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)

The investigation of Krebs cycle state in kidney homogenates of August rats subjected to oral intoxication with oil solution of yellow phosphorus in a dose of 0.3 mg/kg, has shown that under conditions of balanced nutrition the activity of NAD-dependent isocitrate dehydrogenase, succinate dehydrogenase and accumulation of the substrate fund of the cycle decreased 3.5-fold as compared to the control. The addition of polyunsaturated fatty acids to the ration produced a positive effect on Krebs cycle state: dehydrogenase activity was not significantly changed, accumulation of Krebs cycle substrate was two-fold lower. However, this ration did not completely abolish the toxic action of yellow phosphorus on Krebs cycle.
...
PMID:[Effects of polyunsaturated fatty acids on Krebs cycle in the rat kidney in chronic phosphorus intoxication]. 151 57

D-Glucose causes a preferential stimulation of mitochondrial oxidative events relative to glycolysis in pancreatic islets. The possible participation of a Ca(2+)-induced activation of NAD-isocitrate dehydrogenase in this process was investigated. The activity of the enzyme in rat islet homogenates was measured through the generation of either NADH or 2-ketoglutarate. In the absence of Ca2+ and ADP, half-maximal velocities were recorded at isocitrate and NAD+ concentrations close to 1.2 and 0.5 mM, respectively. At isocitrate concentrations in the 0.15-1.5 mM range, ADP (1.0 mM) markedly increased the reaction velocity recorded in the absence of Ca2+ and conferred to the enzyme the property of being activated by Ca2+, with a Ka for Ca2+ somewhat below 1.0 microM. From these data and by comparison with the activity of 2-ketoglutarate dehydrogenase, it is proposed that activation of NAD-isocitrate dehydrogenase by such factors as ADP and Ca2+ may be required in order to match, in nutrient-stimulated islets, the rates of 2-ketoglutarate generation and oxidative decarboxylation.
...
PMID:Hexose metabolism in pancreatic islets. Regulation of NAD-isocitrate dehydrogenase activity. 152 69

NAD(+)-dependent isocitrate dehydrogenase from Saccharomyces cerevisiae is composed of two nonidentical subunits, designated IDH1 and IDH2. The gene encoding IDH2 was previously cloned and sequenced (Cupp, J.R., and McAlister-Henn, L. (1991) J. Biol. Chem. 266, 22199-22205), and in this paper we describe the isolation of a yeast genomic clone containing the IDH1 gene. A fragment of the IDH1 gene was amplified by the polymerase chain reaction method utilizing degenerate oligonucleotides based on tryptic peptide sequences of the purified subunit; this fragment was used to isolate a full length IDH1 clone. The nucleotide sequence of the IDH1 coding region was determined and encodes a 360-residue polypeptide including an 11-residue mitochondrial targeting presequence. Amino acid sequence comparison between IDH1 and IDH2 reveals a 42% sequence identity, and both IDH1 and IDH2 show approximately 32% identity to Escherichia coli NAD(P)(+)-dependent isocitrate dehydrogenase. To examine the function of the IDH1 subunit and to determine the metabolic role of NAD(+)-dependent isocitrate dehydrogenase the IDH1 gene was disrupted in a wild type haploid yeast strain and in a haploid strain lacking IDH2. The IDH1 disruption strains expressed no detectable IDH1 as determined by Western blot analysis, and these strains were found to lack NAD(+)-dependent isocitrate dehydrogenase activity indicating that IDH1 is essential for a functional enzyme. Over-expression of IDH1 in a strain containing IDH2 restored wild type activity but did not result in increased levels of activity, suggesting that both IDH1 and IDH2 are required for a functional enzyme. Growth phenotype analysis of the IDH1 disruption strains revealed that they grew at a reduced rate on the nonfermentable carbon sources examined (glycerol, lactate, and acetate), consistent with NAD(+)-dependent isocitrate dehydrogenase performing a critical role in oxidative function of the citric acid cycle. In addition, the IDH1 disruption strains grew at wild type rates in the absence of glutamate, indicating that these strains are not glutamate auxotrophs.
...
PMID:Cloning and characterization of the gene encoding the IDH1 subunit of NAD(+)-dependent isocitrate dehydrogenase from Saccharomyces cerevisiae. 164 26

