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)

[omega-(3-Acetylpyridinio)-n-alkyl]adenosine pyrophosphates are coenzyme analogs of NAD. The adenosine pyrophosphate moiety and the 3-acetylpyridine ring of the analogs are connected by n-alkyl chains of different lengths (ethyl--hexyl). The analogs form strong dissociating complexes with lactate dehydrogenase. The complex formation is predominantly achieved by interaction of the ADP moiety with its respective binding domain at the active site. The redox potentials of the analogs and NAD are of similar magnitude. The coenzyme function of the analogs depends upon the length of the hydrocarbon chain. Lactate dehydrogenase and alcohol dehydrogenases from yeast and horse liver do not catalize hydrogen transfer from their substrates to any other alkyl analog but [4-(3-acetylpyridinio)-n-butyl]adenosine pyrophosphate, aldehyde dehydrogenase from horse liver catalizes hydrogen transfer from acetaldehyde to the pentyl derivative and glyceraldehyde-3-phosphate dehydrogenase catalizes hydrogen transfer to both analogs. In no case, hydrogen transfer from or to one of the 3-acetylpyridine-n-alkyl analogs proceeded with a velocity comparable to NAD or its 3-acetylpyridine analog. The results show that the nicotinamide bound ribose in NAD is involved in the binding and the activation of the coenzyme.
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PMID:[The properties of [omega(3-acetylpyridinio)-n-alkyl]adenosine pyrophosphates, structural analogs of the coenzyme NAD (author's transl)]. 19 87

The possibility of interaction between purified rabbit muscle aldolase and D-glyceraldehyde-3-phosphate dehydrogenase was studied by rapid kinetic methods, by analyzing the kinetics of the consecutive reaction catalyzed by the coupled enzyme system. The Km of the intermediary product, glyceraldehyde 3-phosphate, produced by aldolase was determined in the coupled reaction for glyceraldehyde-3-phosphate dehydrogenase. Its value corresponds to that of the aldehyde (active) form of glyceraldehyde 3-phosphate, although in the given conditions the aldehyde leads to diol interconversion is faster than the enzymic reaction catalyzed by glyceraldehyde-3-phosphate dehydrogenase. We suggest that above a certain concentration of the enzymes the glyceraldehyde 3-phosphate produced by aldolase gets direct access to glyceraldehyde-3-phosphate dehydrogenase without participating in the aldehyde leads to diol interconversion which otherwise would occur if the substrate were to mix with the bulk medium.
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PMID:Kinetic evidence for interaction between aldolase and D-glyceraldehyde-3-phosphate dehydrogenase. 20 15

NAD(P) aldehyde dehydrogenases (EC 1.2.1.3) are a family of enzymes that oxidize a wide variety of aldehydes into acid or activated acid compounds. Using site-directed mutagenesis, the essential nucleophilic Cys 149 in the NAD-dependent phosphorylating glyceraldehyde-3-phosphate dehydrogenase from Escherichia coli has been replaced by alanine. Not unexpectedly, the resulting mutant no longer shows any oxidoreduction phosphorylating activity. The same mutation, however, endows the enzyme with a novel oxidoreduction nonphosphorylating activity, converting glyceraldehyde 3-phosphate into 3-phosphoglycerate. Our study further provides evidence for an alternative mechanism in which the true substrate is the gem-diol entity instead of the aldehyde form. This implies that no acylenzyme intermediate is formed during the catalytic event. Therefore, the mutant C149A is a new enzyme which catalyzes a distinct reaction with a chemical mechanism different from that of its parent phosphorylating glyceraldehyde-3-phosphate dehydrogenase. This finding demonstrates the possibility of an alternative route for the chemical reaction catalyzed by classical nonphosphorylating aldehyde dehydrogenases.
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PMID:A new chemical mechanism catalyzed by a mutated aldehyde dehydrogenase. 146 40

