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:1.6.5.3 (complex I)
8,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Left anterior descending coronary artery occlusion in anesthetized pigs produced a stable transmural ischemia characterized by a rapid and then sustained loss of blood flow and mechanical function. After 2 h of occlusion, mitochondria from the ischemic area exhibited a 36 +/- 6% drop in state 3 respiratory activity (QO2) supported by the NAD-linked substrates, glutamate plus malate, but only a 5 +/- 3% decrease in QO2 with succinate plus rotenone. The activity of electron transfer complex I (NADH-CoQ reductase) decreased commensurately by 33 +/- 4% with the decrease in QO2 with NAD-linked substrates. Consistent with the nearly unchanged QO2 with succinate plus rotenone, the activities of electron transfer complexes III and IV decreased only slightly by 9 +/- 5% and 9 +/- 4%, respectively. Mitochondrial ATPase (complex V) activity decreased by 48 +/- 2% with little change in its oligomycin sensitivity. A 48% drop in ATPase activity was shown, by means of oligomycin titrations, to correspond to a 32% decrease in NAD-linked substrate supported QO2. The decreases observed in NADH-CoQ reductase and ATPase activities each account nearly quantitatively for the impaired mitochondrial phosphorylating respiration observed during sustained myocardial ischemia. These results suggest that mitochondrial inner enzyme complexes I and V are important sites of cellular injury in myocardial ischemia.
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PMID:Mitochondrial inner membrane enzyme defects in porcine myocardial ischemia. 645 Nov 85

The oxidative and phosphorylative properties of mitochondria isolated from Neurospora crassa were investigated as a function of growth stage. The rates of oxidation of exogenous NADH and NADPH varied independently of each other, thus ruling out the existence of only one unspecific dehydrogenase. Two different pathways were involved in the oxidation of NAD-linked substrates, as indicated by changes in the rate of oxygen uptake, the sensitivity to rotenone, and the efficiency of phosphorylation. One pathway was sensitive to rotenone and involved three energy-coupling sites, whereas the other was resistant to rotenone and bypassed complex I. Our results indicated that the activity of complex I of the respiratory chain increased markedly in the late exponential phase of growth, remained high in the stationary phase, and then decreased when conidiae were formed. In contrast, the activity of the rotenone-resistant bypass was maximal in the early exponential phase. With malate (plus glutamate) as a substrate, the sensitivity to rotenone and the ADP/O ratios were always lower than those observed with other NAD-linked substrates, suggesting a possible cooperation between malate dehydrogenase and the rotenone-resistant pathway. The rate of oxygen uptake measured in the presence of rotenone was significantly increased by the addition of exogenous NAD+, suggesting that added NAD+ could interact with the rotenone-resistant bypass.
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PMID:Properties of mitochondria as a function of the growth stages of Neurospora crassa. 646 22

Extracellularly applied NADH, but not NAD or NADPH, increases the resting membrane potential from -74.1 to -76.6 mV in freshly isolated muscles in the presence of K+ in the incubation medium and from -64.6 to -72.9 mV in muscles equilibrated for 4-6 h in a K+-free solution. The NADH-induced hyperpolarization is blocked by pretreatment of muscles with ouabain, and the inhibitors of plasma membrane NADH dehydrogenase (adriamycin, azide, PCMB, atebrine, DIDS and bleomycin). The effect of NADH is accompanied by the disappearance of NADH from the incubation medium and by decreased membrane resistance. We conclude that NADH hyperpolarization is due to the enhancement of passive membrane permeability, apparently for K+, which might result from the conformational changes in the plasma membrane during the NADH dehydrogenase reaction. The possibility is discussed that NADH dehydrogenase mediates transport of K+ out from the cell using a pathway connected with the transmembrane Na+/K+ pump.
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PMID:Hyperpolarization of mouse skeletal muscle plasma membrane induced by extracellular NADH. 646 61

