NADP-isocitrate Dehydrogenase Research Articles

Organic acid metabolism in Citrus grandis leaves and roots is differently affected by nitric oxide and aluminum interactions

‘Sour pummelo’ ( Citrus grandis) seedlings were irrigated for 18 weeks with nutrient solution containing 0 (−Al) and 1.2 mM (+Al) AlCl 3·6H 2O × 0, 10 and 500 μM sodium nitroprusside (SNP), a nitric oxide (NO) donor. Leaf malate content did not significantly change in response to SNP with or without aluminum (Al) except for an increase under 1.2 mM Al + 10 μM SNP, while leaf citrate content decreased with increasing SNP supply. Root malate content kept unchanging with or without Al except for an increase under 500 μM SNP in the absence of Al, while SNP-treated roots had a higher or similar citrate content. Al decreased or did not affect malate content in roots and leaves, and citrate content in roots, but increased leaf citrate content. Al-treated roots and leaves displayed lower or similar activities of acid-metabolizing enzymes [phospho enolpyruvate carboxylase (PEPC), NAD-malate dehydrogenase (NAD-MDH), NADP-malic enzyme (NADP-ME), citrate synthase (CS), aconitase (ACO), NADP-isocitrate dehydrogenase (NADP-IDH), phospho enolpyruvate phosphatase (PEPP) and pyruvate kinase (PK)] except that they had higher or similar activities of NADP-ME and PK and Al-treated leaves had a higher or similar activity of PEPP. In conclusion, the OA metabolism in leaves and roots is differently affected by NO and Al interactions.

Effects of melatonin on the activity of the glutathione antioxidant system and various NADPH-generating enzymes in the liver and blood of rats with type 2 diabetes mellitus

The actions of melatonin on the activity of the glutathione antioxidant system and various NADPH-generating enzymes in rats with type 2 diabetes mellitus were studied. The development of this pathology was found to be accompanied by increases in the activities of glutathione reductase (E.C. 1.6.4.2), glutathione peroxidase (E.C. 1.11.1.9), and NADP-isocitrate dehydrogenase (NADP-IDH, E.C. 1.1.1.41), along with decreases in the activity of glucose-6-phosphate dehydrogenase (G6PDH, E.C. 1.1.1.49) in both the liver and serum as compared with animals without pathology. In addition, there was a decrease in the level of reduced glutathione. Administration of melatonin induced changes in the study parameters towards control values. This effect appeared to be linked to decreases in the loading on the glutathione antioxidant system due to the antioxidant properties of this hormone, which are associated with the features of its chemical structure which allow it to interact efficiently with free radicals to form metabolites with little or no toxicity.

Effects of 2,4-Dimethoxyphenyl Biguanide on Glutathione System Activity in Rat Tissues in Brain Ischemia–Reperfusion

We studied the effects of dimethoxyphenyl biguanide on glutathione peroxidase and glutathione reductase activities, level of reduced glutathione in rat tissues, and activity of some NADPH-regenerating enzymes (glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase) under conditions of ischemia-reperfusion of the brain. Administration of this biguanide derivative under pathological conditions led to a decrease in the analyzed parameters (elevated under conditions of ischemia-reperfusion) in the serum and brain tissue. The results attest to less pronounced mobilization of the glutathione system (compared to pathological state) due to antioxidant and protective properties of 2,4-dimethoxyphenyl biguanide under conditions of ischemic tissue damage associated with oxidative stress.

Root release and metabolism of organic acids in tea plants in response to phosphorus supply

Self-rooted, 10-month-old, uniform tea [Camellia sinensis (L.) O. Kuntze cv. Huangguanyin] plants were supplied for 17 weeks with 0, 40, 80, 160, 400, or 1000μM phosphorus (P) to investigate the effects of P supply on root citrate and malate release, the concentrations of malate and citrate and the activities of acid-metabolizing enzymes in leaves and roots. Root malate release and accumulation was induced by both 0 and 40μM P, while root citrate release and accumulation was induced only by 0μM P. Phosphorus-deficiency-induced malate and citrate release coincided with higher concentrations of root malate and citrate. The higher concentrations of malate and citrate were accompanied by increased activities of phosphoenolpyruvate carboxylase (PEPC), phosphoenolpyruvate phosphatase (PEPP), citrate synthase (CS) and NAD-malic enzyme (NAD-ME) and decreased activities of pyruvate kinase (PK), NADP-ME and NADP-isocitrate dehydrogenase (NADP-IDH) in roots. In contrast to roots, malate accumulated in the leaves only in response to 0μM P, and no change was observed in citrate levels. The P-deficiency-induced leaf malate accumulation coincided with increased activities of NADP-ME, NAD-ME and PK. Overall, the P-deficiency-induced changes in organic acid (OA) metabolism differed between roots and leaves. The high tolerance of tea plants to P-deficiency might be involved in two major processes: (a) increasing the availability of P by inducing root release of OA anions; and (b) improving the ability to use P efficiently by inducing bypass enzymes involved in tissue P economy.

