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At least 19 recordsLinked to original sources
PubMed1976

[Variations of various enzymatic activities of the Krebs cycle (malate dehydrogenase, isocitrate dehydrogenase, succinate dehydrogenase) during experimental ischemic shock in the rat. Influence of adenosine 5' triphosphoric acid].

During the ischemic shock caused by the removal of tourniquets placed on the hind paws of the rat, a marked decrease in the enzyme activities of Krebs cycle yielding ATP (malate dehydrogenase, isocitrate dehydrogenase, succinate dehydrogenase) at the level of the gastrocnemius muscle and the liver, was observed together with a plasma increase of these enzymes. The intraperitoneal injection of ATP diminishes significantly the variations observed.

Adenosine Triphosphate↗
PubMed1969

Control of the citric acid cycle by glyoxylate. The mechanism of inhibition of oxoglutarate dehydrogenase, isocitrate dehydrogenase and aconitate hydratase.

1. The effects of glyoxylate on partially purified preparations of aconitate hydratase, isocitrate dehydrogenase and oxoglutarate dehydrogenase were compared with those of oxalomalate and hydroxyoxoglutarate (obtained by condensation of glyoxylate with oxaloacetate and pyruvate respectively). 2. Glyoxylate (1mm) did not affect aconitate hydratase and isocitrate dehydrogenase, whereas oxalomalate (1mm) inhibited the enzyme activities completely. 3. Glyoxylate (0.025mm) inhibited oxoglutarate dehydrogenase irreversibly, whereas the same concentrations of oxalomalate and hydroxyoxoglutarate were ineffective. This inhibitory effect was prevented if oxoglutarate, pyruvate or oxaloacetate was mixed with the enzyme before the glyoxylate. 4. Incubation of oxoglutarate dehydrogenase with radioactive glyoxylate produced radioactive carbon dioxide; radioactivity was also recovered in the portion of the enzyme identified with thiamin pyrophosphate. 5. The behaviour of glyoxylate in producing multiple inhibitions of the citric acid cycle, either by direct interaction with oxoglutarate dehydrogenase, or by means of its condensation compounds which inhibit aconitate hydratase and isocitrate dehydrogenase, is discussed.

Animals↗
PubMed1996

O-Alkyl Hydroxamates as Metaphors of Enzyme-Bound Enolate Intermediates in Hydroxy Acid Dehydrogenases. Inhibitors of Isopropylmalate Dehydrogenase, Isocitrate Dehydrogenase, and Tartrate Dehydrogenase(1).

The inhibition of Thermus thermophilus isopropylmalate dehydrogenase by O-methyl oxalohydroxamate was studied for comparison to earlier results of Schloss with the Salmonella enzyme. It is a fairly potent (1.2 &mgr;M), slow-binding, uncompetitive inhibitor against isopropylmalate and is far superior to an oxamide (25 mM K(i) competitive) that is isosteric with the ketoisocaproate product of the enzyme. This improvement in inhibition was attributed to its increased NH acidity, which presumably is due to the inductive effect of the hydroxylamine oxygen. This principle was extended to the structurally homologous enzyme isocitrate dehydrogenase from E. coli, for which the compound O-(carboxymethyl) oxalohydroxamate is a 30 nM inhibitor, uncompetitive against isocitrate. The pH dependence of its inhibition supports the idea that it is bound to the enzyme in the anionic form. Another recently discovered homologous enzyme, tartrate dehydrogenase from Pseudomonas putida, was studied with oxalylhydroxamate. It has a relatively low affinity for the enzyme, though it is superior to tartrate. On the basis of these leads, squaric hydroxamates with increased acidity compared to squaric amides directed toward two of these enzymes were prepared, and they also show increased inhibitory potency, though not approaching the nanomolar levels of the oxalylhydroxamates.

Journal Article↗
PubMedDate not supplied

[Glucose utilization and activity of glucose-6-phosphate dehydrogenase, isocitrate dehydrogenase and malate dehydrogenase in rat erythrocytes after treatment with tuberculostatic agents].

