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)

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Cys 149 in the NAD-dependent phosphorylating glyceraldehyde-3-phosphate dehydrogenase from Escherichia coli has been replaced by alanine.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

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

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

We investigated in rat hearts if chronic alcohol consumption causes an enzymatic adaption of the energy-supplying metabolism and/or of the alcohol-aldehyde metabolizing system. 16 rats were pair-fed with a liquid diet for 10 weeks. Ethanol was added to this diet to amount for 35% of calories in eight rats and was isocalorically replaced by saccharose in the control group. Selected enzyme activities of the glycolysis, the glycogenolysis, the beta-oxidation of fatty acids, the citric acid cycle and the alcohol-aldehyde oxidizing system were determined in the supernatants of the homogenized hearts. The intracellular redox state was assessed by measurement of the myocardial nicotinamide coenzymes. Enzyme activities of the alcohol-aldehyde metabolizing system did not alter after chronic alcohol intake. As we found that the capacity to oxidize acetaldehyde was much higher than the ability to oxidize ethanol we must question the role of acetaldehyde in inducing alcoholic cardiomyopathy. Chronic ethanol treatment significantly increased the activity of glyceraldehyde-3-phosphate dehydrogenase and decreased the activity of glycogen phosphorylase. The impairment of the hydroxyacylCoA dehydrogenase was not significant. The other measured enzyme activities did not alter, nor the intracellular redox state. The enzymatic adaption indicates an impaired glycogenolysis, an increased glycolysis, and probably a diminished beta-oxidation of fatty acids. We expect that the measurement of the responding enzyme activities in human endomyocardial biopsies should be a good tool to further classify cardiomyopathies according to biochemical criteria.
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PMID:The effect of chronic ethanol consumption on enzyme activities of the energy-supplying metabolism and the alcohol-aldehyde oxidizing system in rat hearts. 654 83

A number of NAD+ analogs have been tested in their ability to form fluorescent derivatives when UV irradiated with the active site Cys-149 carboxymethylated GAPDH and this has been compared with their properties of acting as hydrogen acceptors and forming the Racker band. Among the analogs tested, NHD+, NGD+, APAD+ and epsilon NAD+ give positive results in all the above-mentioned reactions whereas alpha NAD+, NMN+ and CPAD+ are all negative. FPAD+ forms a fluorescent derivative on UV irradiation with the carboxymethylated enzyme but is inactive as a hydrogen acceptor and does not form the Racker band. This is probably due to thiohemiacetal formation of the pyridine 3-aldehyde of this derivative with the active site SH group required for both the latter 2 reactions. TPAD+, although active active as a hydrogen acceptor, does not form either a fluorescent derivative or a Racker band. The fact that for the great majority of the analogs, the property of forming fluorescent derivatives is in parallel with their hydrogen acceptor activity seems to show that the formation of the fluorescent derivative is indeed at the active site, and hence can be used as an intrinsic probe for the study of the conformation of the active site of this enzyme.
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PMID:NAD+ analogs in formation of new fluorophores on ultraviolet irradiation with D-glyceraldehyde-3-phosphate dehydrogenase. 710 Aug 95

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

Endogenous saturated and unsaturated aldehydes were found in significant elevations in serum of diabetic humans and rats. These compounds, originating from the lipid peroxidation processes, are shown here to be potent inhibitors of the glycolytic enzymes, phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase. The inhibition process is non-competitive and progressive. The aldehyde mixture, when supplemented to the standard rat diet at 1/100 ratio, caused nerve damage that is reminiscent of diabetic polyneuropathies.
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PMID:Inhibition of glycolytic enzymes by endogenous aldehydes: a possible relation to diabetic neuropathies. 820 61

The 4-electron oxidoreductase L-histidinol dehydrogenase (HDH, EC 1.1.1.23) oxidizes the amino alcohol histidinol to histidine via an aldehyde-level intermediate at a single active site. The enzyme contains two Zn2+ per dimer, and treatment with metal chelators causes a metal-reversible inactivation. NAD-linked aldehyde oxidations, for which glyceraldehyde-3-phosphate dehydrogenase has served as the major paradigm, are thought to proceed via cysteine-based thiohemiacetals. Sequenced forms of HDH contain two conserved cysteine residues, Cys-116 and Cys-153 in the Salmonella typhimurium enzyme, and in previous work we have shown that HDH is inactivated by active site modification of Cys-116 by the reagent 4-nitro-7-chlorobenzadioxazole. Thus, Cys-116 is an excellent candidate for the active site nucleophile in HDH. In the current studies we show that treatment of HDH with the Zn2+ chelator 1,10-phenanthroline exposes Cys-116 to specific modification by iodoacetate, resulting in irreversible loss of activity. Site-specific mutagenesis was used to explore the roles of the conserved cysteine residues. The mutant enzymes C116S, C153S, C116A, and C153A and the double mutant C116,153A were each overproduced and purified to homogeneity. All mutant enzymes showed normal kcat and Km values for catalysis. The double mutant protein was unstable, and the single mutants also lose significant activities over a 3-h period during which wild-type enzyme retains full activity. The C116S mutant, and to a lesser extent the C116A mutant, were sensitive to the presence of EDTA in the assay medium, but the other mutants or wild-type enzyme were not, suggesting that Cys-116 may be near, but probably not liganded to, the bound metal ion. The results clearly indicate that HDH does not use a cysteine-based thiohemiacetal as a catalytic intermediate, requiring a new paradigm for NAD-linked aldehyde oxidation. Some models for the reaction are presented and discussed.
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PMID:Conserved cysteine residues of histidinol dehydrogenase are not involved in catalysis. Novel chemistry required for enzymatic aldehyde oxidation. 831 84


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