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PubMedDate not supplied

[Effect of starvation and diabetes on the activity of glucose-6-phosphate and 6-phosphogluconate dehydrogenases and on the free fatty acid content of rat kidney cortex and medulla].

Activity of dehydrogenases related to pentosephosphate pathway was not distinctly altered in soluble fraction of kidney cortex and medulla after 48 and 72 hrs of starvation. In diabetes the activity of these enzymes in rat kidney, as distinct from liver tissue, was not decreased but it was elevated and within 72 hrs after administration of alloxan the activity of glucose-6-phosphate dehydrogenase was increased 2-fold and the activity of 6-phosphogluconate dehydrogenase was increased by 30% above the normal level. Content of free fatty acids was also increased in kidney cortex of diabetic rats within 72 hrs after administration of alloxan. Alterations in content of free fatty acids were not observed either in kidney of diabetic animals within other studied periods (6 and 14-16 days) of treatment or in the tissue of starved rats. The data obtained suggest that free fatty acids do not participate immediately in controlling effect on dehydrogenases of pentosephosphate pathway in kidney in vivo.

Animals↗

PubMed1981

Biochemical genetics of Fundulus heteroclitus (L.). III. Inheritance of isocitrate dehydrogenase (Idh-A and Idh-B), 6-phosphogluconate dehydrogenase (6-Pgdh-A), and serum esterase (Est-S) polymorphisms.

Starch gel electrophoresis has shown that natural populations of Fundulus heteroclitus have variants at four enzyme-coding loci: Idh-A, Idh-B, 6-Pgdh-A, and Est-S. Analysis of the phenotypic distribution of the F1 generation suggests that each of the variants segregates as autosomally inherited codominant alleles. Tissue specificity and intracellular localization were also determined for the IDH and 6PGDH isozymes.

Alleles↗

PubMed1987

[Demonstration of an NAD-dependent 6-phosphogluconate dehydrogenase in Pseudomonas syringae pv. phaseolicola].

Crude extracts from cells of Pseudomonas syringae pv. phaseolicola, a fluorescent pseudomonad, when grown on glucose contain a NAD-linked 6-phosphogluconate dehydrogenase. The reaction of the enzyme, which produces 14CO2 from 1-14C-6-phosphogluconate, is not inhibited by NaF, a potent inhibitor of the Enter-Doudoroff (ED) pathway enzyme 6-phosphogluconate dehydratase. In the presence of phosphate or arsenate ions the NAD-linked glyceraldehyde-3-phosphate dehydrogenase reacts with glyceraldehyde-3-phosphate which, in the ED pathway, is produced from 6-phosphogluconate and overlaps the 6-phosphogluconate dehydrogenase reaction. Only a small proportion of glucose is metabolized via the 6-phosphogluconate dehydrogenase/oxidative pentose phosphate pathway.

Kinetics↗

PubMed1969

Purification and properties of 6-phosphogluconate dehydrogenase from sheep liver.

A method is described for the isolation of 6-phosphogluconate dehydrogenase from sheep liver. The product appears to be homogeneous in polyacrylamide-gel electrophoresis and in sedimentation-velocity and sedimentation-equilibrium studies in the ultracentrifuge. The molecular weight is estimated as 129000 from equilibrium sedimentation.

Acrylates↗

PubMed1975

Purification and properties of an NADP-specific 6-phosphogluconate dehydrogenase from Streptococcus faecalis.

A procedure is described for the purification of 6-phosphogluconate dehydrogenase (6-phospho-D-gluconate:NADP oxidoreductase (decarboxylating) EC 1.1.1.44) from cell extracts of Streptococcus gaecalis. A 180-fold purification was achieved with an over-all yield of about 12% and an average specific activity of 14. The enzyme was homogeneous as determined by polyacrylamide gel electrophoresis, immunoelectrophoresis, and sedimentation equilibrium, studies. Its weight average molecular weight, as measured by sedimentation equilibrium, was 108,000 +/- 3,600. Other methods employed for molecular weight determinations gave values that ranged between 106,000 and 115,000. An analysis of the enzyme by sodium dodecyl sulfate polyacrylamide gel electrophoresis showed it to be a dimer composed of subunits having equal molecular weight. The amino acid composition of the streptococcal enzyme is reported. The apparent Km values for NADP and 6-phosphogluconate were calculated from kinetic data and found to be 0.015 mM and 0.024 mM, respectively. Kinetic studies also indicated that the binding of one substrate did not affect the apparent affinity of the enzyme for the other substrate.

