Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:EXPT02288 (NADH)
 21,914 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Citrate synthase activity of Saccharomyces cerevisiae was determined by a radioactive assay procedure and the reaction product, 14C-citric acid, was identified by chromatographic techniques. ATP, d-ATP, GTP and NADH were most inhibitory to the citrate synthase invitro. The activity was inhibited to a lesser extent by ADP, UTP, and NADP whereas, AMP and CTP were much less inhibitory. NADH, like NAD, glutamic acid, glutamine, arginine, ornithine, proline, aspartic acid and alpha-ketoglutarate exhibited no inhibition. These results have been discussed in the light of the role of citrate synthase for the energy metabolism and glutamic acid biosynthesis.
 ...
PMID:Regulation of citrate synthase activity of Saccharomyces cerevisiae. 0

Evidence is summarized indicating that mitochondrial respiration and citric acid cycle activity in the intact heart are controlled by the cytosolic phosphate potential and mitochondrial NAD oxidation-reduction state. Data are presented showing that the effect of respiratory acidosis is greater than that of metabolic acidosis in inhibiting left ventricular pressure development in the perfused rat heart, because of a greater fall of intracellular pH under the former conditions. Respiratory acidosis is shown to be readily associated with tissue hypoxia as a result of an increased vascular resistance and diminished flow rate through the coronary circulation. In nonischemic respiratory acidosis, the rate of ATP production is well balanced by the rate of ATP utilization, and tissue ATP and creatine-P levels remain approximately normal. Partially ischemic respiratory acidosis was associated with low tissue levels of ATP and creatine-P and high tissue levels of lactate and NADH. Ischemic areas with sharp border zones were visualized during and after an abrupt decrease of perfusion fluid pH by directly photographing NADH fluorescence from the surface of perfused hearts. Reversal of the hypodynamic state with partially ischemic respiratory acidosis could not be achieved by augmenting the coronary flow by means of an external pump. The demonstration of the existence of sharp zones of high pyridine nucleotide fluorescence adjacent to normal zones indicates a great heterogeneity of coronary perfusion and the existence of steep oxygen gradients in the intact heart.
 ...
PMID:Control of energy production in cardiac muscle: effects of ischemia in acidosis. 2 5

The contributions of NAD-specific and NADP-specific isocitrate dehydrogenases to isocitrate oxidation in isolated intact rat liver mitochondria were examined using DL-threo-alpha-methylisocitrate (3-hydroxy-1,2,3-butanetricarboxylate) to specifically inhibit flux through NADP-specific isocitrate dehydrogenase. Under a range of conditions tested with respiring mitochondria, the rate of isocitrate oxidation was decreased by about 20--40% by inhibition of NADP-isocitrate dehydrogenase, and matrix NADP became more oxidized. (a) For mitochondria incubated with externally added DL-isocitrate and citrate, the rate of isocitrate oxidation obtained by extrapolation to infinite alpha-methylisocitrate concentration was approximately 70% of the uninhibited rate in both state 3 and state 4. (b) With pyruvate plus malate added as substrates of citric acid cycle oxidation and isocitrate generated intramitochondrially, a concentration of alpha-methylisocitrate (400 microM) sufficient for 99.99% inhibition of NADP-isocitrate dehydrogenase inhibited isocitrate oxidation in states 4 and 3 by 21 +/- 6% and 19 +/- 11% (mean +/- SEM), respectively. (c) With externally added isocitrate and citrate, the addition of NH4Cl increased isocitrate oxidation by 3--4-fold, decreased NADPH levels by 30--40% and 2-oxoglutarate accumulation by about 40%. The further addition of 600 microM alpha-methylisocitrate decreased the NH4Cl-stimulated isocitrate oxidation by about 40% and decreased NADPH to about 30% of the level prevailing in the absence of NH4Cl; nevertheless, the rate of isocitrate oxidation was still twice as large in the presence of NH4Cl and alpha-methylisocitrate as in their absence. Experiments were also performed with intact mitochondria incubated with respiratory inhibitors to determine additional factors which might affect the flux through the two isocitrate dehydrogenases. (a) In the coupled reduction of acetoacetate by isocitrate, where the rate of reoxidation of reduced pyridine nucleotides is limited by NAD-specific 3-hydroxybutyrate dehydrogenase, 85--100% of the rate of 3-hydroxybutyrate formation was retained in the presence of 400--900 microM alpha-methylisocitrate. (b) In a system where the rate of isocitrate oxidation is limited by the rate of NADPH reoxidation by glutathione reductase, the rate of glutathione reduction extrapolated to infinite alpha-methylisocitrate concentration was from 20--40% of the uninhibited rate. (c) In the coupled synthesis of glutamate from isocitrate and NH4Cl, where the reoxidation of NADPH and NADH can occur via glutamate dehydrogenase, the rate of glutamate production extrapolated to infinite alpha-methylisocitrate concentration was about 60% of the uninhibited rate.
 ...
PMID:Activities of NAD-specific and NADP-specific isocitrate dehydrogenases in rat-liver mitochondria. Studies with D-threo-alpha-methylisocitrate. 3 61

