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

---

Query: EC:1.1.1.41 (isocitrate dehydrogenase)
3,101 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Electron paramagnetic resonance (EPR) spectra were obtained for various isocitrate dehydrogenase-Mn(II) complexes. The qualitative effects of the binding of substrates, nucleotides, and substrate analogues on the isotropic character of the electronic environment of enzyme-bound Mn(II) were subsequently investigated. The addition of isocitrate produces a markedly anisotropic spectrum whereas alpha-ketoglutarate does not alter the spectrum of enzyme-Mn(II) substantially. This suggests direct coordination of isocitrate to the Mn(II) but perphaps a different mode of binding for alpha-ketoglutarate. Other studies demonstrated mutually exclusive binding relationships between TPN and TPNH, between Mn-isocitrate and TPNH, and between HCO3-(CO2) and formate or thiocyanate. Indirect evidence supporting CO2 rather than HCO3-as the actual reactive species which binds to the enzyme in the reductive carboxylation reaction is presented on the basis of the results of the formate and thiocyanate studies. From the EPR results recorded for ternary, quaternary, and quinary enzyme-substrate complexes, correlations between the appearance of fine structure signals and the binding of individual substrates and/or nucleotides are found, and tentative assignments of such signals are made on this basis. Additional studies were conducted to determine binding constants for Mg(II) Co(II), and Co-isocitrate, and a comparison was made with kinetically determined binding constants.
...
PMID:Structure-function relationships in TPN-dependent isocitrate dehydrogenase. I. Electron paramagnetic resonance studies of the interaction of enzyme-bound Mn(II) with substrates, cofactors, and substrate analogues. 1 44

The metabolism of pyruvate by the adult filarial parasites Brugia pahangi, Dipetalonema viteae, and Litomosoides carinii has been compared. Istopic carbon-balance studies indicate the presence of significant pyruvate dehydrogenase activity in L. carinii but little or no activity in either B. pahangi or D. viteae. In all 3 helminths, the quantities of pyruvate that were completely oxidized to CO2 and water were very small. The activities of some of the tricarboxylic acid cycle enzymes of B. pahangi also were determined. In particular, a relatively low level of isocitrate dehydrogenase was noted in the mitochondria of B. pahangi. It is suggested that the tricarboxylic acid energy generating pathway is of doubtful importance as an energy yielding pathway in any of these parasites.
...
PMID:Comparative utilization of pyruvate by Brugia pahangi, Dipetalonema viteae, and Litomosoides carinii. 57 9

Tricarboyxlic acid cycle activity was examined in Neisseria gonorrhoeae CS-7. The catabolism of glucose in N. gonorrheae by a combination of the Entner-Doudoroff and pentose phosphate pathways resulted in the accumulation of acetate, which was not further catabolized until the glucose was depleted or growth became limiting. Radiorespirometric studies revealed that the label in the 1 position of acetate was converted to CO2 at twice the rate of the label in the 2 position, indicating the presence of a tricarboxylic acid cycle. Growth on glucose markedly reduced the levels of all tricarboxylic acid cycle enzymes except citrate synthase (EC 4.1.3.7). Extracts of glucose-grown cells contained detectable levels of all tricarboxylic acid cycle enzymes except aconitase (EC 4.2.1.3), isocitrate dehydrogenase (EC 1.1.1.42), and a pyridine nucleotide-dependent malate dehydrogenase (EC 1.1.1.37). Extracts of cells capable of oxidizing acetate lacked only the pyridine nucleotide-dependent malate dehydrogenase. In lieu of this enzyem, a particulate pyridine nucleotide-independent malate oxidase (EC 1.1.3.3) was present. This enzyme required flavin adenine dinucleotide for activity and appeared to be associated with the electron transport chain. Radiorespirometric studies utilizing labeled glutamate demonstrated that a portion of the tricarboxylic acid cycle functioned during glucose catabolism. In spite of the presence of all tricarboxylic acid cycle enzymes, N. gonorrhoeae CS-7 was unable to grow in medium supplemented with cycle intermediates.
...
PMID:Physiology and metabolism of pathogenic neisseria: tricarboxylic acid cycle activity in Neisseria gonorrhoeae. 82 68

