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)

Liver injury was induced by a single dose (60 mg/kg) of cocaine in male albino Swiss mice untreated or pretreated with phenobarbital (in drinking water 1 gm/L), for 5 days before cocaine administration. One parameter of liver injury, serum isocitrate dehydrogenase activity, showed sharp increases at 24 hr of cocaine treatment; we also noted decrease hepatic levels of ATP, GSH, cytochrome P-450 and NADPH/NADP+ ratio and increases in malondialdehyde concentration. Histopathological study of liver slices showed perivenous and periportal necrosis induced by cocaine in untreated mice and mice pretreated with phenobarbital, respectively. A regenerative postnecrotic response, which peaked at 48 hr, was demonstrated by the appearance of mitotic cells. Mitotic index analysis showed that proliferative cells appear to be unevenly distributed in the hepatic acinus and were mainly located in the vicinity of the damaged acinar region. Genomic DNA ploidy and the distribution of DNA in the phases of the cell cycle were studied in nuclei of isolated hepatocytes. At 12 hr of cocaine administration, both in untreated and phenobarbital-pretreated mice, the following changes were observed: a sharp decrease in tetraploid (4N) cells (40% to 17% and 25% to 6%, respectively) and octoploid (8N) cells (5% to 2% and 2% to 1%, respectively), together with the appearance of a hypodiploid population (13% and 31%, respectively). Hypodiploid population was characterized as apoptotic cells by detection of DNA fragmentation in agarose gel. These results suggest that a significant percentage of cell death induced by cocaine occurs by means of the apoptosis death program. Comparison of the initial values of DNA ploidy with those obtained at 7 days of cocaine administration showed remarkable increases in polyploid populations (4N and 8N) and a decrease in diploid cells (2N), indicating that the process of differentiation occurs when liver restores its functionality.
...
PMID:Cocaine-induced liver injury in mice elicits specific changes in DNA ploidy and induces programmed death of hepatocytes. 792 41

The cytosolic form of NADP+: isocitrate dehydrogenase, a primary source of the NADPH required for de novo fatty acid synthesis in lactating bovine mammary gland, was studied to determine possible mechanisms of regulation by metabolites. The enzymatic reduction of NADP+ exhibits lag-burst (hysteretic) kinetics that are eliminated by the noncatalytic binding of the substrate, a complex (1:1) of a metal ion (Mn2+ or Mg2+) and isocitrate. Preincubation of the enzyme with metal-citrate complex also nearly abolished the lag or activation time. In steady-state experiments, analyses of velocity versus metal-citrate complex as a binding isotherm, following the assumptions of Wyman's theory of thermodynamic linkage, showed that binding of metal-citrate complex could both stimulate and inhibit the enzyme. This analysis suggested hyperactivation by binding to sites with an average dissociation constant of .25 mM, inhibition by binding to sites with an average dissociation constant of 3.83 mM, and modulation (reactivation) by binding to sites with an average dissociation constant of 1.54 mM. Conformational changes induced by the binding of ligands were assessed using circular dichroism. The results suggest that binding of metal-isocitrate induces a conformational transition involving tyrosyl residues that is related to the altered kinetic processes. Reexamination of Michaelis-Menten kinetics using non-linear regression analysis also demonstrated hyperactivation of enzyme activity by metal-isocitrate with a dissociation constant equal to 21 microM (which is nearly seven times greater than the Michaelis constant). Concentration ranges observed for these transitions are compatible with physiological conditions, suggesting that complexes of metal-citrate and metal-isocitrate serve to modulate the activity of NADP+: isocitrate dehydrogenase.
...
PMID:Regulation of the soluble form of nicotinamide adenine dinucleotide phosphate-specific isocitrate dehydrogenase from lactating bovine mammary gland: effects of metabolites on activity and structure. 813 88

A new enzymatic method for assaying iron in serum samples, suitable for automated analyzers, is reported. Three reagent mixtures are used: dilution buffer (pH 3.0; ascorbate), reagent 1 (pH 6.7; apoaconitase), and reagent 2 (pH 7.7; citrate, magnesium, and isocitrate dehydrogenase). Sera are diluted with dilution buffer. Fe3+ is liberated from transferrin in sera under acidic conditions, and then reduced by ascorbate. Reagent 1 is added to diluted specimens, and apoaconitase is reactivated by Fe2+ at neutral pH. The resulting solutions are mixed with reagent 2, so that holoaconitase hydrolyzes citrate to isocitrate and the isocitrate and NADP+ are converted to 2-oxoglutarate, NADPH, and CO2. Serum iron is determined linearly up to 70 mumol/L, with within-run CVs < or = 2.4% and day-to-day CVs < or = 2.9%. This method (y) gives results correlating with those of a Reference Method (x) proposed by the International Committee for Standardization in Haematology: y = 0.98x + 0.38 mumol/L (n = 72, r = 0.996, Sylx = 0.63 mumol/L). The mean (+/- SD) serum iron concentrations measured by our method were 18.5 +/- 5.4 and 15.2 +/- 6.0 mumol/L for 63 males and 166 females, respectively.
...
PMID:New enzymatic assay of iron in serum. 817 49

