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malfunction
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C57BL/6J mice, which have a deletion in the Nnt gene, exhibit greater resistance to acute pulmonary infection with Streptococcus pneumoniae. Macrophages from these mice generate more reactive oxygen species and establish a stronger inflammatory response to this pathogen
malfunction
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knockdown of the enzyme inhibits the contribution of glutamine to the tricarbonic acid cycle and activates glucose catabolism in SkMel5 melanoma cells. The increase in glucose oxidation partially occurs through pyruvate carboxylase and renders NNT knockdown cells more sensitive to glucose deprivation. Importantly, knocking down NNT inhibits reductive carboxylation in SkMel5 and 786-O renal carcinoma cells. Overexpression of NNT is sufficient to stimulate glutamine oxidation and reductive carboxylation, whereas it inhibits glucose catabolism in the TCA cycle, with impairment of the NAD(P)H/NAD(P)+ ratios
malfunction
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small interfering RNA silencing of the enzyme in PC-12 cells results in decreased cellular NADPH levels, altered redox status of the cell in terms of decreased GSH/GSSG ratios and increased H2O2 levels, thus leading to an increased redox potential (a more oxidized redox state). NNT knockdown results in a decrease of oxidative phosphorylation while anaerobic glycolysis levels remain unchanged. Decreased oxidative phosphorylation was associated with 1. inhibition of mitochondrial pyruvate dehydrogenase and succinyl-CoA:3-oxoacid CoA transferase activity, 2. reduction of NADH availability, 3. decline of mitochondrial membrane potential, and 4. decrease of ATP levels
malfunction
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spontaneous C57BL/6J(B6J-NntMUT) mutant mice show major redox alterations in respiring mitchondria, including an absence of transhydrogenation between NAD+ and NADP+, higher rates of H2O2 release, the spontaneous oxidation of NADPH,the poor ability to metabolize organic peroxide, and a higher susceptibility to undergo Ca2+-induced mitochondrial permeability transition. Liver mitochondria from B6J-NntMUT mice do not possess NNT activity. The mitochondria of mutant B6J-NntMUT mice exhibit increased oxidized/reduced glutathione ratios as compared to wild-type B6JUnib-NntW mice, phenotypes, overview
malfunction
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enzyme inhibition decreases NADPH levels, decreases thioredoxin and thioredoxin reductase activity, and increases toxicity to oxidative stress
malfunction
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enzyme knockdown decreases reductive carboxylation and stimulates glucose catabolism in the tricarboxylic acid cycle
malfunction
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gene disruption of pntA results in phenotypic growth defects observed under low light intensities in the presence of glucose, whereas under autotrophic conditions the mutant does not differ from the wild type strain
malfunction
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lack of enzyme activity impairs peroxide metabolism in intact mitochondria
malfunction
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the absence of enzyme leads to variation in mitochondrial function and contributes to a unique mitochondrial redox phenotype that influences susceptibility to hypertension by contributing to endothelial and vascular dysfunction
malfunction
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spontaneous C57BL/6J(B6J-NntMUT) mutant mice show major redox alterations in respiring mitchondria, including an absence of transhydrogenation between NAD+ and NADP+, higher rates of H2O2 release, the spontaneous oxidation of NADPH,the poor ability to metabolize organic peroxide, and a higher susceptibility to undergo Ca2+-induced mitochondrial permeability transition. Liver mitochondria from B6J-NntMUT mice do not possess NNT activity. The mitochondria of mutant B6J-NntMUT mice exhibit increased oxidized/reduced glutathione ratios as compared to wild-type B6JUnib-NntW mice, phenotypes, overview
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malfunction
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knockdown of the enzyme inhibits the contribution of glutamine to the tricarbonic acid cycle and activates glucose catabolism in SkMel5 melanoma cells. The increase in glucose oxidation partially occurs through pyruvate carboxylase and renders NNT knockdown cells more sensitive to glucose deprivation. Importantly, knocking down NNT inhibits reductive carboxylation in SkMel5 and 786-O renal carcinoma cells. Overexpression of NNT is sufficient to stimulate glutamine oxidation and reductive carboxylation, whereas it inhibits glucose catabolism in the TCA cycle, with impairment of the NAD(P)H/NAD(P)+ ratios
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malfunction
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the absence of enzyme leads to variation in mitochondrial function and contributes to a unique mitochondrial redox phenotype that influences susceptibility to hypertension by contributing to endothelial and vascular dysfunction
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malfunction
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C57BL/6J mice, which have a deletion in the Nnt gene, exhibit greater resistance to acute pulmonary infection with Streptococcus pneumoniae. Macrophages from these mice generate more reactive oxygen species and establish a stronger inflammatory response to this pathogen
-
malfunction
-