The occurrence and levels of activity of various enzymes of carbohydrate catabolism in culture forms (promastigotes) of 4 human species of Leishmania (L. brasiliensis, L. donovani, L. mexicana, and L. tropica) were compared. These organisms possess enzymes of the Embden-Meyerhof pathway but lack lactate dehydrogenase. No evidence could be found for the production of lactic acid by growing cultures and lactic acid could not be detected either in cell-free preparations or after incubation of cell-free extracts with pyruvate and NADH under appropriate conditions. All 4 species possess alpha-glycerophosphate dehydrogenase and alpha-glycerophosphate phosphatase which together could regenerate NAD, thus compensating for the absence of lactate dehydrogenase. The oxidative and nonoxidative reactions of the hexose monophosphate pathway are present in all 4 species. Cell-free extracts have pyruvate dehydrogenase activity which allows the entry of pyruvate into and its subsequent oxidation through the tricarboxylic acid cycle. All enzymes of this cycle, including a thiamine pyrophosphate dependent alpha-ketoglutarate dehydrogenase, are present. Both NAD and NADP-linked malate dehydrogenase activities are present. The isocitrate dehydrogenase is NADP specific. There is an active glutamate dehydrogenase which could compete with alpha-ketoglutarate dehydrogenase for the common substrate (alpha-ketoglutarate). Replenishment of C4 acids is accomplished by heterotrophic CO2 fixation catalyzed by pyruvate carboxylase. All 4 species have high levels of NADH oxidase activity. Several enzymes thus far not found in any species of Leishmania have been demonstrated. These are: phosphoglucose isomerase, triose phosphate isomerase, fructose-1, 6-diphosphatase, 3-phosphoglycerate kinase, enolase, alpha-glycerophosphate dehydrogenase, alpha-glycerophosphate phosphatase, pyruvate dehydrogenase complex, citrate synthase, aconitase, alpha-ketoglutarate dehydrogenase, glutamate dehydrogenase, and NADH oxidase.
...
PMID:Enzymes of carbohydrate metabolism in four human species of Leishmania: a comparative survey. 100 46

Carbon-14 was incorporated into oxalate and CO2 from either citrate-1,5-14C, succinate-1,4-14C, or fumarate-1,4-14C by cultures of Aspergillus niger pregrown on a medium which contained glucose as the sole carbon source and which did not allow citrate accumulation. In cell-free extracts of mycelium forming oxalate and CO2 from added citrate the following enzymes of the tricarboxylic acid (TCA) cycle were identified: citrate synthase CE 4.1.3.7), aconitate hydratase (EC4.2.1.3), NAD and NADP-dependent isocitrate dehydrogenase (EC 1.1.1.41, 1.1.1.42), (alpha-oxoglutarate dehydrogenase (EC 1.2.4.2), succinate dehydrogenase (EC 1.3.99.1), fumarate hydratase (EC 4.2.1.2), and malate dehydrogenase (EC 1.1.1.37). The in vitro activity of aconitate hydratase and of NADP-dependent isocitrate dehydrogenase was shown to be almost identical to the rate of in vivo degradation of citrate or to exceed this rate. The degradation of citrate to oxalate was inhibited completely by 9 mM fluoroacetate. It is concluded that the TCA cycle is involved in the formation of oxalate from citrate.
...
PMID:Oxalate accumulation from citrate by Aspergillus niger. II. Involvement of the tricarboxylic acid cyclase. 115

O2-induced impairment of mitochondrial energy generation was examined in intact lungs isolated from rats after 18-30 h exposure to either air or 100% O2 in vivo. Mitochondrial metabolic rates were determined by separate measurements of 14CO2 production from [1-14C]pyruvate and [U-14C]palmitate, perfused under normal and stimulated metabolic conditions brought about by perfusion with the uncoupler of oxidative phosphorylation, 2,4-dinitrophenol (DNP). In the absence of DNP, O2 exposure did not significantly alter 14CO2 productions from either substrate. DNP increased lung pyruvate and palmitate catabolism to CO2 twofold in air-exposed lungs but did not alter 14CO2 production in lungs isolated from O2-exposed rats. These data demonstrated an O2-induced impairment of maximal mitochondrial metabolism of both pyruvate and palmitate that could not be explained by alterations in tissue free coenzyme A or by loss of pyridine nucleotides. However, comparisons of the steady-state levels of tricarboxylic acid cycle intermediates between O2- and air-exposed lungs did identify isocitrate dehydrogenase as a possible site of O2-induced enzyme inactivation.
...
PMID:Tricarboxylic acid cycle activity in perfused rat lungs after O2 exposure. 131 4

The cytoplasmic malic enzyme (Mod-1) catalyzes the oxidative decarboxylation of malate: malate + NADP+----pyruvate + CO2 + NADPH + H+. Using a cDNA clone of Mod-1 as a probe, two new DNA markers not at the Mod-1 locus (restriction fragment length polymorphisms, RFLP) were detected by Southern blot analysis that showed extensive homology to Mod-1 sequences. Linkage of each restriction fragment length polymorphism to loci other than Mod-1 was assessed using the BXD (C57BL/6J x DBA/2J) recombinant inbred strains and confirmed by backcrosses. One polymorphic site, designated D9Rti1, was found to be closely linked to the phosphoglucomutase (Pgm-3) locus on Chromosome 9. The other hybridization site, designated D1Rti2, was closely linked to the isocitrate dehydrogenase (Idh-1) locus on Chromosome 1. The data presented imply that Mod-1 homologous sequences are tightly linked to three different metabolic enzymes.
...
PMID:A malic enzyme probe detects cross-hybridizing sequences closely linked to loci encoding other metabolic enzymes. 134 82