Young mycelia of the fungus Neurospora crassa contain a soluble NADH-linked sideramine reductase, which may be responsible for liberating iron in vivo from accumulated sideramines during iron-deficient cultivation. The enzymes can be assayed using a soluble supernatant fraction, EDTA, and an atmosphere of pure nitrogen. The enzyme is stable without loss of activity up to 45 degrees C and has an optimum of activity at pH 7.0. Besides coprogen (Km = 100 micrometer, V=2.8 nmol/min per mg protein), some other ferrichrome-type compounds are reduced. However, ferrichrome, ferrirubin coprogen B and ferrioxamine are poor substrates. When the mucelia were grown in a medium containing 10(-5) M ferri iron, the activity of the reductase was found to be only 30% of that found under low iron conditions. The enzyme is inhibited by oxygen, SH-alkylating agents and partly by some detergents. Unlike the reductase of N. crassa, the corresponding enzyme from Aspergillus fumigatus revealed low reduction of coprogen and high reduction of ferrichrome, indicating genusdependent specificities of sideramine reduction enzymes in fungi. The participation of acids of the citric acid cycle as natural iron acceptors during strong iron deficiency is studied and confirmed by iron uptake measurements on isolated mitochondria.
 ...
PMID:Enzymatic release of iron from sideramines in fungi. NADH:sideramine oxidoreductase in Neurospora crassa. 14 35

Under anaerobic conditions, Propionibacterium pentosaceum reduces nitrate to nitrite until nitrate is exhausted from the medium when nitrite is converted into N2 or N2O. In the presence of nitrate, fermentation patterns for lactate, glycerol and pyruvate were different from those obtained during anaerobic growth without an inorganic electron acceptor. In the presence of these substrates, a drastic decrease in propionate formation was observed, some pyruvate accumulated during growth with lactate, and acetate was produced from glycerol. Acetate production from lactate and pyruvate was not influenced by the presence of nitrate. Furthermore, CO2 was produced by citric acid cycle activity. The fermentation pattern during nitrite reduction resembled that of P. pentosaceum grown anaerobically without an inorganic electron acceptor. Nitrits has a toxic effect, since bacteria inoculated into a medium with 9 mM-nitrite failed to grow. The cytochrome spectrum of anaerobically grown P. pentosaceum was similar with and without nitrate. In membrane fractions of bacteria grown anaerobically with nitrate, cytochrome b functioned in the transfer of electrons from lactate, glycerol I-phosphate and NADH to nitrate. Molar growth yeilds were increased in the presence of nitrate, indicating an increased production of ATP. This could be explained by citric acid cycle activity, and by ocidative phosphorylation coupled to nitrate reduction. Assuming that I mol ATP is formed in the electron transfer from lactate or glycerol I-phosphate to nitrate, and that 2 mol ATP are formed in the electron transfer from NADH to nitrate, YATP values (g dry wt bacteria/mol ATP) were obtained of between 5-0 and 12-6. The higher YATP values were similar to those obtained during anaerobic growth without an inorganic electron acceptor. This supports the assumptions about the efficiency of oxidative phosphorylation for electron transport to nitrate. Low YAPT values were found when high concentrations of nitrite (15 to 50 mM) accumulated, and were probably due to the toxic effect of nitrite.
 ...
PMID:Influence of nitrate on fermentation pattern, molar growth yields and synthesis of cytochrome b in Propionibacterium pentosaceum. 16 6