Metazamide, phthivazid, larusan and rifamycin were shown to inhibit activities of glucose-6-phosphate-, isocitrate- and malate dehydrogenases in male rats within 10-14 days by 14-32%; as a result of this, the rate of glucose consumption was decreased in blood, as shown by the shape of sugar plots after loading with 300 mg of glucose. Administration of these drugs led to elevation of sugar curves by 11-18% as compared with controls. p-Amino-salicylic acid, isoniazid and protionamide inhibited the enzymatic activity but affected the rate of glucose consumption only slightly. Ethambutal activated these enzymes by 13-29%; the highest rate of glucose consumption was observed in presence of the drug.

Animals↗
PubMed1984

The regulatory properties of isocitrate dehydrogenase kinase and isocitrate dehydrogenase phosphatase from Escherichia coli ML308 and the roles of these activities in the control of isocitrate dehydrogenase.

Isocitrate dehydrogenase kinase can use ATP but not other nucleoside triphosphates as a phosphate donor. It responds hyperbolically to both ATP and isocitrate dehydrogenase. The kinase is inhibited sigmoidally by low concentrations of DL-isocitrate and hyperbolically by ADP, AMP, NADPH, phosphoenolpyruvate and several other effectors. Isocitrate dehydrogenase phosphatase requires a nucleotide for activity; ADP and ATP are the best activators. The phosphatase responds hyperbolically to ADP or ATP, to Mg2+ ions and to phosphorylated isocitrate dehydrogenase. The phosphatase is activated twofold to threefold by AMP, oxaloacetate, pyruvate, phosphoenolpyruvate, 2-oxoglutarate and DL-isocitrate. It is inhibited hyperbolically by NADPH. The pH optima and the Km values for substrates of the kinase and the phosphatase are reported. We propose that the role of the phosphorylation of isocitrate dehydrogenase during growth of Escherichia coli on acetate is to render this enzyme rate-limiting in the citric acid cycle; this should cause an increase in the level of isocitrate and divert the flux of carbon through the glyoxylate bypass. We suggest that the phosphorylation state of isocitrate dehydrogenase in intact cells is controlled by the levels of isocitrate, phosphoenolpyruvate, NADPH and the adenine nucleotides. This theory can explain many recent observations on the control of the activity of isocitrate dehydrogenase.

Catalysis↗
PubMed1982

Chromosome localization of the genes for isocitrate dehydrogenase-1, isocitrate dehydrogenase-2, glutathione reductase, and phosphoglycerate kinase-1 in the American mink (Mustela vison).

Twenty-eight hybrid clones with different mink chromosomes were derived from the fusion of Chinese hamster and American mink (mustela vison) cells. This set of clones made it possible to assign the mink genes for isocitrate dehydrogenase-1 (soluble) to chromosome 4, for isocitrate dehydrogenase-2 (mitochrondrial) to chromosome 10, for glutathione reductase to chromosome 6, and for phosphoglycerate kinase-1 to the X chromosome.

Animals↗
PubMed1996

Crystallization and preliminary diffraction analysis of porcine heart mitochondrial NADP(+)-dependent isocitrate dehydrogenase.

Isocitrate dehydrogenases [isocitrate:NAD(P)(+) oxidoreductase (decarboxylating), E.C. 1.1.1.42] are ubiquitous metabolic enzymes which occur in all living organisms. The NADP(+)- dependent mitochondrial isocitrate dehydrogenase from pig heart has been crystallized from polyethylene glycol/sodium sulfate mixtures in the presence of Mg(2+) and isocitrate. The crystals belong to space group C2 with a = 137.0, b = 113.4, c = 65.0 A and beta = 98.5 degrees, and diffract to at least 2.4 A resolution. There are two protein monomers per asymmetric unit which are related by non-crystallographic twofold symmetry.

Journal Article↗
PubMed1977

Alpha-ketoglutarate supply for amino Acid synthesis in higher plant chloroplasts: intrachloroplastic localization of NADP-specific isocitrate dehydrogenase.

