrin alpha 1- or alpha 3-subunits were not affected by PDGF-BB stimulation. Furthermore, levels of alpha 2-subunit mRNA relative to levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA increased after PDGF-BB stimulation. The latter finding is compatible with PDGF-BB stimulating transcription of the alpha 2-subunit gene. PDGF-BB stimulation did not influence the relation between levels of integrin beta 1-subunit mRNA and GAPDH mRNA. In addition, the rate of synthesis or post-translational processing of the integrin beta 1-subunit were not, or only marginally, affected by PDGF-BB stimulation. It is likely that the motility response elicited in fibroblasts by PDGF-BB involves such alterations in the synthesis of the alpha 2-subunit of the alpha 2 beta 1 collagen-binding integrin.
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PMID:Platelet-derived growth factor-BB stimulates synthesis of the integrin alpha 2-subunit in human diploid fibroblasts. 752 96

Nitric oxide signaling is achieved through cGMP-dependent and -independent mechanisms. The latter are exemplified by the NAD(+)-dependent automodification of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The experimental post-translational, covalent modification of the enzyme by [32P]NAD+ is achieved using NO-releasing compounds and an active constitutive or inducible NO-synthase. Potential roles for NO in this covalent enzyme modification can be grouped as follows: S-Nitrosylation of GAPDH by NO+ NAD(+)-dependent, post-translational covalent automodification of GAPDH. Oxidative modification of GAPDH by NO-related compounds, probably ONOO. GAPDH modification by one of the proposed mechanisms would lead to inhibition of enzyme catalysis. It is likely that the NAD(+)-dependent automodification process occurs in vitro, in intact cells, and in whole animals. Besides its normal function in glycolysis, GAPDH not only is a target for NO-mediated direct and indirect modifications but also is ADP-ribosylated in the presence of brefeldin A (90). The relation of such ADP-ribosylation to enzyme activity is so far unknown. GAPDH also may be involved in one of the following functions unrelated to its glycolytic activity (81 and refs. therein; 90): binding and transport of tRNA associated with nuclear localization of GAPDH. DNA-repair activity, i.e., uracil DNA glycosylase. Activation of transcription in neurons. Interaction with tubulin and microtubules. The transport of nitric oxide. Serves as a substrate for brefeldin A stimulated ADP-ribosylation. Because some of these alternative functions of GAPDH, just like NO-mediated modification of the enzyme, are related to the NAD+ binding site of the protein, we are interested in searching for the significance of these activities in relation to NO actions. In recent years, several functions of NO have been linked to direct, cGMP-independent actions. Modification of GAPDH is probably just one interesting target related to NO-redox chemistry and active-site thiol modification. It will be challenging to investigate NO biochemistry in closer detail and to elucidate how NO targets biological systems, especially in relation to the patho-physiological role of NO in medically related conditions.
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PMID:Protein thiol modification of glyceraldehyde-3-phosphate dehydrogenase as a target for nitric oxide signaling. 754 26

Non-phosphorylating glyceraldehyde 3-phosphate dehydrogenase (GAPDH, NADP-specific, EC 1.2.1.9) operates in the cytosol of autotrophic eukaryotes where it generates NADPH for biosynthetic processes from photosynthetic glyceraldehyde 3-phosphate exported from the chloroplast by the phosphate translocator. Here we report the first cloning and characterization of cDNAs encoding complete polypeptide chains of nonphosphorylating GAPDH from pea and maize by using oligonucleotide probes derived from amino acid sequences determined for the purified enzyme. Unexpectedly, nonphosphorylating GAPDH cannot be aligned with the well-known sequences of phosphorylating GAPDH, but shares about 30% amino acid identity with various specialized and non-specialized aldehyde dehydrogenases (ALDHs) of eubacteria and eukaryotes. A phylogenetic analysis of this ALDH superfamily reveals a complex evolutionary pattern with numerous major branches carrying genes from eubacteria, eukaryotes, or both, encoding enzymes that are specific or non-specific for particular aldehyde substrates. This topology suggests a concomitant emergence of multiple substrate specificities from non-specialized ALDH during an early evolutionary phase of intense metabolic diversification. Although unrelated at the sequence level, non-phosphorylating aldehyde dehydrogenases and phosphorylating GAPDH resemble one another with respect to catalytic hydride transfer and covalent thiol ester formation. Whether or not this reflects an ancestral relationship can only be decided when crystallographic data for ALDH enzymes have become available.
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PMID:Non-phosphorylating GAPDH of higher plants is a member of the aldehyde dehydrogenase superfamily with no sequence homology to phosphorylating GAPDH. 754 14

