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

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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)

Parietal cells in the luminal segments of mouse gastric glands show high activity of acid-secreting potassium-dependent adenosine triphosphatase (H+, K+-ATPase) and of nicotinamide adenine dinucleotide-linked isocitrate dehydrogenase (NAD-ICDHase) and malate dehydrogenase (MDHase) but low activity of succinate dehydrogenase (SDHase). This pattern of activity is reversed in the basal segments of the same glands. These results and previous morphological findings support the conclusion that luminal segment parietal cells are much more active in hydrochloric acid secretion than those of the basal segment. The origin of this zonation may be either cellular deterioration with age or some more specific form of regulation of parietal cell metabolism.
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PMID:Cytochemical evidence for functional zonation of parietal cells within the gastric glands of the mouse. 631 15

The metabolic characteristics of 12 skeletal muscles of the sheep were studied. Glycolytic activities (hexokinase, glycogen synthetase I and D, phosphorylase a and b, phosphofructokinase) were measured. Myofibrillar ATPase activity was evaluated. Oxygen consumption, respiratory control and carnitine palmityl transferase, isocitrate dehydrogenase, succinate dehydrogenase and cytochrome oxidase activities were measured in isolated mitochondria. Three metabolic types could be distinguished; (1) essentially oxidative slow twitch muscles, typified by the supraspinatus and infraspinatus, having low ATPase activity, (2) fast twitch red muscles, typified by the longissimus dorsi and the semimembranosus, having a higher ATPase activity and both high oxidative and high glycolytic activity, and (3) essentially glycolytic fast twitch muscles, typified by the tensor fascia lata and the semitendinosus, having the highest ATPase activity.
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PMID:Metabolic types of muscle in the sheep: I. Myosin ATPase, glycolytic, and mitochondrial enzyme activities. 645 90

A mathematical model is proposed to describe the interaction between glycolysis, the Krebs cycle and 3-oxidation (beta OX). The model incorporates the activations of phosphofructokinase by AMP and of isocitrate dehydrogenase by ADP as well as the inhibitions of citrate synthase by citrate, of acyl CoA synthase by excess CoAsAcyl, of pyruvate dehydrogenase (PDH) and the beta OX helix by the products CoAsAc and NADH. These regulations have been shown to provide consecutive triggering of the fatty acid and glucose oxidation systems with an increase in the ATPase load, the beta OX of fatty acids being a major source of energy at small loads. The steady state rates of glycolysis and PDH-reaction begin to increase at larger loads when the rate of beta OX is close to its maximum value. At maximum ATPase loads, the glucose oxidation accounts for more than 80% of the total energy production. Under limited fatty acid supply, the transfer to glucose oxidation gives rise to a region of the ATPase loads, where in the steady state levels of NADH and CoAsAc increase with load.
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PMID:[Ratio between carbohydrate and lipid metabolism in muscle cell energy metabolism during ATPase loading. Mathematical model]. 645 74

The influence on chick myogenesis of hypothyroid status induced in ovo by methimazole was histologically (number and types of muscle fibers) and biochemically studied. A single injection of methimazole induced an hypothyroid status during embryogenesis, as shown by the plasma T4 levels which were separately assayed in male and female controls and treated embryos from day 12 of incubation to day 4 after hatching. In both sexes, control plasma T4 reached a peak on day 20 of incubation, but the female values were significantly higher; plasma T4 in the treated embryos remained at a low level independently of sex. Only methimazole-treated males showed a significant increase (P less than 0.01) in the total number of fibers of the two muscles (tibialis posterior and flexor digitorum) studied. Moreover, the histochemical results on succinate dehydrogenase and myofibrillar ATPase evidenced that, of the three fiber types (alpha R, alpha W and beta R) constituting the skeletal muscles, only the alpha fibers increased significantly. Aldolase (glycolytic) and NADP isocitrate dehydrogenase (tricarboxylic acid cycle) activities, measured on the adductor and pectoralis muscles, showed a similar developmental pattern in control and treated animals, but was retarded in the latter due to a 5-day delay in hatching. It is not known whether the tissular differences were related directly to the hypothyroid status, to alterations in nervous system differentiation or, as suggested by intersexual differences, to modifications in hormonal balance.
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PMID:Influence of experimental hypothyroidism on chick myogenesis. 734 20