Isocitrate dehydrogenase was found in Pisum sativum chloroplasts purified on sucrose density gradients. A chloroplast-enriched pellet obtained by differential centrifugation formed two chlorophyll-containing bands. The lower one containing intact chloroplasts had NADP-specific isocitrate dehydrogenase and triose-phosphate isomerase activities. Mitochondria and peroxisomes were observed to band well away from the intact chloroplast region, as indicated by peak activities of fumarase and catalase, respectively. The presence of isocitrate dehydrogenase in chloroplasts suggests that chloroplasts may generate at least some of the alpha-ketoglutarate required for glutamate synthesis.

Journal Article↗
PubMed2000

Active site water molecules revealed in the 2.1 A resolution structure of a site-directed mutant of isocitrate dehydrogenase.

Isocitrate dehydrogenase catalyses the two step, acid base, oxidative decarboxylation of isocitrate to alpha-ketoglutarate. Lysine 230 was suggested to act as proton donor based on geometry and spatial proximity to isocitrate. To clarify further the role of lysine 230, we co-crystallized the lysine-to-methionine mutant (K230M) with isocitrate and with alpha-ketoglutarate. Crystals were flash-frozen and the two structures were determined and refined to 2. 1 A. Several new features were identified relative to the wild-type structure. Seven side-chains previously unplaced in the wild-type structure were identified and included in the model, and the amino acid terminus was extended by an alanine residue. Many additional water molecules were identified. Examination of the K230M active sites (K230M isocitrate and K230M-ketoglutarate) revealed that tyrosine 160 protrudes further into the active site in the presence of either isocitrate or alpha-ketoglutarate in K230 M than it does in the wild-type structure. Also, methionine 230 was not as fully extended, and asparagine 232 rotates approximately 30 degrees toward the ligand permitting polar interactions. Outside the active site cleft a tetragonal volume of density was identified as a sulfate molecule. Its location and interactions suggest it may influence the equilibrium between the tetragonal and the orthorhombic forms of isocitrate dehydrogenase. Differences observed in the active site water structure between the wild-type and K230M structures were due to a single point mutation. A water molecule was located in the position equivalent to that occupied by the wild-type epsilon-amine of lysine 230; a water molecule in that location in K230M suggests it may influence catalysis in the mutant. Comparison of K230M complexed with isocitrate and alpha-ketoglutarate illuminates the influence a ligand has on active site water structure.

Binding Sites↗
PubMed1975

[Inhibiton of isocitrate dehydrogenase and isocitrate lyase from Acinetobacter calcoaceticus by acids of the citrate and glyoxylate cycle].

Acinetobacter calcoaceticus contains two forms of NADP+-dependent isocitrate dehydrogenases differing, among others, by their molecular weights and regulatory properties. The regulation of the high-molecular form of isocitrate dehydrogenase and of isocitrate lyase by organic acids, either belonging or related to the citrate and glyoxalate cycle, is investigated. While alpha-ketoglutarate and oxalacetate competitively inhibit the isocitrate dehydrogenase against Ds-isocitrate, glyoxylate and pyruvate were found to increase Vmax and to lower the KM value for Ds-isocitrate and NADP+. Simultaneous addition of oxalacetate and glyoxylate (not, however, addition of the nonenzymatically formed condensation product of both compound) nullified the activation of isocitrate dehydrogenase by glyoxylate, and potentiates the inhibitory effect of oxalacetate. Alpha-ketoglutarate, succinate, and phosphoenolpyruvate inhibit the isocitrate lyase in a noncompetitive fashion against DS-isocitrate; L-malate, oxalacetate and glyoxylate inhibit competitively. The intermediates of the citrate and glyoxylate cycle afford additive inhibition of the isocitrate lyase. The importance of organic acids of the citrate and glyoxylate cycle and of phosphoenolpyruvate for the regulation of the citrate and glyoxylate cycle at the level of isocitrate dehydrogenase and isocitrate lyase is discussed.