We describe an improved enzymatic ultraviolet absorbance method for assaying creatinine in serum, plasma, and urine. Creatinine is hydrolyzed by creatinine iminohydrolase (EC 3.5.4.21) to ammonia and N-methylhydantoin. The ammonia produced combines with 2-oxoglutarate and NADPH in the presence of glutamate dehydrogenase to yield glutamate and NADP+. The consumption of NADPH, measured by a two-point fixed-time assay, is proportional to the amount of creatinine in the sample. The assay is carried out in two steps: The first step eliminates background absorbance in hyperlipemic samples and endogenous ammonia through a "clearing system" and an isocitrate dehydrogenase-based "ammonia scavenger system"; the second step starts creatinine measurement. The method affords a simple, rapid, and sensitive assay with good precision and extended linearity; it employs working solutions stable at least 4 months. Test results compare closely with those of the isotope dilution-mass spectrometry Definitive Method, the HPLC procedure, and the fuller's earth method. The proposed method is not subject to interference from several metabolites or from the 72 drugs tested. Because it is easily automated, the method is suitable for routine work in clinical laboratories.
...
PMID:A step forward in enzymatic measurement of creatinine. 828 20

Dehydroepiandrosterone (DHEA) treatment of rats decreases gain of body weight without affecting food intake; simultaneously, the activities of liver malic enzyme and cytosolic glycerol-3-P dehydrogenase are increased. In the present study experiments were conducted to test the possibility that DHEA enhances thermogenesis and decreases metabolic efficiency via transhydrogenation of cytosolic NADPH into mitochondrial FADH2 with a consequent loss of energy as heat. The following results provide evidence which supports the proposed hypothesis: (a) the activities of cytosolic enzymes involved in NADPH production (malic enzyme, cytosolic isocitrate dehydrogenase, and aconitase) are increased after DHEA treatment; (b) cytosolic glycerol-3-P dehydrogenase may use both NAD+ and NADP+ as coenzymes; (c) activities of both cytosolic and mitochondrial forms of glycerol-3-P dehydrogenase are increased by DHEA treatment; (d) cytosol obtained from DHEA-treated rats synthesizes more glycerol-3-P during incubation with fructose-1,6-P2 (used as source of dihydroxyacetone phosphate) and NADP+; the addition of citrate in vitro further increases this difference; (e) mitochondria prepared from DHEA-treated rats more rapidly consume glycerol-3-P added exogenously or formed endogenously in the cytosol in the presence of fructose-1,6-P2 and NADP+.
...
PMID:Concerning the mechanism of increased thermogenesis in rats treated with dehydroepiandrosterone. 834 75

The structure of isocitrate dehydrogenase (IDH) with a bound complex of isocitrate, NADP+, and Ca2+ was solved at 2.5-A resolution and compared by difference mapping against previously determined enzymatic complexes. Calcium replaces magnesium in the binding of metal-substrate chelate complex, resulting in a substantially reduced turnover rate. The structure shows the following: (i) A complete, structurally ordered ternary complex (enzyme, isocitrate, NADP+, and Ca2+) is observed in the active site, with the nicotinamide ring of NADP+ exhibiting a specific salt bridge with isocitrate. The binding of the cofactor nicotinamide ring is dependent on this interaction. (ii) Isocitrate is bound by the enzyme with the same interactions as those found for the magnesium/substrate binary complex, but the entire molecule is shifted in the active site by approximately 1 A in order to accommodate the larger metal species and to interact with the nicotinamide ring. The distances from isocitrate to the bound calcium are substantially longer than those previously found with magnesium. (iii) NADP in the Escherichia coli IDH has a novel binding site and conformation as compared to previously solved dehydrogenases. (iv) The orientation and interactions of the nicotinamide ring with the substrate are consistent with the stereospecificity of the enzyme-catalyzed reaction.
...
PMID:Structure of isocitrate dehydrogenase with isocitrate, nicotinamide adenine dinucleotide phosphate, and calcium at 2.5-A resolution: a pseudo-Michaelis ternary complex. 836