Elucidation of mechanisms underlying the protective effects of olive leaf extract against lead-induced neurotoxicity in Wistar rats

Recently, we identified that olive leaf extract (OLE) prevents lead (Pb)-induced abnormalities in behavior and neurotransmitters production in chronic Pb exposure in rats. The aim of the present study was to provide additional evidence that OLE acts as an anti-apoptotic, anti-inflammatory, and antioxidant mediator in Pb exposed rats. 4-weeks old Wistar rats were exposed or not to 250 mg/l Pb for 13-weeks and then exposed to tap water containing or not 0.1% OLE for additional 2-weeks. Atomic absorption spectrophotometry showed significantly elevated Pb levels in the hippocampus and serum and reaches 5 and 42 µg/mg tissue, respectively. In the hippocampus, the examination of markers of apoptosis and inflammation revealed an increase in caspase-3 activity and DNA fragmentation as well as tumor necrosis factor alpha, interleukin-1 beta and prostaglandin E2 in Pb-exposed rats. In addition, our findings showed that Pb induced 4-hydroxynonenal production and inhibited antioxidant-related enzyme activity, such as glutathione-S-transferase as wells as energy metabolism-related enzyme activity, such as NADP-isocitrate dehydrogenase and glucose transporter. Upon examination of signaling pathways involved in apoptosis process, we found that Pb induced p38 mitogen activated protein kinase (MAPK) and Akt phosphorylation, but in contrast, inhibited that of ERK(1/2). Interestingly, OLE administration diminished tissue Pb deposition and prevented all Pb effects. In the frontal cortex, our data also showed that OLE-abolished Pb-induced caspase-3 activity and DNA fragmentation. Collectively, these data support the use of OLE by traditional medicine to counter Pb neurotoxicity.

Catalytic Characteristics of NADP-Isocitrate Dehydrogenase from the Liver of Rats in Health and after Injection of TNF-α and Melatonin Treatment

Activity of NADP-dependent isocitrate dehydrogenase (EC 1.1.1.42) increases and the catalytic characteristics of the enzyme isolated from the liver of rats are changed under conditions of apoptosis induction in comparison with these characteristics in health. Injection of melatonin induced a trend to normalization of kinetic parameters of catalytic activity and of some regulatory characteristics of the enzyme.

Effect of dietary ascorbate on lipogenesis and lipolysis activities in black sea bream, Acanthopagrus schlegelii

To assess the effect of dietary ascorbate on lipid metabolism, 1-year black sea bream (Acanthopagrus schlegelii) were reared on a casein-based purified diet and an ascorbate fortified diet (1,100 mg of L: -ascorbyl-2- monophosphate-Mg/kg diet). The fortified ascorbate was effectively incorporated into the fish body and elevated muscle carnitine content. Fortifications of dietary ascorbate depressed activities of glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase as lipogenic enzymes in the hepatopancreas and intraperitoneal fat body. Starvation after feeding experiment activated carnitine palmitoyltransferase as a lipolysis enzyme in the hepatopancreas in both control and vitamin C(VC) groups, while the lipolysis activity was significantly higher in VC group. These results confirmed that dietary ascorbate depressed lipogenesis and activated lipolysis, i.e., influenced the lipid metabolism of black sea bream.

Expression and catalytic properties of rat liver NADP-isocitrate dehydrogenase under normal conditions, after administration of tumor necrosis factor-α and thioctic acid action

Development of apoptosis is accompanied by a decrease in transcripts of NADP-isocitrate dehydrogenase (NADP-ICDH, EC 1.1.1.42), and also by alterations of catalytic properties from the rat liver enzyme in comparison with control. Administration of thioctic acid increased the level of expression towards normal values. Molecular weight of homogenous preparations of NADP-ICDH purified from livers of control and experimental rats was the same 112 ± 5.8 kDa, however, Km values and pH-optimum changed during induction of apoptosis. Regulation of NADP-ICDH activity by some intermediates of the tricarboxylic acid cycle also differed in these groups.