The effect of DL alpha-lipoic acid on the nephrotoxic potential of gentamicin was examined. Intraperitoneal injection of gentamicin (100 mg/kg/day) to rats resulted in decreased activity of the glycolytic enzymes-hexokinase, phosphoglucoisomerase, aldolase and lactate dehydrogenase. The two gluconeogenic enzymes--glucose-6-phosphatase and fructose-1,6-diphosphatase, the transmembrane enzymes namely the Na+, K(+)-ATPase, Ca(2+)-ATPase, Mg(2+)-ATPase and the brushborder enzyme alkaline phosphatase, also showed decreased activities. This decrease in the activities of ATPases and alkaline phosphatase suggests basolateral and brush border membrane damage. Decreased activity of the TCA cycle enzymes isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH) and malate dehydrogenase (MDH), suggests a loss in mitochondrial integrity. These biochemical disturbances were effectively counteracted by lipoic acid administration. Lipoic acid administration by gastric intubation at two different concentrations (10 mg and 25 mg/kg/day) brought about an increase in the activity of the glycolytic enzymes, ATPases and the TCA cycle enzymes. The gluconeogenic enzymes however showed a further decrease in their activities at both the concentrations of lipoic acid administered. These observations shed light on the nephroprotective action of lipoic acid against experimental aminoglycoside toxicity and the protection afforded at 25 mg/kg/day of lipoic acid was noted to be higher than that at 10 mg level.
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PMID:Role of DL alpha-lipoic acid in gentamicin induced nephrotoxicity. 765 73

Oxidative stress is associated with the formation of oxidized glutathione (GSSG) in the cells, which can form mixed disulfide with proteins leading to alteration of their function. The present study looks at the effect of in vitro exposure of GSSG on intestinal mitochondria and brush border membrane (BBM). Incubation with 1 mM GSSG increased the protein bound GSH in mitochondria by 15-fold. This was associated with loss of activity of certain mitochondrial enzymes such as succinic dehydrogenase, isocitrate dehydrogenase, total ATPase and NADH dehydrogenase whereas NADH oxidase was not affected. A similar treatment of BBMV with GSSG increased the protein bound GSH by 4.7-fold without altering its enzyme activity. Exposure to GSSG had no effect on the Na(+)-dependent glucose transport by BBMV. These studies suggest that GSSG formed during oxidative stress may modify thiol groups in proteins by forming mixed disulfides leading to functional alteration of certain cellular proteins.
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PMID:Effect of oxidized glutathione on intestinal mitochondria and brush border membrane. 767 Nov 37

Chaperonin 60 and chaperonin 10 (GroEL and GroES homologues, respectively) have been isolated from extracts of the anaerobic thermophile Thermoanaerobacter brockii. A simple and rapid purification for chaperonin 60 made use of hydrophobic and anion-exchange chromatographies, and could be readily scaled up; approximately 2 mg pure chaperonin 60 was obtained/g cells. In contrast with all other prokaryotic chaperonin 60 proteins that have been studied, which are tetradecamers, including those from Thermus sp., the T. brockii protein is a heptamer, and as isolated was not in association with chaperonin 10. The preparation is readily crystallized using 2-propanol or poly(ethylene glycol) with MgCl2. The N-terminal amino acid sequence of this preparation is similar to other thermophilic chaperonin 60 proteins. Chaperonin 10 was purified from the flow-through of the first hydrophobic column (which bound chaperonin 60) using a more hydrophobic adsorbent to remove contaminating proteins, followed by anion-exchange chromatography. Chaperonin 10 was obtained with a yield of approximately 10% that of chaperonin 60. The subunit molecular mass of chaperonin 10 determined by electrospray mass spectrometry is 10254 +/- 0.4 Da, which is very similar to the molecular mass of Escherichia coli GroES. Similarly, the subunit size of chaperonin 60 determined by mass spectrometry is very similar to that of GroEL, at 57949 +/- 10 Da. T. brockii chaperonin 60 has an ATPase activity that is suppressed by chaperonin 10, and the two proteins together are active in protein-folding assays. Mitochondrial malate dehydrogenase was successfully refolded at 37 degrees C after denaturation in guanidine hydrochloride, using T. brockii chaperonin 60 and chaperonin 10, or chaperonin 60 and E. coli GroES. The denatured enzyme was protected from aggregation by association with chaperonin 60. Guanidine-hydrochloride-denatured preparations of isocitrate dehydrogenase and secondary alcohol dehydrogenase isolated from T. brockii were also refolded at 60-65 degrees C. In each case, refolding required chaperonin 60, chaperonin 10 and ATP, giving up to 80% regeneration of control activity.
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PMID:Purification and characterization of chaperonin 60 and chaperonin 10 from the anaerobic thermophile Thermoanaerobacter brockii. 791 71

