Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.1.1.49 (glucose-6-phosphate dehydrogenase)
 7,794 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of methotrexate and azathioprine, two drugs used in antipsoriatic therapy, on oxygen consumption of surviving human skin and on enzymatic activities of human skin homogenates were investigated. In concentrations of 1 mM/1, both substances provoked a significant decrease in oxygen consumption of human skin; in this respect, there was practically no difference between methotrexate and azathioprine. In the enzyme assays, however, azathioprine was, by far, less effective than methotrexate. After an incubation of 120 min azathioprine (1mM/1) inhibited lactate and glucose-6-phosphate dehydrogenase activities by about 10 per cent only, whereas the corresponding values with methotrexate amounted to 80 and 70 per cent, respectively. Methotrexate revealed an immediate inhibitory effect on pure glucose-6-phosphate dehydrogenase whereas azathioprine produced no changes in this mode. Furthermore, only methotrexate inhibited "acid" phosphatase activity of human skin homogenates.--These data sustain the theory that the better clinical efficacy of methotrexate in patients with psoriasis might be due to the more pronounced inhibition of important enzymes such as the enzymes of the pentose phosphate shunt.
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PMID:In vitro evaluation of methotrexate and azathioprine for antipsoriatic activity. 119 Aug 31

This paper presents the effects of combined exposure (noise, dust, nitrogen oxides) on the health condition of industrial workers, with special regard to red blood cell metabolism. 208 male industrial plant workers of the average age of 38.5 +/- 8.27 years and the average work period of 14.7 +/- 8.22 years were examined. The statistically significant increase of methemoglobin level was detected as well as some changes in erythrocyte metabolism in terms of increased activity of glucose-6-phosphate dehydrogenase, pyruvate kinase and in vitro production of lactic acid in erythrocytes. The observed changes indicate the influence of exposure to nitrogen oxides and the resulting cellular adaptation to unfavourable working conditions (activation of the pentose cycle and of the final stage of anaerobic glycolysis cycle).
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PMID:[Effect of combined exposure (noise, dust, nitrogen oxides) on health status of metal workers in heavy industry. Evaluation of erythrocyte metabolism]. 129 76

In the present study we examined renal proximal tubule glucose metabolism in the X-linked hypophosphatemic (Hyp/Y) mouse. Compared to those in its normal (+/Y) littermate, Hyp/Y mouse proximal tubules showed a higher rate of glucose production when using glutamine or alpha-ketoglutarate as a substrate. The glucose production rate was not, however, different when using malate or fructose as the substrate. PTH stimulated glucose production in +/Y, but not Hyp/Y, mouse proximal tubules. The PTH resistance in Hyp/Y mouse involves steps at and post-cAMP formation, because in Hyp/Y mouse proximal tubules PTH effects a lesser stimulation of cAMP generation, and addition of 8-bromo-cAMP failed to increase the glucose production rate. The rate of glucose utilization as a whole was not different in the two groups, but the rate of glucose metabolized through the pentose cycle (PC) pathway was markedly lower in Hyp/Y mouse proximal tubules. The lower PC activity in Hyp/Y mouse proximal tubules did not result from a defect of PC enzymes, because both glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase enzyme activities were intact, and phenazine methosulfate was able to stimulate PC activity. The higher rate of glucose production and the lower rate of PC activities persisted in the in vitro cultured Hyp/Y mouse proximal tubular cells. These results suggest that the altered glucose metabolism in the Hyp/Y mouse proximal tubule is not maintained by external influences and may be an abnormality intrinsic to these cells.
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PMID:Altered proximal tubule glucose metabolism in X-linked hypophosphatemic mice. 130 37

Male outbred Sprague-Dawley rats were fed a choline-deficient diet containing 0.10% DL-ethionine (CDE) for 4, 6, 10, 14 or 22 weeks followed by a standard diet for up to 59 weeks. Liver sections were histochemically analyzed for the following parameters: basophilia, glycogen content and the activities of glycogen synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6PASE), glucose-6-phosphate dehydrogenase (G6PDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), glycerin-3-phosphate dehydrogenase (G3PDH), 'malic enzyme' (MDH), alkaline phosphatase (ALKPASE) and gamma-glutamyltranspeptidase (GGT). The stop experiments revealed that many of the oval cells proliferating during the first 4-6 weeks may undergo necrotic changes and disappear with time, whereas cholangiofibroses appearing in animals fed CDE for at least 10 weeks are persistent lesions. The sequence of lesions seen in this study, leading from persistent oval cells through cholangiofibroses to cholangiofibromas, strongly suggests that the oval cells are the precursor cells of cholangiocellular tumors. The proliferating oval cells and the hepatic foci consisting of clear and acidophilic or mixed cell populations were always spatially separated and no transitions between oval and parenchymal cells were observed. These results argue against a precursor-product relationship between oval and parenchymal cells. Both proliferating and persistent oval cells, cholangiofibroses and cholangiofibromas showed a strong staining for G6PDH, GAPDH, G3PDH, MDH, ALKPASE and GGT; low PHO, SYN and G6PASE activities were also detected in these lesions. Persistent glycogen-storage foci, which developed in all rats fed CDE for 4-14 weeks followed by a normal lab chow for over a year, had increased PHO, G6PDH, MDH, ALKPASE and GGT activities, while SYN, GAPDH and G3PDH activities remained unaltered and G6PASE activity decreased. Mixed cell foci appearing in animals fed CDE for 22 weeks followed by a normal lab chow for 59 weeks had strongly increased G6PDH, GAPDH, G3PDH, MDH, ALKPASE and GGT activities as well as decreased G6PASE activity. These results indicate that the characteristic metabolic pattern of preneoplastic hepatic foci is independent of the further administration of the carcinogenic diet. The shift from glycogen metabolism to glycolysis and the pentose phosphate pathway occurring during the later stages of CDE-induced hepatocarcinogenesis is an autogenous process apparently directing the disturbed carbohydrate metabolism towards alternative metabolic pathways. A similar metabolic shift also seems to take place during cholangiocarcinogenesis.
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PMID:Persistence of the cholangiocellular and hepatocellular lesions observed in rats fed a choline-deficient/DL-ethionine-supplemented diet. 131 Sep 7