Characterization of a Stress-induced NADP-isocitrate Dehydrogenase Gene in Maize Confers Salt Tolerance in Arabidopsis

In this paper, a full-length cDNA-encoding cytosolic nicotinamide adenine dinucleotide phosphate-dependent isocitrate dehydrogenase was isolated from maize and named ZmICDH. Analysis of the deduced protein sequence revealed that this gene had considerably high homologies with other plant ICDH genes such as those from rice, Arabidopsis and poplar. The gene was transcribed in all tissues tested, with the highest amount of transcript in root. Subcellular localization results indicated that ZmICDH was localized in cytosol. In an attempt to further understand the role of ZmICDH in maize, the functional characterization of the gene was conducted. The results indicated that the expression of ZmICDH was induced by drought and salt stresses. ZmICDH enhanced salt tolerance in transgenic Arabidopsis.

Rapid Dietary Protein Changes, Enzyme Activities, mRNAs and Plasma Hormones in the Broiler Chicken

Ross 708 broiler chickens were fed one of three levels of crude protein (12, 21 or 30%) from 7 to 28 days of age. Birds were then switched to either a higher (30%) or lower level of crude protein (12% and sampled three days following the switch. The purpose of these treatments was to test effects of changes in protein level at a representative time during the finisher phase (days 28 to 31) of broiler growth and to relate changes to metabolic plasma hormone levels (IGF-I, IGF-II, insulin, leptin, T3, T4, glucagons, Ghrelin) and regulatory enzymes [malic enzyme (ME), aspartate aminotransferase (AAT), and NADP-isocitrate dehydrogenase (ICD)] and their respective mRNAs The data from this experiment show that a priority of hormones can be established with respect to correlations between circulating values and representative metabolic enzymes and their mRNAs. It is suggested from these data that both IGF-I and T4 are equal in a metabolic priority scheme and are superior to glucagon and Ghrelin which are still significantly related to certain enzymes and their mRNAs. It is entirely possible that mRNA levels do not correlate or totally regulate enzyme protein (as evidenced by activities of regulatory enzymes) although the relationships for ME (R = 0.69; P<0.001), ICD (R = 0.64; P <0.001) and AAT (R = 0.47, P<0.001) does lend some credence that transcriptional events regulate these two enzymes.

Expression and catalytic properties of rat liver nadp-isocitrate dehydrogenase under normal conditions, after administration of tumor necrosis factor-α and at thioctic acid action

Development of apoptosis is accompanied by a decrease in transcripts of NADP-isocitrate dehydrogenase (NADP-IDH, E.C. 1.1.1.42.), and also alterations of catalytic properties from the rat liver enzyme in comparison with control. Administration of thioctic acid is increased the level of expression towards normal values. Enzyme preparations NADP-IDH were obtained from rat liver at norm conditions, after introduction of tumor necrosis factor and thioctic acid action under apoptosis. Molecular weight of homogenous preparations of NADP-IDH purified from livers of control and experimental rats was 112±5,8 kDa, however Km values and pH-optimum changed in apoptosis. Regulation of NADP-IDH activity under effect of some intermediates of the tricarboxylic acid cycle also differed in these groups.

Purification of NADP-Isocitrate dehydrogenase from Red Kidney beans (Phaseolus vulgaris rogue)

Nicotinamide adenine dinucleotide phosphate-dependent isocitrate dehydrogenase (NADP+-IDH; EC 1.1.1.42) was extracted from red kidney beans (Phaseolus vulgaris.) after the beans were placed into Murashige-Skoog medium and incubated under continuous white light (110 μmol photon m−2 s−1), then filtered, centrifuged and the supernatant was used for purification. The enzyme purified using ammonium sulphate precipitation, DEAE-cellulose and Matrex Bio red A (dye-ligand-chromatography) techniques, and exhibits several bands through electrophoresis, with one band corresponds to the IDH activity. Km values for the enzyme was 55.71± 4.56 x 10-6M. The enzyme has an optimum pH at 8.5, and optimum temperature at 30°C. The enzyme can be stable at RT (about 25°C) for 180min, but the activity disappears at 400min. Enzyme activity appears to be independent of divalent metals in deionized water, but the addition of Mg+2 and Mn+2 by 4.5 and 2-folds respectively. The purified enzyme was injected into white rabbits to raise an antiserum against NADP+-IDH. The specificity of the antiserum was assayed by its ability to decrease the NADP+-IDH activity present in the extract. NADP+-IDH activity decreased when the extract was incubated with increasing volumes of the antiserum obtained.