In this study, we have investigated the effect of fibroblast growth factors (bFGF and FGF-5) and brain derived neurotrophic factor (BDNF) on the expression of calcitonin gene-related peptide (CGRP) in rat motoneurons in vivo and in vitro. Following sciatic nerve transection in adult rats, the levels of alpha-CGRP and beta-CGRP mRNA were up- and down-regulated respectively in axotomized motoneurons, revealed by in situ hybridization histochemistry. Local administration of 1 microgram bFGF was able to entirely abolish the up-regulation of alpha-CGRP mRNA, and to further down-regulate beta-CGRP. These effects, albeit less pronounced, were still evident with 0.2 micrograms bFGF. In contrast, bFGF did not attenuate the lesion-induced decrease of choline acetyltransferase (ChAT) mRNA. Administration of BDNF did not significantly alter the expression of CGRP or ChAT mRNA in axotomized motoneurons. Both alpha- and beta-CGRP mRNAs could be detected by PCR in enriched motoneuron cultures prepared from rat embryos at embryonic day 14-15. Comparing the amplification of alpha- and beta-CGRP mRNAs with that of mRNA encoding glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in parallel samples, we found that cultures treated with FGF-5 had a lower ratio of alpha- and beta-CGRP mRNA to GAPDH mRNA, than did control or BDNF-treated cultures. BDNF, on the other hand increased alpha-CGRP and decreased beta-CGRP mRNA levels, though these effects were moderate compared with the effects of FGF-5. The results obtained in this study suggest that members of the FGF family of growth factors influence the expression of CGRP in rat motoneurons, and that the increase of this neuropeptide induced by axotomy may, at least in part, be due to deprivation of these target-derived factors.
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PMID:Fibroblast growth factors regulate calcitonin gene-related peptide mRNA expression in rat motoneurons after lesion and in culture. 758 27

The objective of the present study was to quantify the expression of angiotensin II type 1 (AT1) receptor transcripts in human blood cells--platelets and mononuclear leukocytes--from 10 normal healthy volunteers during the alterations in the renin-angiotensin system. A quantitative assay employing reverse transcription-polymerase chain reaction (RT-PCR) was utilized. Oral administration of furosemide, 40 mg for 2 days, under mild salt restriction (50 mEq NaCl/day) for 6 days stimulated the renin-angiotensin system resulting in significant increases in plasma renin activity (PRA) (1.84 +/- 0.12 vs. 1.05 +/- 0.17 ng/l/s; P < 0.01), plasma angiotensin II concentration, and plasma aldosterone concentration (PAC). The ratio of AT1 receptor mRNA to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA expression in mononuclear leucocytes was significantly (P < 0.05) increased from the basal level (0.49 +/- 0.05 vs. 0.29 +/- 0.03) (P < 0.01), while in platelets these changes were opposite (0.11 +/- 0.05 vs. 0.25 +/- 0.05) (P < 0.01). Compared to these significant changes, salt loading (200 mEq NaCl/day) for 6 days decreased PRA(0.49 +/- 0.10 vs. 1.05 +/- 0.17 ng/l/s; P < 0.01) and induced the opposite changes in the ratio of AT1 receptor/GAPDH mRNA. These data suggest that AT1 receptors in human blood cells may be of two different types--platelets and mononuclear leucocytes.
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PMID:Modulation of angiotensin II type 1 receptor mRNA expression in human blood cells: comparison of platelets and mononuclear leucocytes. 759 93