Growth inhibition and cell killing caused by sulphite were reduced in seven Saccharomyces cerevisiae sulphite-resistant independent mutants, compared to their parental strains. Genetic analysis showed that in the seven mutants resistance was inherited as a single-gene dominant mutation and that all the analyzed mutations were allelic, thus identifying a major gene responsible for sulphite resistance in S. cerevisiae. Two of the mutants, MBS20-9 and MBS30, were further characterized. 35S-sulphite uptake experiments showed that the ability to accumulate sulphite was markedly reduced in the two resistant strains. No difference between resistant and sensitive strains with respect to glyceraldehyde-3-phosphate dehydrogenase sensitivity to sulphite, or to intracellular glutathione content, were revealed. In contrast, the extracellular acetaldehyde concentration was higher in the resistant mutants, both in the presence and in the absence of sulphite.
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PMID:Mechanism of resistance to sulphite in Saccharomyces cerevisiae. 147 74

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

The gene ald, encoding aldehyde dehydrogenase, has been cloned from a genomic library of Escherichia coli K-12 constructed with plasmid pBR322 by complementing an aldehyde dehydrogenase-deficient mutant. The ald region was sequenced, and a single open reading frame of 479 codons specifying the subunit of the aldehyde dehydrogenase enzyme complex was identified. Determination of the N-terminal amino acid sequence of the enzyme protein unambiguously established the identity and the start codon of the ald gene. Analysis of the 5'- and 3'-flanking sequences indicated that the ald gene is an operon. The deduced amino acid sequence of the ald gene displayed homology with sequences of several aldehyde dehydrogenases of eukaryotic origin but not with microbial glyceraldehyde-3-phosphate dehydrogenase.
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PMID:Molecular cloning and DNA sequencing of the Escherichia coli K-12 ald gene encoding aldehyde dehydrogenase. 191 45

Several enzymes active in the presence of NAD with acetaldehyde and propionaldehyde have been purified from human brain and characterized. The enzymes have been identified as aldehyde dehydrogenase (EC 1.2.1.3), NAD-linked succinic semialdehyde dehydrogenase (EC 1.2.1.24), and glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12). Glyceraldehyde-3-phosphate dehydrogenase is extremely heterogeneous with some isozymes active with acetaldehyde, others inactive. The cytoplasmic enzyme, which is the classical glyceraldehyde-3-phosphate dehydrogenase, is inactive with acetaldehyde as substrate; the isozymes that are active with short chain aliphatic aldehydes are localized in the mitochondrial fraction. Properties of glyceraldehyde-3-phosphate dehydrogenase isozymes with respect to short chain aliphatic aldehydes and inhibition by disulfiram are described. Their Km values for acetaldehyde range from 300 to 2000 microM. All glyceraldehyde-3-phosphate dehydrogenases that are active with acetaldehyde are easily inactivated by low concentrations of disulfiram. In all cases activity regain can be obtained with 2-mercaptoethanol; in the case of two glyceraldehyde-3-phosphate isozymes (E8.5 and 9.0), activity can also be regained with cysteine and with glutathione; activity of E6.6 and E6.8 glyceraldehyde-3-phosphate dehydrogenases could not be regained with 33 microM cysteine or glutathione. Succinic semialdehyde dehydrogenase and aldehyde dehydrogenase (EC 1.2.1.3) were also inhibited by disulfiram; their activity could be regained with 2-mercaptoethanol but not with 33 microM cysteine or glutathione. Comparison of human brain succinic semialdehyde dehydrogenase and aldehyde dehydrogenase with glyceraldehyde-3-phosphate dehydrogenase shows that the activity with short chain aldehydes is not unique to aldehyde dehydrogenase; neither is sensitivity to disulfiram; activity with 3,4-dihydroxyphenylacetaldehyde appears to be a unique property of aldehyde dehydrogenase (EC 1.2.1.3).
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PMID:Human brain glyceraldehyde-3-phosphate dehydrogenase, succinic semialdehyde dehydrogenase and aldehyde dehydrogenase isozymes: substrate specificity and sensitivity to disulfiram. 269 Jun 58

