Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.1.1.41 (isocitrate dehydrogenase)
 3,101 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 17 beta-hydroxysteroid dehydrogenase which was purified from porcine testicular microsomal fraction [Inano, H. and Tamaoki, B (1974) Eur. J. Biochem. 44, 13-23] catalyzed the reduction of androstenedione to testosterone with the accompanying oxidation of equimolar NADPH. For the oxido-reduction of the steroids, the 17 beta-hydroxysteroid dehydrogenase preferred NADP(H) to NAD(h). Transhydrogenation from NADPH to NAD+ or NADH to NADP+ through the cyclic oxido-reduction of the steroids by the purified 17 beta hydroxysteroid dehydrogenase preparation was not spectrophotometrically detectable, because of selective preference of the testicular 17 beta-hydroxysteroid dehydrogenase against NADP(H). To examine stereospecific transfer of the hydrogen from NADPH to androstenedione by the purified 17 beta-hydroxysteroid dehydrogenase, the following tritiated cofactors were synthesized: [4-3-H]NADP+ was prepared by catalytic replacement from non-radioactive NADP+ and 3H2O in the presence of potassium cyanide. Then, [4-pro-R3H]NADPH was enzymatically synthesized from the [4-3H]NADP+ by glucose 6-phosphate and its dehydrogenase. On the other hand, [4-pro-S-3H]NADPH was prepared from the [4-3H]NADP+ by isocitrate and isocitrate dehydrogenase. When androstenedione was incubated with the 17 beta-hydroxysteroid dehydrogenase in the presence of these stereospecifically 3H-labeled cofactors, only the tritium located at 4-pro-S position of the nicotinamide moiety of NADPH was transferred to testosterone. The location of the tritium in the testosterone molecule produced, 17alpha-position of the steroid, was assigned by the fact that the tritium of the testosterone remained in its molecule after acetylation, but was completely lost by oxidation.
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PMID:Relationship between steroids and pyridine nucleotides in the oxido-reduction catalyzed by the 17 beta-hydroxysteroid dehydrogenase purified from the porcine testicular microsomal fraction. 23 55

The segmentation of the proximal tubules in the kidney of the female rat was studied by means of enzyme histochemical reactions and the results compared with those observed in male and recently described by Jacobsen and J0rgensen (1973 a). Reactions were performed for the following soluble, coezyme-dependent oxido-reductases: glucose 6-phosphate dehydrogenase, alpha-glycerophosphate dehydrogenase, 3 alpha-hydroxysteroid dehydrogenase, NAD-as well as NADP-dependent isocitrate dehydrogenases, NAD-dependent malate dehydrogenase, NADP-dependent, decarboxylating malate dehydrogenase, uridine diphosphate glucose dehydrogenase. Measures were taken to reduce enzyme diffusion and eliminate interference from tissue tetrazolium reductases. Furthermore, reactions were performed for a number of less soluble or insoluble enzymes: glucose 6-phosphatase, mitochondrial alpha-glycerophosphate dehydrogenase, beta-hydroxybutyrate dehydrogenase, succinate dehydrogenase and tetrazolium reductases. In the proximal tubules of the female rat all enzymes studied--except beta-hydroxybutyrate dehydrogenase--showed segmental differences, most of them clearly revealing three segments. Sex differences were found concerning all enzymes except uridine diphosphate glucose dehydrogenase and NADP-dependent isocitrate dehydrogenase. The most pronounced sex-related differences were seen in the third segment in which part the male rat showed highest activity in respect to tetrazolium reductases, NAD-dependent isocitrate dehydrogenase, succinate dehydrogenase, beta-hydroxybutyrate dehydrogenase, 3 alpha-hydroxysteroid dehydrogenase and glucose 6-phosphate dehydrogenase and the female in respect to glucose 6-phosphatase, alpha-glycerophosphate dehydrogenases, and NADP-dependent, decarboxylating malate dehydrogenase. A few of the enzymes exhibited minor sex differences in the first two segments.
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PMID:Enzyme histochemical observations on the segmentation of the proximal tubules in the kidney of the female rat. 23 55

Controls of fatty acid synthesis in bovine adipose tissue were investigated. Six Brown Swiss steers were fasted for 8 days and then refed for 56 days. Biopsy samples of backfat adipose tissue were taken during the fasting and refeeding periods. Rates of acetate incorporation into fatty acids (FAS), activities of acetyl CoA carboxylase (CBX), glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and NADP:isocitrate dehydrogenase, and plasma free fatty acids (FFA) and plasma acetate were determined. FAS decreased 60% after 1 day of fasting and 99% after 8 days. FAS did not increase until day 3 of refeeding when energy intake was above maintenance, then returned to normal by 14 days. CBX followed a pattern similar to FAS, except its activity did rise above the control rate during refeeding. Plasma FFA increased 350% and acetate decreased 67% during fasting. After 4 days of refeeding, FFA returned to normal, and acetate increased to 156% of initial concentration, then returned to normal by 21 days. These data suggest that CBX limits FAS in adipose tissue of cattle.
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PMID:Changes in fatty acid synthesis and lipogenic enzymes in adipose tissue from fasted and fasted-refed steers. 23 91