Skeletal muscle adapts to endurance excerise, such as long distance running, with an increase in the capacity for aerobic metabolism. This is reflected in an increased capacity of whole homogenates and of the mitochondrial fraction of muscle to oxidize pyruvate and long chain fatty acids. Underlying this increase in the ability to obtain energy by respiration is an increase in the levels of a number of mitochondrial enzymes. These include the enzymes involved in fatty acid oxidation, the enzymes of the citric acid cycle, the components of the respiratory chain that link the oxidation of succinate and NADH to oxygen, and coupling factor 1. These increases in mitochondrial enzyme activity appear to be due to an increase in enzyme protein as evidenced by a doubling of the concentration of cytochrome c and a 60% increase in the protein content of the mitochondrial fraction skeletal muscle. Electronmicroscopic studies suggest that increases in both the size and number of mitochondria are responsible for the increase in mitochondrial protein. An alteration in mitochondrial composition also occurs, with some mitochondrial enzymes increasing 2-fold, others increasing only 35% to 60%, while others, including mitochondrial alpha-glycerophosphate dehydrogenase, creatine phosphokinase and adenylate kinase do not increase at all. As a result of these and other exercise induced biochemical adaptations skeletal muscle tends to become more like heart muscle in its enzyme pattern.
 ...
PMID:Adaptation of skeletal muscle to endurance exercise. 17 69

The pathways responsible for ethanol oxidation and the toxic results of its metabolism are reviewed. The predominant pathway for ethanol oxidation at low ethanol concentrations involves alcohol dehydrogenase. However, at high alcohol concentrations, up to 50% of ethanol uptake is 4-methylpyrazole-intensitive. Oxidation of ethanol under these conditions is associated with a change in the steady-stage concentration of catalase-H2O2. Based on recent evidence, we conclude that it is unnecessary to postulate that ethanol is oxidized directly via cytochrome P-450. Acetaldehyde production from ethanol via the microsomal subfraction can be accounted for by the combined activities of catalase-H2O2 and alcohol dehydrogenase. The metabolism of ehtanol via alcohol dehydrogenase produces a marked reduction in the hepatocellular NAD-NADH sytems. This reduction is indirectly responsible for the inhibition of glycolysis, gluconeogenesis, citric acid cycle activity, and fatty acid oxidation and may be related to some of the pathological effects observed following chronic consumption of alcohol. Attempts in inhibit alcohol dehydrogenase with alkylpyrazoles and activate catalase with substrates for peroxisomal H2O2-generating flavoproteins, while successful, may have limited applicability because of the native toxicity of the substrates themselves...
 ...
PMID:Hepatic alcohol oxidation and its metabolic liability. 19 Dec 95

