Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytosolic Ca2+ overload may play a key role in the process of lead-induced retinal injury and degeneration. We report that retinal calcium content was elevated following developmental and in vitro lead exposure. To determine the concentration-dependent effects of Ca2+ (5-1000 nM) on retinal mitochondrial bioenergetics an isolation procedure was developed. Isolated mitochondria were efficiently coupled; had good respiratory control ratios with the NAD-linked substrates, glutamate or pyruvate plus malate (G/M or P/M), and the FAD-linked substrate, succinate plus rotenone (S/R); and possessed a Na+/Ca2+ exchanger. The major finding was that at equimolar [Ca2+] > or = 35 nM, mitochondria were more sensitive to and exhibited a greater degree of inhibition of coupled and uncoupled respiration with NAD-linked substrates compared to S/R. At all [Ca2+], decreases in State 3 and uncoupled respiration were similar, thereby eliminating the ATP synthase and ADP/ATP translocase as sites of inhibition and suggesting that opening the mitochondrial permeability transition pore (MTP) did not contribute to the inhibition. The effects of toxicological [Ca2+] were: (1) blocked by ruthenium red, (2) blocked by dibucaine only in the presence of NAD-linked substrates, and (3) partially reversed by NAD+ with G/M after opening the MTP. Results with G/M suggest that Ca2+ acts on the inner membrane phospholipase A2 to decrease NADH CoQ reductase activity and/or produce a NAD+ leak, whereas with S/R, Ca2+ may inhibit succinate dehydrogenase. In conclusion, Ca2+ inhibits retinal mitochondrial ATP production, which may contribute to the retinal cell injury and death observed in developmentally lead-exposed rats.
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PMID:Substrate-dependent effects of calcium on rat retinal mitochondrial respiration: physiological and toxicological studies. 817 38

It has been postulated that oxidatively modified low-density lipoprotein (LDL) contributes to the genesis of atherosclerosis. Ubiquinone has been suggested to be an important physiological lipid-soluble antioxidant and is found in LDL fractions in the blood. We measured plasma level of ubiquinone using high-performance liquid chromatography and plasma levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides in 245 normal subjects (186 males, 59 females) and in 104 patients (55 males, 49 females) who had coronary artery disease not receiving pravastatin and 29 patients (12 males, 17 females) receiving pravastatin. In the normal subjects, the plasma ubiquinone levels did not vary with age. In the patient groups, the plasma total cholesterol and LDL levels were higher and the plasma ubiquinone level lower than in the normal subject group. The LDL/ubiquinone ratio was higher in the patient groups. We found that ubiquinone level, either alone or when expressed in relation to LDL levels, was significantly lower in the patient groups compared with the normal subject group. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor is thought to prevent atherosclerosis, however, it also inhibits ubiquinone production. The present study revealed that HMG CoA reductase inhibitor decreased plasma cholesterol level, and that it did not improve either the ubiquinone level or the LDL/ubiquinone ratio. From these results, the LDL/ubiquinone ratio is likely to be a risk factor for atherogenesis, and administration of ubiquinone to patients at risk might be needed.
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PMID:Coenzyme Q10 and coronary artery disease. 824 93

The amino acid sequence of NADH CoQ reductase subunit IV is highly homologous with those of enzymes such as ATPase, argininosuccinate synthetase and adenylate kinase. Replacement of arginine by histidine in three enzymes was shown to result in loss of enzyme activity, causing pathologies including citrullinemia. As an analogy, we submit the hypothesis that replacement of arginine by histidine in NADH CoQ reductase subunit IV leads to its activity change, and ultimately results in Leber's hereditary optic neuropathy.
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PMID:Sequence homology of NADH CoQ reductase subunit IV with nucleotide-requiring enzymes. 832 Aug 63