Amino Acids↗

PubMedDate not supplied

Glyoxylate for affinity labelling of 6-phosphogluconate dehydrogenase.

In order to find a new reagent for the affinity labelling, 6-phosphogluconate dehydrogenase was treated with glyoxylate, a versatile metabolite with a carboxyl and a reactive aldehydic group. High concentrations of glyoxylate inhibit the enzyme, while in the presence of the reducing agent cyanoborohydride, the enzyme is irreversibly inactivated by only millimolar glyoxylate. This indicates the formation of a Schiff base between the aldehydic group of glyoxylate and one enzyme lysine residue. The kinetics and substrate competition suggest that inactivation is due to affinity labelling. In the first step the inhibitor carboxylic group binds to the substrate carboxyl binding site, and in the second slower step the aldehydic group binds a nearby lysine. We have also found that other enzymes are inactivated by the combined actions of glyoxylate and cyanoborohydride, with a saturation kinetics. Hence, glyoxylate can be helpful to identify specific lysines at the carboxyl binding sites in proteins.

Affinity Labels↗

PubMed1976

Dietary regulation of 6-phosphogluconate dehydrogenase synthesis.

The relative rates of synthesis and degradation for rat liver 6-phosphogluconate dehydrogenase have been determined in animals maintained at several dietary states. Relative rates of synthesis were determined by pulse-labeling the enzyme either in live rats and determining the radioactivity in the purified enzyme or in whole cell suspensions of hepatocytes followed by precipitation of the enzyme with a specific antiserum. The relative rate of synthesis of the enzyme in rats fed a high carbohydrate fat-free diet was approximately 3.7 to 5.6 times greater than that in animals fed a pellet diet or in fasted rats, respectively. In contrast, a half-life of 13 to 19 hours was determined for the degradation of the enzyme in all three nutritional states. We have concluded that nutritional alterations in the levels of this enzyme in rat liver are caused by alterations in the rate of enzyme synthesis. Glucagon has no effect on the rate of synthesis of this enzyme.

Animals↗

PubMed1986

Genetics of esterases and 6-phosphogluconate dehydrogenase in the Anopheles maculatus complex.

Electromorphic variation for some esterases and 6-phosphogluconate dehydrogenase enzymes in the Anopheles maculatus complex is controlled by four loci which are unlinked to sex. Esterase loci are linked to each other: Est-1-36%-Est-4-16.5%-Est-3; but unlinked to Pgd-2. Linkage data were obtained by selfing the F1 generation from selected parents and analysing genotypes in the F2; the classical dihybrid-cross. The analysis consists of testing observed data for goodness of fit to a) ratios expected from Mendelian ratios without linkage and b) if they do not fit then computing a likely degree of linkage and computing expected ratios with such linkage for further tests. Confidence limits are given for the most likely levels of linkage. This method can provide useful information for population-genetic studies on anopheline mosquitoes, whose laboratory rearing is generally difficult. Through indirect evidence, the enzyme loci are correlated to polytene chromosomes. The esterases probably lie on chromosome three (polytene arms 3 and 4) and Pgd-2 on the second chromosome (arms 2 and 5).

Animals↗

PubMed1998

Cloning, expression, purification, and characterization of the 6-phosphogluconate dehydrogenase from sheep liver.

The mRNA encoding the 51-kDa subunit of 6-phosphogluconate dehydrogenase (6PGDH) from sheep liver was reverse-transcribed and amplified. The resulting cDNA was reamplified in N-terminal and C-terminal segments and spliced to generate a full-length clone, and an internal cDNA fragment was also amplified. The full-length clone containing the complete coding sequence of the 6PGDH cDNA was sequenced and found to contain two mutations and two deletions in the internal region and two mutations outside of the internal region, an A to G point mutation at position 1407 that resulted in the amino acid change Gln 445 to Arg and a silent mutation at position 1426. The internal clone was sequenced and shown to be free of any mutations; therefore the internal piece was used to replace the same region in the full-length clone to correct the mutations in this region. The mutation at position 1407 which was outside of the internal region was corrected using site-directed mutagenesis. The cDNA with the correct codon was then subcloned into the bacterial expression vector pQE-30 and overproduced in Escherichia coli strain M15. A protein with a subunit molecular weight of 51,000 was expressed at a level of about 4.5% of the total soluble protein in M15 as judged by SDS/PAGE. Cloning into pQE-30 adds six histidines and a short linker to the N-terminus of the enzyme. The recombinant 6PGDH with His-tag was purified using the Ni-NTA affinity column supplied by Qiagen. The purification procedure resulted in a homogeneous protein by SDS/PAGE with 22.4-fold purification with an overall yield of 61%. The recombinant enzyme exhibits kinetic parameters within error identical to those measured for native sheep liver enzyme.