The addition of a purified mitochondrial pyridine nucleotide transhydrogenase enzyme preparation to complex I (NADH-CoQ reductase) results in a significant increase in the NADPH-AcPyAD+ transhydrogenase activity of the complex without influencing the NADH-AcPyAD+ transhydrogenase activity. When subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence of complex I, the purified transhydrogenase enzyme preparation was found to co-migrate with the Mr = 130,000 (130K) subunit of the NADH-CoQ reductase. Loss of the NADPH-NAD+ transhydrogenase activity of complex I following limited tryptic digestion was associated with a corresponding loss of the 130K subunit from the complex. These results suggest that the 130K subunit of complex I is the specific peptide responsible for the catalysis of the NADPH-NAD+ transhydrogenase activity observed in complex I. Studies have been carried out testing the influence of photoaffinity pyridine nucleotide probes on the NADPH-NAD+ transhydrogenase activity catalyzed at three levels of resolution, i.e. a homogeneous transhydrogenase preparation, a partially resolved membrane preparation (complex I), and an intact mitochondrial membrane preparation (EDTA particles). Such studies have revealed arylazido-beta-alanyl NADP+ (N3'-O-(3-[N-(4-azido-2-nitrophenyl)amino]propionyl)NADP+) to be a potent inhibitor and an active site-directed reagent for NADPH-NAD+ transhydrogenation at all three levels of resolution. On the other hand, arylazido-beta-alanyl NAD+ (A3'-O-(3-[N-(4-azido-2-nitrophenyl)-amino]propionyl)NAD+ does not produce a significant degree of inhibition of NADPH-NAD+ transhydrogenase activities prior to or following photoirradiation. Nevertheless, the NAD+ analogue has been found to specifically label, covalently, the transhydrogenase protein following photoirradiation of an enzyme-analogue mixture. Arylazido-beta-alanyl NAD+ can as well function as a substrate during transhydrogenation by virtue of being able to accept a hydride ion from NADPH. An interpretation of the observed nucleotide photoprobe specificity for interaction at the active site for transhydrogenation is advanced. In this interpretation, an ordered binding of substrate involves an initial NADP(H) (or NADP+ photoprobe) interaction with a hydrophobic region at the transhydrogenation site. This initial reactivity is followed by a positioning of NAD(H) (or the NAD+ photoprobe analogue) above or periphery to the NADP(H) nucleotide present at the active site region. Supportive evidence for this model for transhydrogenation is presented and discussed.
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PMID:The reaction mechanism of the mitochondrial pyridine nucleotide transhydrogenase. A study utilizing arylazido-pyridine nucleotide analogues. 671 79

A soluble NADH dehydrogenase (NADH:ferricyanide oxidoreductase) has been obtained by simple disruption of cells of Thermus aquaticus strain T351, and purified. The enzyme is of low molecular mass, 50 000 Da, and displays many of the properties of the membrane-bound enzyme, including inhibition by both NADH and ferricyanide, and the same Km for ferricyanide. The enzyme contains 0.05 mol of FMN, 0.16 mol of labile sulphur and 2.2 mol of iron per mol of protein. The enzyme is inhibited by NAD and cupferron competitively with ferricyanide, and by ATP (but not ADP) competitively with NADH. The enzyme is particularly thermostable, having a half-life at 95 degrees C of 35 min. The effect of temperature on the molar absorption coefficient and the stability of NADH was determined.
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PMID:A soluble NADH dehydrogenase (NADH: ferricyanide oxidoreductase) from Thermus aquaticus strain T351. 684 28

The ability of mitochondria to take up and retain Ca2+, and thereby to effect the free intracellular concentration of this ion, is well established. More recently, it has been reported (Lehninger, A. L., Vercesi, A., and Bababunmi, E. A. (1978) Proc. Natl. Acad. Sci. U. S. A. 75, 1690-1696) that the redox state of pyridine nucleotides modulates mitochondrial Ca2+ balance, since the oxidation of mitochondrial NAD(P)H is associated with the release of Ca2+ from these organelles. The latter may be achieved by a variety of treatments including the incubation of Ca2+-loaded liver mitochondria with hydroperoxides, the metabolism of which by the glutathione peroxidase-glutathione reductase system results in NADPH consumption. The metabolism of menadione (2-methyl-1,4-naphthoquinone) by Ca2+-loaded rat liver mitochondria results in rapid oxidation and loss of pyridine nucleotides and a decrease in ATP level. It is also associated with Ca2+ release and an impaired ability of the mitochondria to take up and retain Ca2+. The effects of menadione on mitochondrial Ca2+ balance are more rapid and pronounced than those of t-butylhydroperoxide, and in contrast to those observed with the hydroperoxide, they are not abolished by pretreatment with a glutathione-depleting agent. The effects of menadione on Ca2+ homeostasis are probably initiated by NAD(P)H oxidation linked to the reduction of menadione by both NADH-ubiquinone oxidoreductase and NAD(P)H:(quinone-acceptor) oxidoreductase.
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PMID:The metabolism of menadione impairs the ability of rat liver mitochondria to take up and retain calcium. 711 97

This paper presents biochemical data upon a young male with a mitochondrial myopathy characterised by weakness, severe exercise intolerance, muscle wasting and exercise-induced lactic acidaemia. Two similar cases have been previously documented (Morgan-Hughes et al. 1979). This report more precisely locates the mitochondrial defect. In vitro mitochondrial studies show markedly decreased respiratory rates with all NAD-linked substrates whilst that with flavin-linked succinate is normal. Oxidative phosphorylation is normally coupled. Mitochondrial cytochrome components as determined by low temperature spectroscopy are normal. NADH-ferricyanide reductase and primary dehydrogenase activities are present at levels far in excess of that required to support normal NAD-linked substrate oxidation rates. Intramitochondrial NAD levels are similar to those found in other mammalian muscle. It is proposed therefore that the mitochondrial defect is situated between NADH dehydrogenase and the CoQ--Cytochrome b complex; possibly being a derangement of a non-haem iron sulphur centre.
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PMID:Mitochondrial myopathy. Biochemical studies revealing a deficiency of NADH--cytochrome b reductase activity. 722 53