Changes in organic acid metabolism differ between roots and leaves of Citrus grandis in response to phosphorus and aluminum interactions

Seedlings of sour pummelo (Citrus grandis) were irrigated daily for 18 weeks with nutrient solution containing four phosphorus (P) levels (50, 100, 250 and 500 microM KH2PO4) and two aluminum (Al) levels [0 (-Al) and 1.2 mM AlCl3 x 6H2O (+Al)]. Both malate and citrate concentrations in +Al leaves decreased with increasing P supply, but their concentrations in -Al leaves did not change in response to P supply. The concentrations of malate under 50 microM P and of citrate under 50 and 100 microM P were higher in +Al leaves than in -Al ones, but malate concentration was lower in +Al leaves than in -Al ones under 500 microM P. There was no difference in root malate and citrate concentrations among different P and Al combinations except for an increase in malate and citrate under 50 microM P+0 mM Al and a slight decrease in malate under 50 microM P+1.2 mM Al. The activities of acid-metabolizing enzymes (citrate synthase, aconitase, phosphoenolpyruvate carboxylase, NADP-isocitrate dehydrogenase, phosphoenolpyruvate phosphatase, NAD-malate dehydrogenase, NADP-malic enzyme and pyruvate kinase) in most cases were less affected by P and Al interactions in roots compared to the leaves. Our results support the hypothesis that changes in organic acid metabolism differ between roots and leaves of C. grandis in response to P and Al interactions.

Decreased levels of metabolic enzymes in pancreatic islets of patients with type 2 diabetes

Glucose-stimulated insulin secretion is defective in patients with type 2 diabetes. We sought to acquire new information about enzymes of glucose metabolism, with an emphasis on mitochondrial enzymes, by comparing pancreatic islets of type 2 diabetes patients with those of non-diabetic controls. Expression of genes encoding 13 metabolic enzymes was estimated with microarrays and activities of up to nine metabolic enzymes were measured. The activities of the mitochondrial enzymes, glycerol phosphate dehydrogenase, pyruvate carboxylase (PC) and succinyl-CoA:3-ketoacid-CoA transferase (SCOT) were decreased by 73%, 65% and 92%, respectively, in the diabetic compared with the non-diabetic islets. ATP citrate lyase, a cytosolic enzyme of the mitochondrial citrate pyruvate shuttle, was decreased 57%. Activities of propionyl-CoA carboxylase, NADP-isocitrate dehydrogenase, cytosolic malic enzyme, aspartate aminotransferase and malate dehydrogenase were not significantly different from those of the control. The low activities of PC and SCOT were confirmed with western blots, which showed that their protein levels were low. The correlation of relative mRNA signals with enzyme activities was good in four instances, moderate in four instances and poor in one instance. In diabetic islets, the mRNA signal of the islet cell-enriched transcription factor musculoaponeurotic fibrosarcoma oncogene homologue A, which regulates expression of islet genes, including the PC gene, was decreased to 54% of the control level. PC activity and protein levels in the non-diabetic islets were significantly lower than in islets from non-diabetic rodents. Low levels of certain islet metabolic enzymes, especially mitochondrial enzymes, are associated with human type 2 diabetes.