Animals↗

PubMed1984

Opposite changes with age in liver and muscle in the mitochondrial and soluble glucose-1,6-bisphosphate and 6-phosphogluconate dehydrogenase.

Glucose-1,6-bisphosphate (Glc-1,6-P2), the powerful regulator of carbohydrate metabolism, was markedly decreased in liver of adult rats (2 months of age) as compared to young rats (1-2 weeks of age). This regulator was found to be present in both the mitochondrial and soluble fractions of liver. Its concentration in both these fractions was decreased with age. Concomitant to the decrease in Glc-1,6-P2, which is a potent inhibitor of 6-phosphogluconate dehydrogenase, the activity of this enzyme was markedly increased with age in both the mitochondrial and soluble fractions. However, the increase in this enzyme's activity was more pronounced in the mitochondrial fraction. The mitochondrial enzyme was more susceptible to inhibition by Glc-1,6-P2 as compared to the soluble enzyme, and this may explain the greater enhancement in its activity with age in this fraction. The tibialis anterior muscle exhibited changes with age opposite to those found in liver; Glc-1,6-P2 concentration, in both the mitochondrial and soluble fractions of muscle increased with age, and this increase was accompanied by a concomitant reduction in the activity of the mitochondrial and soluble 6-phosphogluconate dehydrogenase. Similar to liver, the mitochondrial enzyme was more affected by age, as it also exhibited a greater susceptibility to inhibition by Glc-1,6-P2.

Aging↗

PubMed1977

Investigations on the organization of genetic loci in Drosophila melanogaster: lethal mutations affecting 6-phosphogluconate dehydrogenase and their suppression.

The molecular nature of lethal and semilethal mutations in the Pgd locus of D. melanogaster coding for 6-phosphogluconate dehydrogenase (6PGD) was studied. All the 11 mutations affect the structural gene of the Pgd locus: 3 semilethal mutations resulted in altered 6PGD molecules with decreased catalytic activities; the rest 8 lethals were "null" alleles characterized by mutant polypeptides capable of reacting with antisera against highly purified 6PGD. "Null" or low activity alleles for glucose-6-phosphate dehydrogenase induced by ethyl methanesulfonate were shown to be suppressores for the lethal mutations in the Pgd locus. A monocistronic type of organization of the Pgd locus is suggested taking into account the biochemical mechanism of suppression of the Pgd-lethals and their location in the structural gene coding for 6PGD.

Animals↗

PubMed2003

The treatment of Plasmodium falciparum-infected erythrocytes with chloroquine leads to accumulation of ferriprotoporphyrin IX bound to particular parasite proteins and to the inhibition of the parasite's 6-phosphogluconate dehydrogenase.

Ferriprotoporphyrin IX (FPIX) is a potentially toxic product of hemoglobin digestion by intra-erythrocytic malaria parasites. It is detoxified by biomineralization or through degradation by glutathione. Both processes are inhibited by the antimalarial drug chloroquine, leading to the accumulation of FPIX in the membranes of the infected cell and their consequent permeabilization. It is shown here that treatment of Plasmodium falciparum-infected erythrocytes with chloroquine also leads to the binding of FPIX to a subset of parasite proteins. Parasite enzymes such as aldolase, pyrimidine nucleaside monophosphate kinase and pyrimidine 5'-nucleotidase were inhibited by FPIX in vitro, but only the activity of 6-phosphogluconate dehydrogenase was reduced significantly in cells after drug treatment. Additional proteins were extracted from parasite cytosol by their ability to bind FPIX. Sequencing of these proteins identified heat shock proteins 90 and 70, enolase, elongation factor 1-alpha, phoshoglycerate kinase, glyceraldehyde 3-phosphate dehydrogenase, L-lactate dehydrogenase and gametocytogenesis onset-specific protein. The possible involvement of these proteins in the antimalarial mode of action of chloroquine is discussed. It is concluded that drug-induced binding of FPIX to parasite glycolytic enzymes could underlie the demonstrable inhibition of glycolysis by chloroquine. The inhibition of 6-phosphogluconate dehydrogenase could explain the reduction of the activity of the hexose monophosphate shunt by the drug. Inhibition of both processes is deleterious to parasite survival. Binding of FPIX to other proteins is probably inconsequential to the rapid killing of the parasite by chloroquine.

