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

The interaction of the 2'-phosphate-containing nucleotides (NADP+, NADPH, 2'-phosphoadenosine 5'-diphosphoribose, and adenosine 2',5'-bisphosphate) with NADP+ -specific isocitrate dehydrogenase was studied by using 31P NMR spectroscopy. The separate resonances corresponding to free and bound nucleotides, characteristic for slow exchange of nuclei on the NMR time scale, were observed in the spectra of the enzyme (obtained in the presence of excess ligand) with NADP+ and NADPH in the absence and presence of Mg2+ and with 2'-phosphoadenosine 5'-diphosphoribose in the absence of metal or in the presence of the substrate magnesium isocitrate. The position of the 31P resonance of the bound 2'-phosphate group in these spectra is invariant (delta = 6) in the pH range 5-8, indicating that the pK of this group is much lower in the complexes with the enzyme than that (pK = 6.13) in the free nucleotides. The additional downfield shift of this resonance by 1.8 ppm beyond that (delta = 4.22) of the dianionic form of the 2'-phosphate in free nucleotides suggests interaction with a positively charged group(s) and/or distortion of P-O-P angles as the result of binding to the enzyme. A single resonance of 2'-phosphate was observed in the spectrum of the enzyme complex with 2'-phosphoadenosine 5'-diphosphoribose in the presence of Mg2+, with the chemical shift dependent on the nucleotide to enzyme ratio, characteristic for the fast exchange situation. Addition of metal does not perturb the environment of the 2'-phosphate in the complexes of NADP+ and NADPH with isocitrate dehydrogenase.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Phosphorus-31 nuclear magnetic resonance studies of the binding of nucleotides to NADP+-specific isocitrate dehydrogenase. 672 20

Changes in the activities of glucose-6-phosphate dehydrogenase [EC 1.1.1.49], 6-phosphogluconate dehydrogenase [EC 1.1.1.44] and cytoplasmic and mitochondrial "malic" enzyme [EC 1.1.1.40] and NADP+- linked isocitrate dehydrogenase [EC 1.1.1.42] were measured in the liver, heart, lung and brain during ontogenesis in the chicken. In the liver the cytoplasmic malic enzyme was constant during embryonal development, increasing suddenly and markedly thereafter and isocitrate dehydrogenase increased in the embryo and decreased after hatching while their mitochondrial isoenzymes showed parallel but less marked changes. Activities of the other dehydrogenases were essentially unchanged. In the heart only cytoplasmic isocitrate dehydrogenase showed important changes, increasing three-fold during growth after hatching. In the lung, glucose-6-phosphate dehydrogenase and cytoplasmic malic enzyme attained their maximum activities respectively at 16 to 18 d and 14 d of development. Mitochondrial malic enzyme did not change, while isocitrate dehydrogenase reached its maximum between 14 and 18 d. In the brain cytoplasmic malic enzyme was activated only after hatching, while its mitochondrial isoenzyme and isocitrate dehydrogenase showed discontinuous variations of an insignificant magnitude. Other activities were unchanged.
 ...
PMID:Changes in the activities of NADP+-linked dehydrogenases during ontogenesis in the chicken. 673 53

Lipogenic enzymes glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, isocitrate dehydrogenase NADP+ soluble and malic enzyme have been determined in the hepatic soluble fraction of rats chronically treated with ethanol and a lipid rich diet. The treatment based on protectives and lipotropic substances administered as nucleotides: UDP-glucose, CDP-choline, S-adenosyl methionine and Coenzyme A, elicits a significant restoration on the activities of G6PDH, 6PGDH and ICDH. These results show that the treatment, on promoting lipid mobilization, could increase the rate of hepatic lipogenesis. The malic enzyme enhanced activities, when ethanol and lipid diet were simultaneously administered, may be interpreted as a requirement for NADPH by the microsomic drug oxidation system.
 ...
PMID:[Effect of the administration of nucleotide coenzymes on the lipogenic enzyme changes caused by chronic alcohol intoxication]. 675 77