This study was undertaken to determine if long-term oral administration of lovastatin (50 mg/kg per day) or fenofibrate (200 mg/kg per day) was affecting ubiquinone levels in the heart and the liver of cardiomyopathic hamsters. After 23 weeks of treatment, ubiquinone concentrations (CoQ9 + CoQ10) and ubiquinone ratio (CoQ10/CoQ9) were determined in the heart and in the liver. Our results indicate that lovastatin significantly decreased ubiquinone concentrations in the heart (-33%, P < 0.01) but not in the liver (-23%, NS) when compared to controls, whereas fenofibrate did not alter these parameters. Ubiquinone homologues were not equally decreased during lovastatin treatment: the ratio between CoQ10 and CoQ9 was significantly lowered in the heart (-33%, P < 0.001) and in the liver (-75%, P < 0.001) of lovastatin-treated animals. These results suggest that 3-hydroxymethylglutaryl-coenzyme A reductase inhibition (HMG-CoARI) associated with lovastatin treatment in cardiomyopathic hamsters is more marked in the liver than in the heart, while ubiquinone concentrations are more decreased in cardiac than in hepatic tissues. Our data also showed that fenofibrate had no effect on ubiquinone levels.
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PMID:Effect of a long-term treatment with lovastatin or fenofibrate on hepatic and cardiac ubiquinone levels in cardiomyopathic hamster. 833 56

The assay of Complex I activity requires the use of artificial acceptors, such as short-chain coenzyme Q homologs and analogs, because the physiological quinones, such as CoQ10, are too insoluble in water to be added as substrates to the assay media. The medical interest raised in the last years on the pathological changes of Complex I activity has focussed on the requirement of easy reliable assays for its analysis. We have undertaken a systematic examination of the assay conditions of Complex I in mitochondrial membranes, using a series of quinones as electron acceptors, particularly the coenzyme Q homologs CoQ0, CoQ1 and CoQ2, and the analogs duroquinone and decylubiquinone. Our findings have pointed out that the most suitable electron acceptor for the NADH:CoQ reductase assay is the homolog CoQ1. The analog DB, commercially available, although yielding a high activity, nevertheless causes some problems for the standardization of the assay conditions.
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PMID:Assay conditions for the mitochondrial NADH:coenzyme Q oxidoreductase. 840 27

The antimicrobial mechanism of totarol was studied using Pseudomonas aeruginosa IFO 3080. This diterpene inhibited oxygen consumption and respiratory-driven proton translocation in whole cells, and oxidation of NADH in membrane preparation. NADH-cytochrome c reductase was inhibited by totarol while cytochrome c oxidase was not. NADH-DPIP reductase and NADH-CoQ reductase were also inhibited. The site of respiratory inhibition of totarol was thought to be near CoQ in the bacterial electron transport chain.
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PMID:Mode of antibacterial action of totarol, a diterpene from Podocarpus nagi. 865 42

The redox state of the carriers of electron-transport chain of cardiac mitochondria was studied in the conditions of normal perfusion, global ischemia and reoxygenation of the myocardial tissue. Experiments were performed on isolated rat hearts perfused at 37 degrees C by the "working heart" procedure. The EPR spectra of the freeze-clamped hearts were measured at 6-30 K. An analysis of the main values of g-tensor, line-shape, line-width and relaxation parameters of the components of low-temperature EPR spectra allowed to distinguish the signals from Fe-S centers of NADH-CoQ reductase and succinate-CoQ reductase, and the signals from free radical species of coenzyme Q and flavin coenzymes. The EPR spectra of hearts that were fixed during control perfusion and reperfusion contained predominantly the signal of oxidized S3 center of succinate-CoQ reductase. The free radical signal in these conditions was mainly due to ubisemiquinones. Besides the intensive signal of S3 center, the low-temperature EPR spectra contained also signals from different Fe-S centers paramagnetic in reduced state. The global ischemia of cardiac muscle caused essential reduction of the Fe-S clusters of the mitochondrial electron-transport chain. In ischemic condition the free radical EPR signal was mainly due to flavosemiquinones. The changes of the redox state of carriers of the mitochondrial respiratory chain correlated with the changes of the physiological parameters of cardiac muscle.
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PMID:[Redox state of the electron-transport carriers in cardiac mitochondria: a study by the method of low-temperature EPR spectroscopy]. 949 Jan 10