NADP‐dehydrogenases from pepper fruits: effect of maturation

NADPH is an important molecule in the redox balance of the cell. Pepper fruits are the second worldwide consumable vegetables and exhibit different phenotypes after maturation. In this paper, two pepper cultivars were studied: Vergasa whose fruits shift from green to red after maturation, and Biela that shifts to yellow. Using fresh fruits from the same plants of the two cultivars at distinct maturation stages, the activity and gene expression of the main NADPH-generating dehydrogenases was studied. The activity analysis of the main NADP-dehydrogenases, glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), NADP-isocitrate dehydrogenase (NADP-ICDH) and NADP-malic enzyme (NADP-ME), showed that, except for the G6PDH, all the activities were enhanced (54-100%) in the mature pepper fruits from both cultivars (red or yellow) with respect to green pepper fruits. The content of NADPH and NADP in the mature fruits of both cultivars showed a noteworthy increase with respect to green fruits. For the transcript analysis, a partial cDNA of each NADP-dehydrogenase was obtained, and the NADP-ME was the only NADP-dehydrogenase that showed a significant induction. The increase in the content of NADPH in mature fruits because of the enhanced activity of NADP-dehydrogenases suggests that these NADPH-generating enzymes could be involved in the maturation of pepper fruits.

Активность глутатионовой антиоксидантной системы при гипертиреозе и при действии мелатонина

When hyperthyroidism develops, there are increases in the level of reduced glutathione and in the activities of glutathione peroxidase (GP) and glutathione reductase (GR) in the rat liver, heart, and serum. The activity of glucose-6-phosphate dehydrogenase (G-6-PDH) also increases, which is likely to be associated with the necessity of delivering of NADPH for the GP/GR system. The activity of NADP isocitrate dehydrogenase (IDН) changes slightly. With administration of melatonin for thyrotoxicosis, the content of reduced glutathione Increases in the examined tissues to a greater extent, the activities of GP and GR become normal. With melatonin being administered in hyperthyroidism, the changes in G-6-PDH and IDH activities are tissue-specific and more pronounced for G-6-PDH. Melatonin appears to act as an adaptogen that regulates the activity of the glutathione system and NADPH-generating enzymes in accordance with the influence of pathogenic factors on the body.

Is the Alkaline Tide a Signal to Activate Metabolic or Ionoregulatory Enzymes in the Dogfish Shark (Squalus acanthias)?

Experimental metabolic alkalosis is known to stimulate whole-animal urea production and active ion secretion by the rectal gland in the dogfish shark. Furthermore, recent evidence indicates that a marked alkaline tide (systemic metabolic alkalosis) follows feeding in this species and that the activities of the enzymes of the ornithine-urea cycle (OUC) for urea synthesis in skeletal muscle and liver and of energy metabolism and ion transport in the rectal gland are increased at this time. We therefore evaluated whether alkalosis and/or NaCl/volume loading (which also occurs with feeding) could serve as a signal for activation of these enzymes independent of nutrient loading. Fasted dogfish were infused for 20 h with either 500 mmol L(-1) NaHCO3 (alkalosis + volume expansion) or 500 mmol L(-1) NaCl (volume expansion alone), both isosmotic to dogfish plasma, at a rate of 3 mL kg(-1) h(-1). NaHCO3 infusion progressively raised arterial pH to 8.28 (control = 7.85) and plasma [HCO3-] to 20.8 mmol L(-1) (control = 4.5 mmol L(-1)) at 20 h, with unchanged arterial P(CO2), whereas NaCl/volume loading had no effect on blood acid-base status. Rectal gland Na+,K+-ATPase activity was increased 50% by NaCl loading and more than 100% by NaHCO3 loading, indicating stimulatory effects of both volume expansion and alkalosis. Rectal gland lactate dehydrogenase activity was elevated 25% by both treatments, indicating volume expansion effects only, whereas neither treatment increased the activities of the aerobic enzymes citrate synthase, NADP-isocitrate dehydrogenase, or the ketone body-utilizing enzyme beta-hydroxybutyrate dehydrogenase in the rectal gland or liver. The activity of ornithine-citrulline transcarbamoylase in skeletal muscle was doubled by NaHCO3 infusion, but neither treatment altered the activities of other OUC-related enzymes (glutamine synthetase, carbamoylphosphate synthetase III). We conclude that both the alkaline tide and salt loading/volume expansion act as signals to activate some but not all of the elevated metabolic pathways and ionoregulatory mechanisms needed during processing of a meal.