A NADP+-specific isocitrate dehydrogenase (EC 1.1.1.42) was isolated and purified over 400-fold from Anacystis nidulans. The enzyme activity responded slowly to rapid changes in ligand (NADP+, isocitrate, Mg2+-ions) or enzyme concentration as well as to rapid changes in temperature. These are properties characteristic of the hysteretic enzymes. In addition, the enzyme activity was subject to product (alpha-ketoglutarate) inhibition. ATP, ADP and CDP also inhibited the enzyme. Unlike several other cyanobacterial enzymes, the isocitrate dehydrogenase of Anacystis is not under redox control.
 ...
PMID:Isolation and properties of an isocitrate dehydrogenase from Anacystis nidulans. 679 15

This study has investigated the feasibility of calculating the cytoplasmic free [NADP+]/[NADPH] ratio in rat brain. The time course of the change in the substrate ratios of the malate dehydrogenase (decarboxylating) [E.C. 1.1.1.40], NADP+-isocitrate dehydrogenase (decarboxylating) [E.C. 1.1.1.42] and 6-phosphogluconate dehydrogenase (decarboxylating) [E.C. 1.1.1.44] reactions was followed for up to 10 min after a single, unmodified electroconvulsive seizure. From the results it has been concluded that during periods of low flux, the direction and magnitude of the change in the cytoplasmic free [NADP+]/[NADPH] ratio can, in fact, be reasonably determined even though there is some uncertainty in the absolute value of the ratio itself. It is recommended that reliance not be placed on a single enzyme system but that one or both of the other systems also be observed under a given experimental condition to increase confidence in the determination. The results also demonstrate that seizure and anoxia have a far lesser effect on the cytoplasmic free [NADP+]/[NADPH] ratio than on the free [NAD+]/[NADH] ratio in the same compartment. These results suggest that the pathways using the nicotinamide-adenine dinucleotide phosphate system are relatively protected from the rapid fluctuations that seizure and anoxia can produce.
 ...
PMID:The calculation of the cytoplasmic free [NADP+]/[NADPH] ratio in brain: effect of electroconvulsive seizure. 679 9

The specific activities of testicular enzymes of the pyruvate/malate cycle involved in lipogenesis after thyroidectomy and thyroxine replacement were studied in prepubertal, pubertal and adult rats. Thyroidectomy induced testicular ATP citrate-lyase, malate dehydrogenase and malic enzyme activities and inhibited isocitrate dehydrogenase (NADP+) activity. Thyroxine treatment on thyroidectomized animals reverted all enzyme activities to normal. The result suggests that thyroid hormones have a differential effect on testicular enzymes of the pyruvate/malate cycle involved in lipogenesis.
 ...
PMID:Effect of thyroidectomy on testicular enzymes of the pyruvate/malate cycle involved in lipogenesis. 682 30

The total and specific activity of 3 beta-hydroxy-delta 5-steroid dehydrogenase, isocitrate dehydrogenase (NADP+) and glucose-6-phosphate dehydrogenase were measured in ovarian follicles from the domestic fowl. The enzymes were assayed in the five largest yolk-filled follicles which were sampled twice during the ovulatory cycle, at 1 h and 16 h before an expected ovulation. The total and specific activity of granulosa enzymes increased throughout the hierarchy and reached a maximum in the largest follicle. The relative increase in 3 beta-hydroxy-delta 5-steroid dehydrogenase activity was greater than that of the other two enzymes examined. The total thecal 3 beta-hydroxy-delta 5-steroid dehydrogenase activity reached a maximum in the third and fourth largest follicles. Thereafter its activity decreased up to the time of ovulation. The activity of 3 beta-hydroxy-delta 5-steroid dehydrogenase and glucose-6-phosphate dehydrogenase in follicles collected 1 h before and ovulation were significantly less than the activity in corresponding follicles collected 16 h before an ovulation.
 ...
PMID:3 beta-hydroxy-delta 5-steroid dehydrogenase activity in the rapidly growing ovarian follicles of the domestic fowl (Gallus domesticus). 695 61