A 37 kDa protein that binds to diadenosine tetraphosphate (Ap4A) was purified from human HeLa cells and identified as uracil DNA glycosylase/glyceraldehyde-3-phosphate dehydrogenase (UDG/GAPDH). Utilizing photoaffinity labeling with [alpha-32P]8N3-Ap4A, an Ap4A binding protein of 37 kDa was identified from HeLa cell nuclear extracts. The 37 kDa protein was purified to homogeneity and subjected to trypsin digestion followed by amino acid sequence analysis. Two peptide sequences were determined and both had complete identity with the amino acid sequence of the 37 kDa polypeptide of UDG/GAPDH. Purified UDG/GAPDH binds to Ap4A with the same affinity as the HeLa cell nuclear 37 kDa Ap4A binding protein, and monoclonal antibodies to UDG/GAPDH cross-react with the 37 kDa Ap4A binding protein. UDG/GAPDH has been previously demonstrated to have numerous nonglycolytic activities. The UDG function is involved in DNA repair by excision of uracil from DNA. GAPDH is a RNA binding protein and binds to tRNA and AU-rich RNA. The AU-rich RNA binding has been implicated in the regulation of AU-rich element dependent mRNA turnover and translation. The identification of UDG/GAPDH as an Ap4A binding protein may be physiologically relevant to the proposed role of Ap4A as a regulatory nucleotide in cell growth.
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PMID:Uracil DNA-glycosylase/glyceraldehyde-3-phosphate dehydrogenase is an Ap4A binding protein. 762 40

A circularly permuted (cp) variant of the phosphorylating NAD-dependent glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from Bacillus stearothermophilus has been constructed with N- and C-termini created within the coenzyme binding domain. The cp variant has a kcat value equal to 40% of the wild-type value, whereas Km and KD values for NAD show a threefold decrease compared to wild type. These results indicate that the folding process and the conformational changes that accompany NAD binding during the catalytic event occur efficiently in the permuted variant and that NAD binding is tighter. Reversible denaturation experiments show that the stability of the variant is only reduced by 0.7 kcal/mol compared to the wild-type enzyme. These experiments confirm and extend results obtained recently on other permuted proteins. For multimeric proteins, such as GAPDH, which harbor subunits with two structural domains, the natural location of the N- and C-termini is not a prerequisite for optimal folding and biological activity.
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PMID:Circular permutation within the coenzyme binding domain of the tetrameric glyceraldehyde-3-phosphate dehydrogenase from Bacillus stearothermophilus. 766 55

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH, EC 1.2.1.12) activity and mRNA content is altered in the androgen-responsive human prostate carcinoma cell line LNCaP after exposure to the synthetic androgen R1881. Elevation in GAPDH activity is noted as early as 24 h after treatment with 1 nM R1881 and lasts at least 96 h. R1881 has no effect on the activity of GAPDH in androgen-independent DU145 cells. LNCaP GAPDH mRNA content is lowered by treatment with 1 nM R1881; the magnitude of reduction appears to depend on the length of exposure. The results present at least one means by which androgen-responsive tissues may develop alterations in GAPDH mRNA or activity, as is found in certain tumor tissues.
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PMID:Alteration of glyceraldehyde-3-phosphate dehydrogenase activity and messenger RNA content by androgen in human prostate carcinoma cells. 767 Dec 26

Nitric oxide (NO) or NO-generating compounds like sodium nitroprusside (SNP) increase cellular levels of cGMP and produce S-nitrosylation of glyceraldehyde-3-phosphate dehydrogenase [GAPDH; D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12]. In search of a reagent that could discriminate between these two effects, we used the sesquiterpene antibiotic koningic acid, which binds to GAPDH at the Cys-149 of the active site. Koningic acid inhibited basal and sodium nitroprusside-stimulated NAD-dependent covalent modification of purified rabbit muscle GAPDH in a dose-dependent manner. Furthermore, we tested the effect of koningic acid on human platelets. Approximately 90% of GAPDH is present in the cytosol of human platelets, and the exposure of platelet cytosol to koningic acid inhibited GAPDH activity, while the soluble guanylyl cyclase (basal and sodium nitroprusside-stimulated) activity remained unaltered. Pretreatment of intact platelets with koningic acid slowed the rate of aggregation induced by a submaximal concentration of thrombin. In addition, the antibiotic also inhibited the cGMP increases triggered by SNP, S-nitroso-N-acetylpenicillamine (SNAP), and 3-morpholinosyndomidine (SIN-1) but failed to prevent an increase in cGMP caused by nitrosylated albumin. Under the same conditions, koningic acid also inhibited basal and SNP- SNAP-, and SIN-1-stimulated NAD-dependent modification of GAPDH and its enzymatic activity. These results suggest that the mechanism of delivery of NO from SNP, SNAP, and SIN-1 to platelets may require the active form of GAPDH. When NO is delivered by nitrosylated albumin, active GAPDH was not necessary.
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PMID:Glyceraldehyde-3-phosphate dehydrogenase is required for the transport of nitric oxide in platelets. 790 82


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