D-Garcinia acid (D-threo-1,2-dihydroxy-1,2,3-propanetricarboxylate), like D-isocitrate, has an alpha-DS-hydroxyl group and a beta-LS configuration of the second carboxyl group. The maximal velocity of pyridine nucleotide reduction with D-garcinia acid is 8 and 21% of D-threo-isocitrate with the DPN-linked and TPN-linked isocitrate dehydrogenase from bovine heart, respectively. The other stereoisomers of hydroxycitrate [L-garcinia acid, D- and L-hibiscus acid (D- and L-erythro-1,2-dihydroxy-1,2,3-propanetricarboxylate)] are inactive. DL-threo-Homoisocitrate (DL-threo-1-hydroxy-1,2,4-butanetricarboxylate) supports DPN+ reduction at 10-15% of the rate observed for isocitrate with the DPN-specific enzyme, but is not a substrate for TPN-linked isocitrate dehydrogenase. The values of apparent S0.5 for total isocitrate and total garcinia acid are similar with both enzymes; the apparent S0.5 of total homoisocitrate is two- to threefold higher than that of total isocitrate with the DPN-linked enzyme. Enzymatic oxidative decarboxylation of garcinia acid and homoisocitrate leads to formation of alpha-keto-beta-hydroxyglutarate and alpha-ketoadipate, respectively. DL-Methylmalate (DL-1-hydroxy-2-methylsuccinate) is inactive as a substrate for either dehydrogenase as are the newly synthesized compounds: DL-threo-gamma-isocitrate amide (DL-threo-1-hydroxy-3-carbamy01,2-propanedicarboxylate), beta-methyl-DL-isocitrate (DL-1-hydroxy-2-methyl-1,2,3-propanetricarboxylate), beta-methyl-DL-garcinia acid (DL-threo-1-hydroxyl-2-methoxy-1,2,3-propanetricarboxylate), DL-1-hydroxyl-1,2,2-ethanetricarboxylate, and DL-1,4-dihydroxy-1,2-butanedicarboxylate.
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PMID:Substrate activity of structural analogs of isocitrate for isocitrate dehydrogenases from bovine heart. 23 63

Serum gamma glutamyl transpeptidase (GGTP), isocitrate dehydrogenase (ICD), ornithine carbamoyl transferase (OCT), alanine aminotransferase (AlT), aspartate aminotransferase (AsT), and alkaline phosphatase (ALP) activities were assayed in 67 alcoholics and 40 drug dependent patients. Bilirubin, total protein, albumin, and globulin were also measured. GGTP elevation was observed in 48% of alcoholics and in 50% of drug dependents. The incidences of elevated levels of other enzymes were: ICD 39 and 38-7%; OCT 23-7 and 36-1%; AlT 30 and 33%; AsT 24-2 and 21-7%; ALP 10-4 and 5% respectively. Measurement of GGTP is thus more useful as a screening test for involvement of the liver in alcoholics and drug dependent patients than that of the other enzymes.
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PMID:Serum enzyme levels in alcoholism and drug dependency. 23 23

Alpha-Methylisocitrate (3-hydroxy-1,2,3-butanetricarboxylate) is a potent inhibitor, competitive with isocitrate (1-hydroxy-1,2,3-propanetricarboxylate), of the TPN-linked isocitrate dehydrogenase from bovine heart and rat liver; it does not inhibit the DPN-specific enzyme from these tissues. In the presence of magnesium ion, values of Kis for DL-alpha-methylisocitrate for purified bovine heart enzyme, rat liver cytosol, and rat liver mitochondrial extract were in the range of 0.1 muM to 0.3 muM. This compared to values of apparent Km for DL-isocitrate for the same tissue preparations of 14 muM to 20 muM. One of the DL isomer pairs of alpha-methylisocitrate was inactive; the observations suggest that it is threo-alpha-methylisocitrate which inhibits TPN-linked isocitrate dehydrogenase. A method of synthesis of DL-threo-alpha-methylisocitric lactone (2-methyl-5-oxo-2,3-furandicarboxylic acid) from dimethyl trans-epoxymethylsuccinate and dimethylmalonate is described.
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PMID:Alpha-methylisocitrate. A selective inhibitor of TPN-linked isocitrate dehydrogenase from bovine heart and rat liver. 23 45