Acinetobacter↗
PubMed1970

The role of nicotinamide-adenine dinucleotide phosphate-dependent malate dehydrogenase and isocitrate dehydrogenase in the supply of reduced nicotinamide-adenine dinucleotide phosphate for steroidogenesis in the superovulated rat ovary.

1. Superovulated rat ovary was found to contain high activities of NADP-malate dehydrogenase and NADP-isocitrate dehydrogenase. The activity of each enzyme was approximately four times that of glucose 6-phosphate dehydrogenase and equalled or exceeded the activities reported to be present in other mammalian tissues. Fractionation of a whole tissue homogenate of superovulated rat ovary indicated that both enzymes were exclusively cytoplasmic. The tissue was also found to contain pyruvate carboxylase (exclusively mitochondrial), NAD-malate dehydrogenase and aspartate aminotransferase (both mitochondrial and cytoplasmic) and ATP-citrate lyase (exclusively cytoplasmic). 2. The kinetic properties of glucose 6-phosphate dehydrogenase, NADP-malate dehydrogenase and NADP-isocitrate dehydrogenase were determined and compared with the whole-tissue concentrations of their substrates and NADPH; NADPH is a competitive inhibitor of all three enzymes. The concentrations of glucose 6-phosphate, malate and isocitrate in incubated tissue slices were raised at least tenfold by the addition of glucose to the incubation medium, from the values below to values above the respective K(m) values of the dehydrogenases. Glucose doubled the tissue concentration of NADPH. 3. Steroidogenesis from acetate is stimulated by glucose in slices of superovulated rat ovary incubated in vitro. It was found that this stimulatory effect of glucose can be mimicked by malate, isocitrate, lactate and pyruvate. 4. It is concluded that NADP-malate dehydrogenase or NADP-isocitrate dehydrogenase or both may play an important role in the formation of NADPH in the superovulated rat ovary. It is suggested that the stimulatory effect of glucose on steroidogenesis from acetate results from an increased rate of NADPH formation through one or both dehydrogenases, brought about by the increases in the concentrations of malate, isocitrate or both. Possible pathways involving the two enzymes are discussed.

Acetates↗
PubMed2006

Role of phosphoenolpyruvate in the NADP-isocitrate dehydrogenase and isocitrate lyase reaction in Escherichia coli.

Phosphoenolpyruvate inhibited Escherichia coli NADP-isocitrate dehydrogenase allosterically (Ki of 0.31 mM) and isocitrate lyase uncompetitively (Ki' of 0.893 mM). Phosphoenolpyruvate enhances the uncompetitive inhibition of isocitrate lyase by increasing isocitrate, which protects isocitrate dehydrogenase from the inhibition, and contributes to the control through the tricarboxylic acid cycle and glyoxylate shunt.

Escherichia coli↗
PubMed1987

Changes in the lipid composition and activities of isocitrate dehydrogenase and isocitrate lyase during encystation of Acanthamoeba culbertsoni strain A-1.

The contents of total lipids, total sterols, total and individual phospholipids: lysophosphatidyl choline, lysophosphatidyl ethanolamine, phosphatidyl choline, phosphatidyl ethanolamine and alkali-stable phospholipids I and II, were significantly lower in mature cysts of Acanthamoeba culbertsoni strain A-1 than in trophozoites. The major constituent sterols of trophozoites, viz. ergosterol, 7-dehydrostigmasterol and 7,22,25-tridehydrostigmasterol which resolved as a single spot on thin-layer chromatography, disappeared in the cysts. When trophozoites grown in the presence of [14C]acetate were transferred to encystation medium, there was a steady decrease in the radioactivity in the lipids and acid-soluble fraction (glycogen) of the encysting cells while the radioactivity increased in the akali-insoluble fraction (cellulose). The activity of isocitrate lyase in the encysting cells steadily increased up to 24 h of encystation, followed by a slight decrease during 24-32 h, but the activity of isocitrate dehydrogenase steadily decreased up to 32 h of encystation, beyond which time no enzyme activity was detected. Inhibitors of isocitrate lyase, glycolate and maleate at 8.5 to 34 mM concentration inhibited encystation by 18-67%.

Acanthamoeba↗