C57BL/6J mice, which have a deletion in the Nnt gene, exhibit greater resistance to acute pulmonary infection with Streptococcus pneumoniae. Macrophages from these mice generate more reactive oxygen species and establish a stronger inflammatory response to this pathogen
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metabolism
the enzyme uses energy from the mitochondrial proton gradient to produce high concentrations of NADPH
metabolism
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the enzyme coordinates glutamine and glucose metabolism in the tricarboxylic acid cycle
physiological function
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crucial role of the enzyme in the maintenance of the redox environment. The proton gradient across the mitochondrial inner membrane strongly stimulates the forward reaction, i.e., the generation of NADPH. Under anaerobic and energy-deficient conditions, the reverse reaction catalyzed by NNT, i.e., the generation of NADH, also has transient effects on maintaining mitochondrial membrane potential through NADPH hydrolysis and H+ pumping, but the contribution of the backward reaction to the proton gradient is probably of little significance under physiological conditions. Oxidized cellular redox state is linked to a decline in cellular bioenergetics, overview
physiological function
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mitochondrial transhydrogenation serves as a source for this NADPH. It plays a key role in larvalpupal development
physiological function
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nicotinamide nucleotide transhydrogenase is a mitochondrial enzyme that transfers reducing equivalents from NADH to NADPH
physiological function
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nicotinamide nucleotide transhydrogenase, NNT, is a nuclear-encoded protein that functions as a redox-driven proton pump catalyzing the reversible reduction of NADP+ by NADH and conversion of NADH to NAD+. The enzyme acts as a modulator of macrophage inflammatory responses. The enzyme NNT is an efficient generator of NADPH required by glutathione reductase to reduce glutathione, a component necessary to decrease the buildup of reactive oxygen species
physiological function
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the enzyme functions as a high-capacity source of mitochondrial NADPH and that its functional loss due to the Nnt mutation results in mitochondrial redox abnormalities, most notably a poor ability to sustain NADP+ and glutathione in the reduced states. The enzyme is assembled across the inner mitochondrial membrane and translocates H+ to the mitochondrial matrix as NADP+ is reduced at the expense of NADH on the matrix side. The electrochemical gradient across the inner mitochondrial membrane shifts the NNT equilibrium to the right
physiological function
the enzyme plays a role in reactive oxygen species detoxification in human adrenal glands
physiological function
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the enzyme activity impacts mitochondrial redox balance and the development of hypertension in mice
physiological function
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the enzyme activity in Synechocystis is directly linked to mixotrophic growth, implicating that under these conditions the enzyme functions to balance the NADH:NADPH equilibrium specifically in the direction of NADPH
physiological function
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the enzyme links mitochondrial respiration and antioxidant activity in brain mitochondria
physiological function
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the enzyme functions as a high-capacity source of mitochondrial NADPH and that its functional loss due to the Nnt mutation results in mitochondrial redox abnormalities, most notably a poor ability to sustain NADP+ and glutathione in the reduced states. The enzyme is assembled across the inner mitochondrial membrane and translocates H+ to the mitochondrial matrix as NADP+ is reduced at the expense of NADH on the matrix side. The electrochemical gradient across the inner mitochondrial membrane shifts the NNT equilibrium to the right
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physiological function
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nicotinamide nucleotide transhydrogenase is a mitochondrial enzyme that transfers reducing equivalents from NADH to NADPH
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physiological function
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the enzyme activity impacts mitochondrial redox balance and the development of hypertension in mice
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physiological function
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nicotinamide nucleotide transhydrogenase, NNT, is a nuclear-encoded protein that functions as a redox-driven proton pump catalyzing the reversible reduction of NADP+ by NADH and conversion of NADH to NAD+. The enzyme acts as a modulator of macrophage inflammatory responses. The enzyme NNT is an efficient generator of NADPH required by glutathione reductase to reduce glutathione, a component necessary to decrease the buildup of reactive oxygen species
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physiological function
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nicotinamide nucleotide transhydrogenase, NNT, is a nuclear-encoded protein that functions as a redox-driven proton pump catalyzing the reversible reduction of NADP+ by NADH and conversion of NADH to NAD+. The enzyme acts as a modulator of macrophage inflammatory responses. The enzyme NNT is an efficient generator of NADPH required by glutathione reductase to reduce glutathione, a component necessary to decrease the buildup of reactive oxygen species
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