We investigated the ability of plasma membrane CoQ reductase (PMQR) purified from pig liver to reduce phenoxyl radicals of a vitamin E homologue, Trolox. We report that NADH-driven one-electron reduction of CoQ0 catalyzed by PMQR produced CoQ0 semiquinone radical and CoQoH2. These in turn, recycle vitamin E homologue, Trolox, via reducing its phenoxyl radical. A significant part of NADH/PMQR-catalyzed reduction of CoQ0 (and Trolox recycling) was superoxide-dependent. Overall, our results demonstrate that PMQR in the model system used can act as an antioxidant enzyme that recycles water-soluble homologues of coenzyme Q and vitamin E.
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PMID:Plasma membrane NADH-coenzyme Q0 reductase generates semiquinone radicals and recycles vitamin E homologue in a superoxide-dependent reaction. 964 71

Many lower eukaryotes can survive anaerobic conditions via a fermentation pathway that involves the use of the reduction of endogenously produced fumarate as electron sink. This fumarate reduction is linked to electron transport in an especially adapted, anaerobically functioning electron-transport chain. An aerobic energy metabolism with Krebs cycle activity is accompanied by electron transfer from succinate to ubiquinone via complex II of the respiratory chain. On the other hand, in an anaerobic metabolism, where fumarate functions as terminal electron acceptor, electrons are transferred from rhodoquinone to fumarate, which is the reversed direction. Ubiquinone cannot replace rhodoquinone in the process of fumarate reduction in vivo, as ubiquinone can only accept electrons from complex II and cannot donate them to fumarate. Rhodoquinone, with its lower redox potential than ubiquinone, is capable of donating electrons to fumarate. Eukaryotic fumarate reductases were shown to interact with rhodoquinone (a benzoquinone), whereas most prokaryotic fumarate reductases interact with the naphtoquinones menaquinone and demethylmenaquinone. Fumarate reductase, the enzyme essential for the anaerobic functioning of many eukaryotes, is structurally very similar to succinate dehydrogenase, the Krebs cycle enzyme catalysing the reverse reaction. In prokaryotes these enzymes are differentially expressed depending on the external conditions. Evidence is now emerging that also in eukaryotes two different enzymes exist for succinate oxidation and fumarate reduction that are differentially expressed.
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PMID:The electron transport chain in anaerobically functioning eukaryotes. 969 24

A combination of electrophysiological, pathological, and biochemical studies were performed in myopathy induced by 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors. Simvastatin (a lipophilic inhibitor) or pravastatin (a hydrophilic inhibitor) were administered by gavage to rabbits. In Group I (simvastatin-treated group, 50 mg/kg/day for 4 weeks), four rabbits showed muscle necrosis and high serum creatine kinase (CK) levels, and all six rabbits showed electrical myotonia. In Group II (pravastatin-treated group, 100 mg/kg/day for 4 weeks), no rabbit showed either condition. In Group III (pravastatin-treated group, 200 mg/kg/day for 3 weeks plus 300 mg/kg/day for 3 weeks), one rabbit showed muscle necrosis and high serum CK level and two rabbits showed electrical myotonia. The pathological findings were muscle fiber necrosis and degeneration with increased acid phosphatase activity by light microscopy, autophagic vacuoles and mitochondrial swelling, and disruption and hypercontraction of myofibrils by electron microscopy. Ubiquinone content decreased in skeletal muscle by 22 to 36% in Group I, by 18 to 52% in Group II, and by 49 to 72% in Group III. However, mitochondrial enzyme activities of respiratory chain were normal in all groups. These results indicate that myopathy was not induced by a secondary dysfunction of mitochondrial respiration due to low ubiquinone levels.
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PMID:Myopathy induced by HMG-CoA reductase inhibitors in rabbits: a pathological, electrophysiological, and biochemical study. 977 5


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