Human spermatozoa contain appreciable amounts of intracellular glutathione, which has a protective function against peroxidative degradation of spermatozoal polyunsaturated fatty acids by the NADPH-dependent glutathione peroxidase/reductase enzymatic system. The glutathione system provides a basic defense against peroxidative damage, without which the superoxide dismutase system would dominate. Since oxidative damage is said to include enzyme leakage and changes in metabolism, cytochrome oxidase and lactate dehydrogenase activities were used as indicators of the energy metabolism in unwashed and washed human spermatozoa during lipid peroxidation. Lipid peroxidation was induced by aerobic incubation of sperms in the presence of sodium ascorbate and ferrous sulphate. In addition, since NADPH concentrations influence the concentration of reduced glutathione, we studied glucose-6-phosphate dehydrogenase activity as an indicator of pentose phosphate shunt activity, the main source of NADPH. Microdensitometric measurements of the three enzymes were made by a Vickers M85a scanning microdensitometer. We found that the lipid peroxidation process greatly affects the 3 enzymatic activities examined and that seminal plasma protects against the extensive deleterious effects of lipid peroxidation.
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PMID:Cytophotometric assay of cytochrome oxidase, lactate dehydrogenase and glucose-6-phosphate dehydrogenase activities in human peroxidized spermatozoa. 133 42

To examine whether stimulation of alpha-adrenergic receptors may affect the oxidative pentose phosphate pathway (PPP) in the rat heart, norepinephrine (NE) and the alpha-adrenergic agonist norfenephrine were used. NE was administered as a continuous intravenous infusion in awake rats for 3 days. It stimulated the activity of cardiac glucose-6-phosphate dehydrogenase (G-6-PD), the first and regulating enzyme of the oxidative PPP, in a dose-dependent manner. With the highest dose (0.2 mg.kg-1.hr-1), there was also a time-dependent enhancement. The increase observed after 48 hours was attenuated partially by the beta-receptor blocker metoprolol and the alpha-receptor blocker prazosin. It was entirely abolished when both drugs were administered. Carvedilol, a beta-adrenergic blocker and vasodilator with alpha 1-blocking activity (0.5 mg.kg-1.hr-1), prevented the NE-induced increase in cardiac G-6-PD activity, in functional parameters (heart rate, left ventricular systolic pressure, and left ventricular dP/dtmax), and in the heart weight/body weight ratio. The alpha-adrenergic stimulator norfenephrine increased myocardial G-6-PD activity; prazosin prevented this stimulation. NE and norfenephrine also elevated the available pool of cardiac 5-phosphoribosyl-1-pyrophosphate. G-6-PD activity was enhanced in cardiac myocytes freshly isolated from the left ventricle of rats that had received NE infusion for 3 days (12.3 +/- 1.4 units/g protein) compared with control rats (1.5 +/- 0.4 units/g protein). The activity of 6-phosphogluconate dehydrogenase, one of the enzymes in the oxidative PPP, was elevated only moderately from 12.7 +/- 0.7 to 19.1 +/- 1.4 units/g protein. Combined alpha- and beta-receptor blockade with carvedilol attenuated these effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of norepinephrine on the oxidative pentose phosphate pathway in the rat heart. 137 61