The interaction of xanthomegnin, a quinone pigment, with the mitochondrial respiratory chain was demonstrated. Xanthomegnin was reduced by succinate, in the presence of submitochondrial particles or mitochondria, only after all oxygen had been consumed in the system, and the reduction was inhibited by antimycin A or KCN. Xanthomegnin was immediately reduced by NADH in a similar system, the reduced xanthomegnin was reoxidized by oxygen but the reduction by NADH was not inhibited by antimycin A or KCN. Xanthomegnin was also immediately reduced by NADH catalyzed by a purified particulate NADH dehydrogenase complex showing a molar ratio of 2 moles NADH for one mole of xanthomegnin. Reoxidation of the reduced pigment by oxygen occurred in this system. Oxygen consumption was accelerated when xanthomegnin was added to a reaction medium containing NADH, NADH segment and cytochrome c oxidase. Subsequent addition of cytochrome c resulted in a further marked acceleration of oxygen consumption. These results suggest that xanthomegnin interacts with the NAD-linked respiratory chain to produce a xanthomegnin shunt, but this does not occur with the succinate-linked chain.
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PMID:The interaction of a quinone pigment, xanthomegnin, with the mitochondrial respiratory chain. 726 94

Isoniazid (INH) interacts with nicotinamide adenine dinucleotide (NAD+) in the regulation of reduced NAD (NADH) oxidation in electron transport particles from Mycobacterium phlei. the interaction was shown to be at the level of the NADH dehydrogenase by the use of menadione as an artificial electron acceptor. Binding studies indicated that INH and NAD+ did not compete for a common regulatory site. Unlabeled INH was unable to displace [14C]NAD+ from electron transport particles, and unlabeled NAD+ could not remove [3H]INH from particles. Preincubation of electron transport particles with unlabeled INH did not prevent the subsequent binding of [14C]NAD+, and unlabeled NAD+ did not block the binding of [3H]INH. [14C]NAD+ binding to electron transport particles was specific and reversible. Unlabeled NAD+ could both displace and prevent the binding of labeled nucleotide. Binding of [14C]NAD+ to electron transport particles was proportional to the incubation concentration of label, and NAD+ stimulation of NADH oxidase activity was related to the amount of NAD+ bound to electron transport particles. [3H]INH was irreversibly bound to electron transport particles. INH and NAD+, although operating at the same level of the electron transport chain, did not appear to compete for the same regulatory site.
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PMID:Site of action of isoniazid on the electron transport chain and its relationship to nicotinamide adenine dinucleotide regulation in Mycobacterium phlei. 742 5

1. Chronic marginal riboflavin deficiency was induced in groups of weanling rats by feeding a deficient diet supplemented with 0, 0.5, 1.0 and 1.5 mg riboflavin/kg diet. Ad lib.- and pair-fed controls received 3.0 and 15 mg riboflavin/kg diet respectively. 2. Serial measurement of erythrocyte NAD(P)H2 glutathione oxidoreductase (glutathione reductase; EC 1.6.4.2) and its activation coefficient revealed that after 12 weeks a steady-state of deficiency had been reached following initial fluctuations in status; the animals were then killed, and their tissues analysed. 3. Food intake, growth rate and the appearance of pathological signs were directly proportional to riboflavin content; however relative liver weight was increased above control levels only in the most-severely-deficient group, and anaemia was not detected in any group. 4. The activation coefficient of glutathione reductase in erythrocytes and liver was closely related to dietary riboflavin content; that of skin responded maximally even in the least-severely-depleted animals. 5. Hepatic and renal flavin contents were directly proportional to dietary riboflavin, FAD being conserved at the expense of riboflavin and FMN. ATP:riboflavin 5-phosphotransferase (flavokinase; EC 2.7.1.26) activity was reduced, even in the least-severely-deficient animals; ATP:FMN adenylyltransferase(FAD pyrophosphorylase; EC 2.7.7.2) was increased in liver, but only in the most-severely-deficient animals. 6. Hepatic succinate:(acceptor) oxidoreductase (succinate dehydrogenase; EC 1.3.99.1) activity fell sharply between 1.5 and 0.5 mg riboflavin/kg diet, producing an S-shaped dose-response curve; it showed smaller or less specific changes in other tissues such as brain, skin and intestine. NADH:(acceptor) oxidoreductase (NADH dehydrogenase; EC 1.6.99.3) activity declined in liver and intestine, but not in skin or brain. 7. The activation coefficient of glutathione reductase was correlated strongly with nearly all the riboflavin-sensitive variables measured, once equilibrium had been reached in this chronic deficiency model, and it was particularly strongly correlated with hepatic and renal FAD levels. Under equilibrium conditions, therefore, it appears to represent a good index of the extent of riboflavin deficiency, and significant changes in flavin levels and enzymes in the internal organs were detected even under conditions of marginal deficiency, associated with relatively small increases in the activation coefficient.
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PMID:A biochemical evaluation of the erythrocyte glutathione reductase (EC 1.6.4.2) test for riboflavin status. 2. Dose-response relationships in chronic marginal deficiency. 747 Apr 38


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