Human and rat O6-methylguanine transferase (O6MeGT) are inhibited in vitro by ethanol at concentrations of 10 to 50 mM and by acetaldehyde, the first metabolite of ethanol, at concentrations as low as 0.01 microM. Several other enzymes, including glyceraldehyde-3-phosphate dehydrogenase and yeast alcohol dehydrogenase, which like O6MeGT have cysteines in their active sites, were not inhibited by acetaldehyde at the levels that inhibited O6MeGT. Disulfiram, an acetaldehyde dehydrogenase inhibitor, enhanced the inhibitory effect of ethanol in vivo. These results indicate that the inhibitory effect of ethanol on O6MeGT activity is mediated primarily via its metabolite, acetaldehyde.
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PMID:In vitro and in vivo inhibitory effect of ethanol and acetaldehyde on O6-methylguanine transferase. 336 37

The reduction of benzaldehyde and p-nitrobenzaldehyde by NADH, catalyzed by horse liver alcohol dehydrogenase (LADH), has been found to be faster when NADH is bound to glyceraldehyde-3-phosphate dehydrogenase (GPDH) than with free NADH. The rate of reduction of aldehyde substrate with GPDH-NADH follows a Michaelian concentration dependence on GPDH-NADH. The reaction velocity is independent of GPDH concentration when [GPDH] greater than [NADH]total. The Km for GPDH-NADH is higher than that for free NADH. The reaction velocities in the presence of excess GPDH over NADH cannot be accounted for on the basis of the free NADH concentration arising from dissociation of the GPDH-NADH complex. These observations suggest that transfer of NADH from GPDH to LADH proceeds through the initial formation of a GPDH-NADH-LADH complex. Arguments for a direct enzyme-coenzyme-enzyme transfer mechanism are substantiated and quantitated both by steady-state kinetic studies and by determinations of all of the appropriate enzyme-coenzyme equilibrium dissociation constants. In contrast, over a similar concentration range, the complex lactate dehydrogenase (LDH)-NADH is not a substrate for the LADH-catalyzed reductions. Likewise, the LADH-NADH complex is not a substrate for the LDH-catalyzed reduction of pyruvate.
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PMID:Direct transfer of reduced nicotinamide adenine dinucleotide from glyceraldehyde-3-phosphate dehydrogenase to liver alcohol dehydrogenase. 638 29

The metabolism of [2-3H]lactate was studied in isolated hepatocytes from fed and starved rats metabolizing ethanol and lactate in the absence and presence of fructose. The yields of 3H in ethanol, water, glucose and glycerol were determined. The rate of ethanol oxidation (3 mumol/min per g wet wt.) was the same for fed and starved rats with and without fructose. From the detritiation of labelled lactate and the labelling pattern of ethanol and glucose, we calculated the rate of reoxidation of NADH catalysed by lactate dehydrogenase, alcohol dehydrogenase and triosephosphate dehydrogenase. The calculated flux of reducing equivalents from NADH to pyruvate was of the same order of magnitude as previously found with [3H]ethanol or [3H]xylitol as the labelled substrate [Vind & Grunnet (1982) Biochim. Biophys. Acta 720, 295-302]. The results suggest that the cytoplasm can be regarded as a single compartment with respect to NAD(H). The rate of reduction of acetaldehyde and pyruvate was correlated with the concentration of these metabolites and NADH, and was highest in fed rats and during fructose metabolism. The rate of reoxidation of NADH catalysed by lactate dehydrogenase was only a few per cent of the maximal activity of the enzymes, but the rate of reoxidation of NADH catalysed by alcohol dehydrogenase was equal to or higher than the maximal activity as measured in vitro, suggesting that the dissociation of enzyme-bound NAD+ as well as NADH may be rate-limiting steps in the alcohol dehydrogenase reaction.
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PMID:The reversibility of cytosolic dehydrogenase reactions in hepatocytes from starved and fed rats. Effect of fructose. 647 25


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