The capacity of the oxidative pentose phosphate pathway (PPP) in the heart is small, since the activity of glucose-6-phosphate dehydrogenase (G-6-PD), the first and rate-limiting enzyme, is very low. Basically, two mechanisms are involved in the regulation of this pathway. Under normal conditions, G-6-PD is inhibited by NADPH. This can immediately be overcome in the isolated perfused rat heart by increasing the oxidized glutathione and by elevating the NADP+/NADPH ratio. Apart from this rapid control mechanism, there exists a long-term regulation which involves the synthesis of G-6-PD. All catecholamines that were administered stimulated the activity of myocardial G-6-PD in a time- and dose-dependent manner. This stimulation was due to increased new synthesis of enzyme protein, since the G-6-PDmRNA was specifically enhanced. As a consequence of the stimulation of the oxidative PPP, the available pool of 5-phosphoribosyl-1-pyrophosphate (PRPP) was elevated which serves as an important precursor substrate for purine and pyrimidine nucleotide synthesis. The limiting step in the oxidative PPP can be bypassed by ribose which leads to an elevation of the cardiac PRPP pool. The decline in the ATP that is induced in many pathophysiological conditions can be attenuated or even entirely prevented by i.v. infusion of ribose. In some experimental in vivo rat models such as in the overloaded and catecholamine-stimulated heart and in the non-ischemic region of the infarcted heart, the normalization of the metabolic situation was accompanied by an improvement of global heart function. Ribose application has been shown to be beneficial in several clinical disease states such as myoadenylate deaminase deficiency and McArdle's disease. Moreover, ribose facilitated thallium-201 redistribution and markedly improved the detection of reversible ischemic injury of the pig and human heart.
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PMID:The oxidative pentose phosphate pathway in the heart: regulation, physiological significance, and clinical implications. 138 63

We have studied the effects of triiodothyronine (T3) on heart function, on the myocardial oxidative pentose phosphate pathway, and on heart weight in spontaneously hypertensive (SHR) rats. Another aim was to examine whether these T3-effects may be reversible. T3 was administered daily (0.2 mg/kg s.c.) for 14 days. Compared to the untreated SHR controls, T3 induced an increase in heart rate (beats/min) from 357 +/- 10 (n = 17) to 553 +/- 10 (n = 17), in the pressure-rate-product (mm Hg/min) from 78 400 +/- 4500 (n = 15) to 113 700 +/- 4800 (n = 15), and in the heart weight/body weight ratio (mg/g) from 4.2 +/- 0.2 (n = 20) to 5.8 +/- 0.2 (n = 19). The activity of myocardial glucose-6-phosphate dehydrogenase, the first and rate-limiting enzyme of the oxidative pentose phosphate pathway (units/g protein), was elevated from 4.2 +/- 0.2 (n = 9) to 7.0 +/- 0.6 (n = 9) after 14 days of T3-treatment, while the activity of 6-phosphogluconate dehydrogenase, one of the following enzymes in the pathway, was not altered appreciably. These changes returned to the respective control values when T3-treatment was discontinued for 14 days. Our results demonstrate that T3 had a positive chronotropic effect and induced an additional heart enlargement in an animal model with already established cardiac hyperfunction and hypertrophy. The effects on heart function and weight, which were fully reversible, were not as pronounced as in normal Sprague-Dawley rats.
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PMID:Effects of triiodothyronine in spontaneously hypertensive rats. Studies on cardiac metabolism, function, and heart weight. 141 3

The mass concentrations of whole blood reduced glutathione and catalytic activity concentrations of the enzymes, glucose-6-phosphate dehydrogenase (EC 1.1.1.49), glutathione reductase (EC 1.6.4.2) and glutathione peroxidase (EC 1.11.9) were analysed in 25 cases of homozygous beta-thalassaemia, 20 cases of heterozygous beta-thalassaemia and 10 controls. The results showed a significant elevation of reduced glutathione and enzymes of the pentose phosphate pathway in homozygous beta-thalassaemia, indicating the existence of an enzyme-regulated glutathione turnover system in the overt state to combat the augmented red cell membrane damage due to auto-oxidant threat. However, in heterozygous beta-thalassaemia, reduced glutathione was increased, but there was no similar elevation of enzymes except for glutathione peroxidase.
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PMID:Enzymes of the pentose phosphate pathway in glutathione-regulated membrane protection in beta-thalassaemia. 144 62

Demonstrating that naturally occurring enzyme polymorphisms significantly impact metabolic pathway flux is a fundamental step in examining the possible adaptive significance of such polymorphisms. In earlier studies of the glucose-6-phosphate dehydrogenase (G6PD) polymorphism in Drosophila melanogaster, we used two different methods, exploiting both genotype-dependent interactions with the 6Pgd locus, and conventional steady-state kinetics to examine activity differences between the two common allozymes. In this report we use 1-14C- and 6-14C-labeled glucose to estimate directly genotype-dependent flux differences through the pentose shunt. Our results show that G6pdA genotype possesses statistically lower pentose shunt flux than G6pdB at 25 degrees. We estimate this to be about a 32% reduction, which is consistent with the two former studies. These results reflect a significant responsiveness of pentose shunt flux to activity variation at the G6PD-catalyzed step, and predict that the G6PD allozymes generate a polymorphism for pentose shunt flux.
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PMID:Direct measurement of in vivo flux differences between electrophoretic variants of G6PD from Drosophila melanogaster. 146 30


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