A rapid switch from a fermentative to a primarily oxidative type of glucose utilization was observed during in vitro differentiation of Trypanosoma brucei STIB348 and EATRO1244 bloodstream to procyclic trypomastigotes. In accordance with previously published reports bloodstream populations produced pyruvate as the major end product of glucose catabolism, together with very small amounts of CO2, succinate and glycerol. During differentiation pyruvate excretion decreased within 48 h to the low levels produced by 28-day procyclic stages. Concomitant with the decline in pyruvate formation, acetate appeared as a new product and the rates of respiratory CO2 increased considerably. The amount of carbon released with these compounds could account for nearly all of the glucose carbon consumed. Rates of glucose utilization and formation of acetate and CO2 in cells differentiated for 48 h were essentially the same as those found in 28-day procyclics. Succinate and glycerol excretion remained low during the entire transformation process, and no significant difference in the pattern and quantities of end products were found between the two trypanosome strains. During trypanosome differentiation the changes in metabolism were associated with marked alterations in enzyme activity levels. Activities of the tricarboxylic acid (TCA) cycle enzymes citrate synthase, isocitrate dehydrogenase (NAD+), succinate dehydrogenase and fumarase were not detectable in bloodstream trypomastigotes but appeared upon differentiation for 24 h. An exception was citrate synthase whose activity was not demonstrable until 48 h postinoculation into culture. After 48 h the majority of the TCA cycle enzyme activities continued to increase steadily until day 28. Pyruvate kinase activity decreased in differentiating cells after 48 h to about 25% of the level found in bloodstream trypomastigotes.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Alterations in Krebs cycle enzyme activities and carbohydrate catabolism in two strains of Trypanosoma brucei during in vitro differentiation of their bloodstream to procyclic stages. 190 88

The in vitro metabolism of [1-13C]glucose by Ascaris suum third and fourth-stage larvae was analyzed under different gas phases using 13C nuclear magnetic resonance spectroscopy (13C-NMR). Third-stage larvae (L3) incubated under a gas phase of 85% N2/5% O2/10% CO2 produced trace amounts of [13C]succinate, and molted to fourth-stage larvae (L4) between days 3 and 4 in vitro. However, they appeared to arrest as L3s when incubated under air, or 85% N2/5% O2/10% CO2 in the presence of 2 mM potassium cyanide, or 95% N2/5% CO2. Day 12 L4 (eight days after molting) incubated under 85% N2/5% O2/10% CO2, or 95% N2/5% CO2, or 94% N2/1% O2/5% CO2, produced succinate, acetate, propionate and the branched-chain fatty acids 2-methylvalerate and 2-methylbutyrate by fermentative pathways characteristic of adult body wall muscle. In contrast, when Day 12 L4 were incubated under air, only trace amounts of these acids were detected in the incubation medium. Thus, L4 are capable of synthesizing end-products typical of the adult even in the presence of oxygen, as long as the CO2 tensions are above 5%. As would be predicted, activities of enzymes involved in aerobic metabolism, including citrate synthase, isocitrate dehydrogenase, and cytochrome oxidase, decreased dramatically as L4s underwent the final ecdysis and matured to the adult stage. More importantly, activities of enzymes typical of anaerobic metabolism, including phosphoenolpyruvate carboxykinase and malic enzyme, were substantially elevated in L3s (over their levels in second-stage larvae), and appeared to have reached their adult levels in L3s prior to the third molt, even though L3s still exhibited cyanide sensitivity. Since L3s and L4s have enzymes involved in both aerobic and anaerobic pathways, it is possible that the L3s contain two populations of mitochondria, one which functions aerobically and a second which functions anaerobically.
...
PMID:Effect of gas phase on carbohydrate metabolism in Ascaris suum larvae. 250 8

In Escherichia coli, isocitrate dehydrogenase (IDH) is regulated by phosphorylation. This phosphorylation cycle is catalyzed by an unusual, bifunctional protein:IDH kinase/phosphatase. IDH kinase/phosphatase is expressed from a single gene, aceK, and both activities are catalyzed by the same polypeptide. The amino acid sequence of IDH kinase/phosphatase does not exhibit the characteristics which are typical of other protein kinases, although it does contain a consensus ATP binding site. The available evidence suggests that the IDH kinase and IDH phosphatase reactions occur at the same active site and that the IDH phosphatase reaction results from the back reaction of IDH kinase tightly coupled to ATP hydrolysis. The function of the IDH phosphorylation cycle is to control the flux of isocitrate through the glyoxylate bypass. This pathway is essential for growth on acetate because it prevents the quantitative loss of the acetate carbons as CO2 in the Krebs' cycle. IDH kinase/phosphatase monitors general metabolism by responding to the levels of a wide variety of metabolites, many of which activate IDH phosphatase and inhibit IDH kinase. The ability of IDH kinase/phosphatase to monitor general metabolism allows. the IDH phosphorylation cycle to compensate for substantial perturbations of the system, such as a 15-fold overproduction of IDH. The significance of the cellular level of IDH kinase/phosphatase has also been evaluated. The level of this protein is in great excess of that required for steady-state growth on acetate. In contrast, IDH kinase/phosphatase is, in some cases, rate-limiting for the dephosphorylation of IDH which results when preferred carbon sources are added to cultures growing on acetate.
...
PMID:Isocitrate dehydrogenase kinase/phosphatase. 255 93


1 2 3 4 5 Next >>

---