The pyruvate dehydrogenase complex from the photosynthetic bacterium Rhodospirillum rubrum was associated with the membrane fraction both in heterotrophically and photosynthetically grown cells. The complex was separated from the membranes and partially purified by precipitation with MgSO4 and gelfiltration through Sepharose 4B. The purified complex had a specific activity of 1.5-2mumol/min-mg protein and contained the following partial activities: pyruvate dehydrogenase (EC 1.2.4.1), dihydrolipoamide transacetylase (EC 2.3.1.12) and dihydrolipoamide dehydrogenase (EC 1.6.4.3). Contrary to other bacterial pyruvate dehydrogenase complexes, the enzyme complex from R. rubrum revealed no cooperatively between pyruvate binding sites. The kinetic constants (Km) for the overall reaction were (in mM): 0.14 (pyruvate), 0.07 (NAD) and 0.025 (coenzyme A). The Km for thiamine pyrophosphate was dependent on the nature and the concentration of the divalent metal ion (Mn or Mg) present in the reaction mixture, the values ranging from 0.5 to 3 micrometer. NADH was a potent inhibitor (Ki=5 micrometer) of the enzyme complex and the dihydrolipo amide dehydrogenase. The inhibition was competitive with respect to NAD. In addition to its rapid inhibitory effect, NADH also inactivated the enzyme. Cysteine partially protected the enzyme complex against NADH-inactivation. Acetyl-coenzyme A also inhibited the overall reaction (Ki=40 micrometer). The inhibition was dependent on the concentration of coenzyme A, but independent of the concentration of pyruvate. Sugar phosphates, phosphoenolpyruvate, citric acid cycle intermediates and nucleosidephosphates (1 mM) had no pronounced effect on the overall reaction.
 ...
PMID:[Isolation and characterization of a membrane-bound pyruvate dehydrogenase complex from the phototrophic bacterium Rhodospirillum rubrum (author's transl)]. 19 15

This paper deals with studies on tightly coupled mitochondria present in the active citric acid producing mycelium of Aspergillus niger growing in surface and submerged culture. A special homogenizer had been used for rapid extraction of mitochondria. Observation in the electron microscope indicated that some of the isolated mitochondria were probably damaged during preparation. Nevertheless, the crude mitochondrial fraction was capable of coupling phosphorylation to the oxidation of three different substrates tested viz., succinate, citrate and NADH. It was found that yield of mitochondria was greater in submerged mycelium than in the surface mycelium of A. niger.
 ...
PMID:[Characterization of mitochondria of Aspergillus niger from mycelium growing in surface and submerged culture conditions (author's transl)]. 23

1. The contents of some intermediates of glycolysis, the citric acid cycle and adenine nucleotides have been measured in the freeze-clamped locust flight muscle at rest and after 10s and 3min flight. The contents of glucose 6-phosphate, pyruvate, alanine and especially fructose bisphosphate and triose phosphates increased markedly upon flight. The content of acetyl-CoA is decreased after 3min flight whereas that of acetylcarnitine is decreased markedly after 10s flight, but returns towards the resting value after 3min flight. The content of citrate is markedly decreased after both 10s and 3min flight, whereas that of isocitrate is changed very little after 10s and is increased by 50% after 3min. The content of oxaloacetate is very low in insect flight muscle and hence it was measured by a sensitive radiochemical assay. The content of oxaloacetate increased about 2-fold after 3min flight. A similar change was observed in the content of malate. The content of ATP decreased about 15%, whereas those of ADP and AMP increased about 2-fold after 3min flight. 2. Calculations based on O(2) uptake of the intact insect indicate that the rate of the citric acid cycle must be increased >100-fold during flight. Consequently, if citrate synthase catalyses a non-equilibrium reaction, the activity of the enzyme must increase >100-fold during flight. However, changes in the concentrations of possible regulators of citrate synthase, oxaloacetate, acetyl-CoA and citrate (which is an allosteric inhibitor), are not sufficient to account for this change in activity. It is concluded that there may be much larger changes in the free concentration of oxaloacetate than are indicated by the changes in the total content of this metabolite or that other unknown factors must play an additional role in the regulation of citrate synthase activity. 3. The increased content of oxaloacetate could be produced via pyruvate carboxylase, which may be stimulated during the early stages of flight by the increased concentration of pyruvate. 4. The decreases in the concentrations of citrate and alpha-oxoglutarate indicate that isocitrate dehydrogenase and oxoglutarate dehydrogenase may be stimulated by factors other than their pathway substrates during the early stages of flight. 5. Calculated mitochondrial and cytosolic NAD(+)/NADH ratios are both increased upon flight. The change in the mitochondrial ratio indicates the importance of the intramitochondrial ATP/ADP concentration ratio in the regulation of the rate of electron transfer in this muscle.
 ...
PMID:Changes in the contents of adenine nucleotides and intermediates of glycolysis and the citric acid cycle in flight muscle of the locust upon flight and their relationship to the control of the cycle. 43 78


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