The nicotinamide adenine dinucleotide phosphate (NADP)-specific isocitrate dehydrogenase from Blastocladiella emersonii was purified. The enzyme was very unstable. Satisfactory stability was obtained in the presence of 0.2% ovalbumin. The enzyme had a molecular weight of about 100,000. It did not exhibit homotropic cooperativity for any of it substrates and was not affected by the allosteric modifiers citrate and adenosine monophosphate, diphosphate, and tri-phosphate. The substrate saturation studies showed both intercept and slope effects in Lineweaver-Burk plots. The Km values for isocitrate and NADP were found to be 20 and 10 muM, respectively. The product inhibition pattern was compatible with a random sequential reaction mechanism. The enzyme catalyzed the oxidative decarboxylation of isocitrate about six times better than the reductive carboxylation of alpha-ketoglutarate. The enzyme was inhibited by glyoxylate plus oxalacetate. Assays conducted in the presence of low Mg2+ concentrations exhibited a lag. This lag could be abolished by the addition of reduced NADP to the assay mixture.
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PMID:Properties of the nicotinamide adenine dinucleotide phosphate-specific isocitrate dehydrogenase from Blastocladiella emersonii. 24 Aug 11

In order to obtain a quantitative estimate of the capacity of the pancreatic islets for provision of cytoplasmic acetyl-coenzyme A and for the turnover of nicotinamide adenine dinucleotide phosphate and its reduced form (NADP+/NADPH), the following enzymes were assayed in islets taken from New Zealand Obese mice: adenosine triphosphate citrate lyase (EC 4.1.3.8), malate dehydrogenase (decarboxylating) (NADP+) (EC 1.1.1.40), glutathione reductase (EC 1.6.4.2) and isocitrate dehydrogenase (NADP+) (EC 1.1.1.42). In addition, the activity of isocitrate dehydrogenase (NAD+) (EC 1.1.1.41) was determined. For comparative purposes the activities in exocrine pancreas, liver, heart muscle, kidney cortex and skeletal muscle were also determined. Specimens of pancreatic islets and the other tissues were microdissected from freeze-dried sections. In comparison with the other tissues, adenosine triphosphate citrate lyase was particularly active in the islets. The NADP+/NAPH-converting enzymes had activities, which suggested a rapid turnover of the islet NADP+/NADPH pool.
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PMID:Nicotinamide adenine dinucleotide phosphate-converting enzymes and adenosine triphosphate citrate lyase in some tissues and organs of New Zealand obese mice with special reference to the enzyme pattern of the pancreatic islets. 24 Aug 82

The binding of TPNH to native and chemically modified pig heart TPN-dependent isocitrate dehydrogenase was studied by the techniques of ultrafiltration and fluorescence enhancement. A single site (per peptide chain) was found for TPNH with a dissociation constant (KD = 1.45 muM) that is quantitatively comparable to the Michaelis constant. The oxidized coenzyme, TPN+, weakens the binding of TPNH. The substrate manganous isocitrate also inhibits the binding of TPNH and, reciprocally, TPNH inhibits the binding of manganous isocitrate, suggesting that binding to the reduced coenzyme and substrate sites is mutually exclusive. Ultrafiltration experiments with carbonyl [14C]TPN+ revealed the existence of two sites with a dissociation constant (49 muM) more than ten times higher than the Michaelis constant. This observation excludes a random mechanism for isocitrate dehydrogenase or a sequential mechanism in which TPN+ binds first. Four chemically modified isocitrate dehydrogenases have been prepared: enzyme inactivated by reaction of a single methionyl residue with iodoacetate, by modification of a glutamyl residue by glycinamide (in the presence of a water soluble carbodiimide), by reaction of four cysteines successively with 5,5'-dithiobis(2-nitrobenzoic acid) and potassium cyanide, or by addition of two cysteine residues to N-ethylmaleimide. These enzymes were tested for their ability to bind TPN+, TPNH, and manganous isocitrate. In the cases of the cysteinyl and glutamyl-modified enzymes, inactivation appears to be due primarily to loss of the ability to bind the substrate manganous isocitrate. In constrast, the methionyl residue may participate in the coenzyme binding site or, more likely, may be involved in a step in catalysis subsequent to binding.
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PMID:Coenzyme binding by native and chemically modified pig heart triphosphopyridine nucleotide dependent isocitrate dehydrogenase. 24 96

In an effort to demonstrate biochemical changes occuring in malperfused retinas, oxygen-induced retrolental fibroplasia was produced in kittens. Immediately before the onset of vasoproliferations, that is in the stage of maximal hypoxia, the activities of lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G-6-PDH), malate dehydrogenase (MDH) and isocitrate dehydrogenase (ICDH) were determined. The activity of MDH was found to be significantly decreased, whereas the activities of the other enzymes showed no major changes.
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PMID:Retinal enzyme activities under hypoxic conditions prior to neovascularization. 30 9


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