In rat kidney several mitochondrial and soluble enzyme activities are stimulated by thyroid hormones and the mitochondrial membrane fluidity is also increased. However, the ketone metabolism enzyme activities of D-3-hydroxybutyrate dehydrogenase and of 3-oxoacid CoA-transferase are not significantly affected by the hyperthyroid state and the ketone body concentration is not greatly changed. Therefore, in hyperthyroid rats the response of the kidney, as far as the ketone bodies and their metabolizing enzymes are concerned, is at variance with that of the liver and the heart. In the brain of young rats, age 8-9 weeks, the activities of the enzymes of ketone body metabolism and those responsible for other metabolic pathways are not influenced by the hyperthyroid state. In these animals, however, the activities of two enzymes, NAD-isocitrate dehydrogenase and pyruvate kinase, are still stimulated by 28 and 41%, respectively. This can be probably related to the higher energy requirement for definitive brain maturation in young hyperthyroid rats.
...
PMID:Differential action of thyroid hormones on the activity of certain enzymes in rat kidney and brain. 178 8

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

An isocitrate dehydrogenase able to function with either NADP or NAD as coenzyme was purified to homogeneity from cell-free extracts of the purple photosynthetic eubacterium Rhodomicrobium vannielii using a rapid two-step procedure involving dye-ligand affinity chromatography. The enzyme was obtained in 60% yield with specific activities of 23 U.mg protein-1 (NADP-linked reaction) and 18.5 U.mg protein-1 (NAD-linked reaction). The purified enzyme was monomeric and migrated with an approximate Mr of 75,000-80,000 on both SDS/PAGE and non-denaturing PAGE. Affinity constants (Km values) of 2.5 microM for NADP and 0.77 mM for NAD and values for kcat/Km of 981,200 min-1.mM-1 (NADP) and 2455 min-1.mM-1 (NAD) indicated a greater specificity for NADP compared to NAD. A number of metabolites were examined for possible differential regulatory effects on the NADP- and NAD-linked reactions, using a dual-wavelength assay. Oxaloacetate was found to be an effective inhibitor of both reactions and the enzyme was also sensitive to concerted inhibition by glyoxylate and oxaloacetate. The amino-acid composition and the identity of 39 residues at the N-terminus were determined and compared to other isocitrate dehydrogenases. The results suggested a relationship between the Rm. vannielii enzyme and the monomeric isocitrate dehydrogenase isoenzyme II from Vibrio ABE-1.
...
PMID:Purification and characterization of a monomeric isocitrate dehydrogenase with dual coenzyme specificity from the photosynthetic bacterium Rhodomicrobium vannielii. 193 83

NAD(+)-dependent isocitrate dehydrogenase from Saccharomyces cerevisiae is composed of two nonidentical subunits, designated IDH1 (Mr approximately 40,000) and IDH2 (Mr approximately 39,000). We have isolated and characterized a yeast genomic clone containing the IDH2 gene. The amino acid sequence deduced from the gene indicates that IDH2 is synthesized as a precursor of 369 amino acids (Mr 39,694) and is processed upon mitochondrial import to yield a mature protein of 354 amino acids (Mr 37,755). Amino acid sequence comparison between S. cerevisiae IDH2 and S. cerevisiae NADP(+)-dependent isocitrate dehydrogenase shows no significant sequence identity, whereas comparison of IDH2 and Escherichia coli NADP(+)-dependent isocitrate dehydrogenase reveals a 33% sequence identity. To confirm the identity of the IDH2 gene and examine the relationship between IDH1 and IDH2, the IDH2 gene was disrupted by genomic replacement in a haploid yeast strain. The disruption strain expressed no detectable IDH2, as determined by Western blot analysis, and was found to lack NAD(+)-dependent isocitrate dehydrogenase activity, indicating that IDH2 is essential for a functional enzyme. Overexpression of IDH2, however, did not result in increased NAD(+)-dependent isocitrate dehydrogenase activity, suggesting that both IDH1 and IDH2 subunits are required for catalytic activity. The disruption strain was unable to utilize acetate as a carbon source and exhibited a 2-fold slower growth rate than wild type strains on glycerol or lactate. This growth phenotype is consistent with NAD(+)-dependent isocitrate dehydrogenase performing an essential role in the oxidative function of the citric acid cycle.
...
PMID:NAD(+)-dependent isocitrate dehydrogenase. Cloning, nucleotide sequence, and disruption of the IDH2 gene from Saccharomyces cerevisiae. 193 42