Mutations of the β‐subunit of human NAD‐specific isocitrate dehydrogenase in patients with Retinitis Pigmentosa

Mitochondrial NAD‐ and NADP‐isocitrate dehydrogenases (IDH) are crucial in the Krebs cycle. NAD‐IDH is composed of 3 subunits in the ratio 2α:1β:1γ and is allosterically regulated by ADP, by lowering the Km‐isocitrate. Two individuals with autosomal recessive Retinitis Pigmentosa (RP), but no other major symptoms, are homozygous for mutations in the β‐subunit of NAD‐IDH: the missense βL98P, and a 1‐basepair deletion in codon βI163 (ATT to –TT) resulting in a frameshift and premature termination of the β‐subunit. The activities of NAD‐ and NADP‐IDH were evaluated in extracts of lymphoblasts from unaffected individuals, heterozygote carriers of the mutations, and two RP patients. The NADP‐IDH activity was normal in all samples. In contrast, both homozygotes exhibited a Km‐NAD 260–300 times normal, while the Km‐NAD of the heterozygote samples was 4‐8 times that of normal. When ADP is added, Km‐isocitrate decreases only 3‐fold in the RP patient with the I163delA mutation, unlike normals in which ADP decreases Km‐isocitrate 9‐fold. This allosteric effect is completely lost in the homozygote βL98P mutant. The results show that these beta mutations primarily affect the enzyme's NAD affinity and ADP response. NADP‐IDH is the dominant mitochondrial IDH expressed in most tissues, while NAD‐IDH predominates in the eye. This differential expression may explain why the phenotype of NAD‐IDH mutations is confined to the eye.

Cytosolic NADP-isocitrate dehydrogenase of pea plants: Genomic clone characterization and functional analysis under abiotic stress conditions

NADPH is an essential electron donor in numerous biosynthetic and detoxification reactions. In animal, yeast and bacteria, the NADP-dependent isocitrate dehydrogenase (NADP-ICDH), which catalyzes the production of NADPH, is being recognized as an essential component of the antioxidative defence mechanisms. In plant cells, there is little information on the antioxidant properties of NADP-ICDH. Using a pea cDNA λgt11 library, the full-length cDNA of a NADP-ICDH was obtained. In pea leaves, the analyses of activity, protein and transcript expression of NADP-ICDH under six different abiotic stress conditions (CL, continuous light, HLI, high light intensity, D, continuous dark, LT, low-temperature HT, high-temperature and W, mechanical wounding) revealed a differential regulation at transcriptional and post-translational level depending on the abiotic stress. The activity and protein expression of NADP-ICDH and catalase increased only under HLI but the NADP-ICDH transcripts were up-regulated by cold stress (70%) and W (40%). Under the same conditions, the transcript analysis of glutathione reductase (GR), monodehydroascorbate reductase (MDAR) and ascorbate peroxidase (APX), key components of the antioxidative ascorbate–glutathione cycle, showed similar inductions. These data indicate that in pea plants the cytosolic NADP-ICDH shows a differential response, at mRNA and activity level, depending on the type of abiotic stress and suggests that this dehydrogenase could have a protective antioxidant role against certain environmental stresses in plants.

Oxidative inactivation of reduced NADP-generating enzymes in E. coli: iron-dependent inactivation with affinity cleavage of NADP-isocitrate dehydrogenase

Treatment of E. coli extract with iron/ascorbate preferentially inactivated NADP-isocitrate dehydrogenase without affecting glucose-6-phosphate dehydrogenase. NADP-Isocitrate dehydrogenase required divalent metals such as Mg(2+), Mn(2+ )or Fe(2+) ion. Iron/ascorbate-dependent inactivation of the enzyme was accompanied with the protein fragmentation as judged by SDS-PAGE. Catalase protecting the enzyme from the inactivation suggests that hydroxyl radical is responsible for the inactivation with fragmentation. TOF-MS analysis showed that molecular masses of the enzyme fragments were 36 and 12, and 33 and 14 kDa as minor components. Based on the amino acid sequence analyses of the fragments, cleavage sites of the enzyme were identified as Asp307-Tyr308 and Ala282-Asp283, which are presumed to be the metal-binding sites. Ferrous ion bound to the metal-binding sites of the E. coli NADP-isocitrate dehydrogenase may generate superoxide radical that forms hydrogen peroxide and further hydroxyl radical, causing inactivation with peptide cleavage of the enzyme. Oxidative inactivation of NADP-isocitrate dehydrogenase without affecting glucose 6-phosphate dehydrogenase shows only a little influence on the antioxidant activity supplying NADPH for glutathione regeneration, but may facilitate flux through the glyoxylate bypass as the biosynthetic pathway with the inhibition of the citric acid cycle under aerobic growth conditions of E. coli.