Animals↗

PubMedDate not supplied

[Purification and some properties of electrophoretic variants of 6-phosphogluconate dehydrogenase from rat erythrocytes].

Purification procedure of electrophoretic variants FF and SS of 6-phosphogluconate dehydrogenase (6-PGD) is described. The method includes (NH4)2SO4 fractionation and chromatography on DEAE- and CM-celluloses. Isoenzymes were purified about 5000 fold, and were found to be homogenous by disc electrophoresis in 7% polyacrylamide gel. It was found by comparative studies of activities of variants FF and SS, that pH optimum was 8.2 for variant FF and 8.8 for variant SS. Km for 6-phosphogluconate were found to be 17,5-10(-5) M for variants SS and FF respectively.

Animals↗

PubMed1993

The 2'-phosphate of NADP is critical for optimum productive binding to 6-phosphogluconate dehydrogenase from Candida utilis.

Initial velocity studies obtained with alternative dinucleotide substrates for the 6-phosphogluconate dehydrogenase reaction suggest that the 2'-phosphate is critical for the optimum productive binding of the dinucleotide substrate. Initial velocity patterns obtained by varying 6-phosphogluconate at different fixed levels of NAD are nearly parallel with apparent competitive substrate inhibition by 6-phosphogluconate at pH 7 and below but intersect to the left of the ordinate at pH 8 and above. Dead-end inhibition studies indicate that the mechanism is random at all pH values. Data are interpreted in terms of a random mechanism with marked antagonism in the binding of NAD and 6-phosphogluconate at low pH. Deuterium isotope effects on V and V/K for either substrate are equal at pH 8, indicating that the kinetic mechanism is rapid equilibrium random. A decrease in the pH and the subsequent protonation of the active site general base or some other enzyme residue with a similar pK apparently results in the ineffective binding of NAD. The latter suggests either a link between the protonation state of this group and the conformation of the dinucleotide binding site or an interaction between the two.

Candida↗

PubMed1991

The structure of 6-phosphogluconate dehydrogenase refined at 2.5 A resolution.

The three-dimensional structure of ovine 6-phosphogluconate dehydrogenase, refined at 2.5 A resolution with a residual for all data of 18.5%, is reported. This model, based on improved diffraction data and a corrected sequence, supersedes that reported earlier. Each subunit of the dimer has three domains: a beta-alpha-beta domain binds NADP; an all alpha domain provides much of the dimer interface; the C-terminal tail burrows into the second subunit.

Molecular Structure↗

PubMed1983

The three dimensional structure of sheep liver 6-phosphogluconate dehydrogenase at 2.6 A resolution.

The three-dimensional structure of sheep liver 6-phosphogluconate dehydrogenase has been determined at 2.6 A resolution by X-ray crystallographic studies. The amino acid sequence of the enzyme is now known and can be fitted to a modified electron density map. Use of 6 A electron density maps and the results of chemical modification experiments allows description of the active site and identification of residues which may be implicated in the binding of co-enzyme and substrate.

Animals↗

PubMed1984

Specific deletion occurring in the directed evolution of 6-phosphogluconate dehydrogenase in Escherichia coli.

A novel genetic change leading to increased activity of 6-phosphogluconate dehydrogenase (6PGD) in E. coli has been observed. The mutation is a deletion of approximately 0.4 kilobase pairs occurring between the structural gene of 6PGD (gnd) and one copy of an insertion element (IS5) found normally in E. coli K12 a few hundred base pairs upstream (counterclockwise) from gnd at 44 minutes on the conventional genetic map. The deletion is associated with a threefold higher activity of 6PGD and a 57% increase in the maximum growth rate when cells are grown in gluconate.

Bacterial Proteins↗

PubMed1975

Lethal effects of low and "null" activity alleles of 6-phosphogluconate dehydrogenase in Drosophila melanogaster.

EMS-induced "null" and low activity alleles for 6-phosphogluconate dehydrogenase were characterized with respect to enzymatic activity, relative viability, fertility, and the effective lethal phase. It was determined that flies hemizygous and homozygous for the low activity allele, Pgd minus, possessed a depressed development rate, diminished viability, and loss of female female fertility. Heterozygotes for Pgd minus and a deficiency for Pgd+ were lethal. The "null" activity allele demonstrated a lethal phenotype in both the hemizygous and homozygous condition. The effective lethal phase for the "null" allele occurs during late embryonic development (20-22 hr).

Alleles↗