In several metabolic encephalopathies, hyperammonemia and organic acidemia are consistently found. Ammonia and fatty acids (FAs) are neurotoxic: previous workers have shown that ammonia and FAs can act singly, in combination, or synergistically, in inducing coma in experimental animals. However, the biochemical mechanisms underlying the neurotoxicity of ammonia and FAs have not been fully elucidated. FAs are normally converted to their corresponding CoA derivatives (CoAs) once they enter cells and it is known that these fatty acyl CoAs can alter intermediary metabolism. The present study was initiated to determine the effects of ammonia and fatty acyl CoAs on brain mitochondrial dehydrogenases. At a pathophysiological level (2 mM), ammonia is a potent inhibitor of brain mitochondrial alpha-ketoglutarate dehydrogenase complex (KGDHC). Only at toxicological levels (10-20 mM) does ammonia inhibit brain mitochondrial NAD(+)- and NADP(+)- linked isocitrate dehydrogenase (NAD-ICDH, NADP-ICDH), and NAD(+)-linked malate dehydrogenase (MDH) and liver mitochondrial NAD-ICDH. Butyryl- (BCoA), octanoyl- (OCoA), and palmitoyl (PCoA) CoA were potent inhibitors of brain mitochondrial KGDHC, with IC50 values of 11, 20, and 25 microM, respectively; moreover, the inhibitory effect of fatty acyl CoAs and ammonia were additive. At levels of 250 microM or higher, both OCoA (IC50 = 1.15 mM) and PCoA (IC50 = 470 microM) inhibit brain mitochondrial NADP-ICDH; only at higher levels (0.5-1 mM) does BCoA inhibit this enzyme (by 30-45%). Much less sensitive than KGDHC and NADP-ICDH, brain mitochondrial NAD-ICDH is only inhibited by 1 mM BCoA, OCoA, and PCoA by 22%, 35%, and 44%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Neurotoxicity of ammonia and fatty acids: differential inhibition of mitochondrial dehydrogenases by ammonia and fatty acyl coenzyme A derivatives. 194 69

Lidocaine or aminazine (chlorpromazine) injected to rats or incubated with liver mitochondria prevented NAD-isocitrate dehydrogenase and transhydrogenase activation during the subsequent incubation of mitochondria with cAMP. Integrity of mitochondrial membranes is obligatory for manifestation of the drugs effect. Lidocaine and aminazine-induced desensitization of mitochondria to the cAMP action was apparently realized via alteration in the state (and/or composition) of lipid component of mitochondria. The significance of mitochondria sensitivity to cAMP stimulation is discussed.
...
PMID:[Prevention of cAMP stimulation of activity of various oxidative mitochondrial enzymes with lidocaine and aminazine]. 196 20

Mitochondrial NADP(H)-specific isocitrate dehydrogenase (IDP1) was purified from yeast cells grown with acetate as a carbon source. IDP1 was shown to be a dimer with a subunit molecular weight of approximately 45,000. Immunochemical levels of IDP1 were found to vary in inverse proportion with those of mitochondrial NAD(H)-specific isocitrate dehydrogenase in cells grown with glucose or with acetate as a carbon source. A 20-residue amino-terminal sequence was obtained for IDP1, and degenerate oligonucleotides were used to synthesize a 50-base pair polymerase chain reaction product corresponding to the coding region for a portion of the amino terminus. The 50-base pair DNA fragment was used as a hybridization probe to identify plasmids containing the IDP1 gene in a yeast genomic DNA library. The complete nucleotide sequence of the IDP1 coding region was determined and translated into a 412-residue amino acid sequence for the mature protein which is preceded by a putative 16-residue mitochondrial targeting presequence. A haploid yeast strain containing a chromosomal disruption of the IDP1 locus was constructed and found to be capable of growth with glucose but not with other carbon sources, suggesting that IDP1 provides a critical function and may be the primary source of NADPH in yeast mitochondria.
...
PMID:Isolation, nucleotide sequence, and disruption of the Saccharomyces cerevisiae gene encoding mitochondrial NADP(H)-specific isocitrate dehydrogenase. 198 87


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---