The pregnant rats were treated with formaldehyde (0.5 mg/kg daily per os) during whole period of pregnancy. The activity of cytochrome-c-oxidase, malate dehydrogenase, nucleotidase, glucose-6-phosphatase, beta-glucuronidase, N-acetyl-beta-glucosaminidase, beta-galactosidase, H(+)-ATPase, glutamate dehydrogenase, NAD- and NADP-isocitrate dehydrogenase, fructose-bisphosphate aldolase, glucose-6-phosphate dehydrogenase and content of protein in liver celts of offsprings (newborns, 2 weeks age and 2 months age) were studied. It was shown differences in development enzyme systems of control and experimental animals during ontogenesis.
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PMID:[Experimental study of the effect of formaldehyde during embryogenesis on the activity of rat liver enzyme systems in ontogenesis]. 913 53

This paper reviews the model of the control of mitochondrial substrate oxidation by Ca2+ ions. The mechanism is the activation by Ca2+ of four mitochondrial dehydrogenases, viz. glycerol 3-phosphate dehydrogenase, the pyruvate dehydrogenase multienzyme complex (PDH), NAD-linked isocitrate dehydrogenase (NAD-IDH) and 2-oxoglutarate dehydrogenase (OGDH). This results in the increase, or near-maintenance, of mitochondrial NADH/NAD ratios in the activated state, depending upon the tissue and the degree of 'downstream' activation by Ca2+, likely at the level of the F1Fo ATPase. Higher values of the redox span of the respiratory chain allow for greatly increased fluxes through oxidative phosphorylation with a minimal drop in protonmotive force and phosphorylation potential. As PDH, NAD-IDH and OGDH are all located within the inner mitochondrial membrane, it is changes in matrix free Ca2+ [Ca2+]m which act as a signal to these activities. In this article, we review recent work in which [Ca2+]m is measured in cells and tissues, using different techniques, with special emphasis on the question of the degree of damping of [Ca2+]m relative to changes in cytosol free Ca2+ in cells with rapid transients in cytosol Ca2+, e.g. cardiac myocytes. Further, we put forward the point of view that the failure of mitochondrial energy transduction to keep pace with cellular energy needs in some forms of heart failure may involve a failure of [Ca2+]m to be raised adequately to allow the activation of the dehydrogenases. We present new data to show that this is so in cardiac myocytes isolated from animals suffering from chronic, streptozocin-induced diabetes. This raises the possibility of therapy based upon partial inhibition of mitochondrial Ca2+ efflux pathways, thereby raising [Ca2+]m at a given, time-average value of cytosol free Ca+2.
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PMID:Role of mitochondrial calcium transport in the control of substrate oxidation. 974 30

Oxidative damage, through increased production of free radicals, is believed to be involved in UV-induced cataractogenesis (eye lens opacification). The possibility of UVB radiation causing damage to important lenticular enzymes was assessed by irradiating 3 months old rat lenses (in RPMI-1640 medium) at 300 nm (100 microWcm(-2)) for 24 h, in the absence and presence of ascorbic acid, alpha-tocopherol acetate and beta-carotene. UVB irradiation resulted in decreased activities of hexokinase, glucose-6-phosphate dehydrogenase, aldose reductase, and Na, K- ATPase by 42, 40, 44 and 57% respectively. While endopeptidase activity (229%) and lipid peroxidation (156%) were increased, isocitrate dehydrogenase activity was not altered on irradiation. In the presence of externally added ascorbic acid, tocopherol and beta-carotene (separately) to the medium, the changes in enzyme activities (except endopeptidase) and increased lipid peroxidation, due to UVB exposure, were prevented. These results suggest that UVB radiation exerts oxidative damage on lens enzymes and antioxidants were protective against this damage.
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PMID:Protection against UVB inactivation (in vitro) of rat lens enzymes by natural antioxidants. 1039 Nov 22


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