A two-step method for assaying creatinine in serum and urine samples, suitable with automated analyzers, is reported. Reagent 1, for the first step, contains a blanking system [creatine amidinohydrolase (CRTase), urease, glutamate dehydrogenase, NADPH, and 2-oxoglutarate] and a NADPH-regenerating system [Mg(2+)-dependent isocitrate dehydrogenase (ICD), MgCl2, and excess isocitrate]. Reagent 2, for the second step, contains the metal-chelating reagent trans-1,2-cyclohexanediamine-N,N,N',N'-tetraacetic acid (CyDTA) and a trigger system [creatinine amidohydrolase (CRNase)]. When a specimen is mixed with reagent 1, all the creatine, urea, and NH3 present are removed by the blanking and NADPH systems. On adding reagent 2, CyDTA inactivates ICD to inhibit the NADPH system. Simultaneously, the creatinine (1 mol) in the specimen is hydrolyzed into creatine by CRNase, and then releases NADP+ (2 mol) through the blanking system. Our optimized method can determine creatinine linearly up to 500 mg/L, with within-day CVs < 1.2% and day-to-day CVs < 2.7%.
...
PMID:Enzymatic rate assay of creatinine in serum and urine. 840 98

Incubation of rat liver cytosolic isocitrate dehydrogenase with N-ethylmaleimide (NEM) resulted in the inactivation of the enzyme following pseudo-first order kinetics. Isocitrate affords considerable protection against inactivation whereas NADP+ enhances modification of the enzyme, suggesting localization of the modified group at the active site. Correlation of loss of activity with incorporation of [14C]NEM indicated that two sulphydryl residues/sub-unit are modified of which only one is shown to be involved in catalysis. pH dependence of the inactivation process implicates a reactive group of pKa 8.1 in catalysis. We conclude that a unique cysteine residue is essential for maximal catalytic activity of isocitrate dehydrogenase.
...
PMID:Chemical modification of rat liver cytosolic NADP(+)-linked isocitrate dehydrogenase by N-ethylmaleimide. Evidence for essential sulphydryl groups. 848 57

We previously demonstrated that feeding rats the Steenbock and Black rickets-inducing diet produces remarkable changes in the metabolic pattern of intestinal mucosa, kidney, liver, cerebral cortex and heart. We have now determined the levels of calcium, phosphorus and citrate in cerebral cortex and the activity of some enzymes in synaptosomes and cerebral cortex mitochondria of three rat groups: control (Group A), fed a vitamin D-deficient diet (Group B), fed a vitamin D-deficient diet and treated with 1,25-dihydroxyvitamin D3 (Group C). While calcium content increased in Groups B and C, phosphorus concentration increased only in Group C and citrate in Group B in comparison with control. The increase in acetylcholinesterase and citrate synthase registered in Group B was restored to control values by 1,25-dihydroxyvitamin D3 treatment, while, neither the decrease in cytochrome c oxidase, nor the increase in glucose-6-phosphate dehydrogenase, acid phosphatase and NADP+(-)isocitrate dehydrogenase observed in Group B were corrected by 1,25-dihydroxyvitamin D3 supply. Acyl phosphatase showed a remarkable increase in consequence of 1,25-dihydroxyvitamin D3 administration.
...
PMID:Vitamin D--related modification of enzyme activities in synaptosomes and mitochondria isolated from rat cerebral cortex. 862 85

An 18.5-kb DNA fragment was cloned from Sphingomonas yanoikuyae (Sy) B1 (previously Beijerinckia B1). Analysis of a 4.3-kb sequence revealed an isocitrate dehydrogenase (Idh)-encoding gene (idhA), an unidentified open reading frame (ORF) and a partial glucosamine synthetase-encoding ORF (glmS). As in a number of bacteria, Tn7 insertion was found specifically at a site past the stop codon of glmS. The predicted 406-amino-acid sequence of IdhA shows, for the first time, an extensive sequence identity (66%) with an eukaryotic NADP+-specific Idh. The idhA gene was expressed in Escherichia coli. Identical restriction fragments carrying idhA were found in B1, Sy IFO15102 and Sy Q1 (formerly S. paucimobilis Q1), indicating a well-conserved idh gene.
...
PMID:Sequence and expression of an isocitrate dehydrogenase-encoding gene from a polycyclic aromatic hydrocarbon oxidizer, Sphingomonas yanoikuyae B1. 862 59


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

---