A number of differences in the kinetic and physical properties of the Escherichia coli nicotinamide adenine dinucleotide phosphate (NADP+) dependent malic enzyme have been found, depending upon whether Mg2+ or Mn2+ served to fulfill the divalent cation requirement. The velocity-NADP+ and velocity-cation saturation curves exhibit a simple hyperbolic response in the presence of either metal cofactor, but the affinity for NADP+ (and malate) as well as the Vmax is increased in the presence of Mn2+. The high affinity of the enzyme for Mn2+ coupled with the increased affinity for substrates indicates that Mn2+ is the preferred cofactor in vitro. With either Mg2+ or Mn2+ as cation, the velocity-malate saturation curves in the absence of effectors are complex at pH 7.45, indicating varying combinations of apparent positive and negative cooperative behavior. Greater initial positive cooperative behavior between malate binding sites is observed with Mg2+ as cation. The enzyme appears to be equally sensitive to inhibition by the allosteric inhibitors reduced nicotinamide adenine dinucleotide (NADH) and oxaloacetic acid (OAA) in the presence of either cation, but the interaction between malate binding sites, in the presence of effectors, varies significantly with the choice of metal cofactor. The inhibitor NADH increases the interaction between malate binding sites in the presence of Mn2+ but has little effect on subunit interaction in the presence of Mg2+. The inhibitor OAA increases the interaction between malate binding sites in the presence of both cations, with increased positive cooperativity observed with Mn2+ but increased negative cooperativity with Mg2+. The kinetic data can be explained by a model involving sequential ligand-induced conformational changes of the enzyme, resulting in a mixture of apparent positive and negative cooperative behavior. Alternative explanations involving different classes of noninteracting binding sites or different enzyme forms are also considered. The metal cofactors, Mg2+ and Mn2+, appear to stabilize two distinct conformational states of the enzyme which differ in response to varying substrate and effector concentrations. Altered conformational states of the enzyme in the presence of the two cations are further substantiated by proteolytic digestion studies with the homogeneous enzyme. The results are strikingly similar to previous results reported on the nicotinamide adenine dinucleotide (NAD+) dependent malic enzyme and the NAD+-dependent isocitrate dehydrogenase, supporting the suggestion that metal cofactors function as regulatory entities.
 ...
PMID:Role of metal cofactors in enzyme regulation. Differences in the regulatory properties of the Escherichia coli nicotinamide adenine dinucleotide phosphate specific malic enzyme, depending on whether magnesium ion or manganese ion serves as divalent cation. 701 78

Two forms of NADP-specific isocitrate dehydrogenase (threo-DS-isocitrate: NADP+ oxidoreductase (decarboxylating), EC 1.1.1.42) in Escherichia coli have been resolved by polyacrylamide gel isoelectric focusing and electrophoresis. Incubation of the enzyme with Mn2+ plus isocitrate prior to focusing resulted in the formation of an additional form of the enzyme, presumably the enzyme-manganese-isocitrate complex. Glycerol, a cryoprotectant used to stabilize the enzyme during purification and storage, also stabilized in during focusing, but was not necessary during electrophoresis. Thin-layer gel filtration did not reveal any differences in molecular weight between the different species of isocitrate dehydrogenase.
 ...
PMID:NADP-specific isocitrate dehydrogenase from Escherichia coli. V. Multiple forms of the enzyme. 702 43

Suspensions of enzymatically prepared hepatocytes from starved rats were separated according to their buoyant density at 12 degrees C in linear, isosmotic gradients of metrizamide, centrofuged at low speed for a relatively short time. The recovery of cell protein was 86%. Hepatocytes of high viability formed a single band around 1.10 g/cm3 and were recovered as four density populations (P1-P4) form low to high density, respectively. The content of protein was significantly lower in population P1, while the content of neutral fat or the averaged cell size was similar in the various populations. The specific activity of alanine aminotransferase increased in the order P1-P4. The distribution of this enzyme within the intact liver acinus obtained by others indicate that a partial separation of periportal and perivenous hepatocytes had occurred. The activity patterns of lactate dehydrogenase, glutamate dehydrogenase, isocitrate dehydrogenase (NADP+) and pyruvate kinase, also with known intra acinar distributions, supported this conclusion. The hepatocytes showed signs of shrinkage after separation, but since they retained a normal ultrastructure, most enzyme activities and viability, the present technique was regarded superior to previous procedures of hepatocyte separation by density. The degree of separation was calculated from an equation (see Appendix), and the periportal/perivenous ratio for parameters measured in density populations can be obtained. The specific activity of phosphofructokinase, alcohol dehydrogenase and aldehyde dehydrogenase showed no differences between populations. However, the ratio high-Km/low-Km aldehyde dehydrogenase increased in the order P4-P1.
 ...
PMID:Partial separation and biochemical characteristics of periportal and perivenous hepatocytes from rat liver. 702 82


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