Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A membrane-bound NADH dehydrogenase, solubilized and partially purified from a marine bacterium Photobacterium phosphoreum, contains FAD as the prosthetic group, and is specific for NADH. Ferricyanide, various other redox dyes and cytochrome c can act as electron acceptors. The enzymatic activity when assayed with electron acceptors other than cytochrome c, is activated by monovalent cations (Na+ and K+) and deactivated by high concentrations of monovalent anions (SCN-, NO3-, and Cl-) but not by phosphate ions. The enzymatic reaction follows a ping-pong mechanism and kinetic analysis of the enzyme showed that the activation by monovalent cations is due to increase of affinity of the enzyme for substrates; Vm was not affected. The increase of affinity was 62- and 46-fold for NADH and 57- and 31-fold for 2,6-dichlorophenol indophenol in the presence of Na+ and K+, respectively. On the other hand, NADH-cytochrome c reductase activity of the enzyme was strongly inhibited by these cations.
J Biochem 1978 Sep
PMID:Properties and kinetics of salt activation of a membrane-bound NADH dehydrogenase from a marine bacterium Photobacterium phosphoreum. 72 93

A combined effect of cholesterol and polychlorinated biphenyls (PCBs) on the microsomal drug hydroxylation and glucuronidation in the liver of the rat was studied. PCBs, Clophen A-50 and A-60, having an average chlorination degree of 50 and 60% affect the structure of microsomal membranes. It was found that Clophen A-60 increased the binding of trypsin- and digitonin-sensitive proteins to the membranes. Also it was found that PCBs enhanced the phsopholipid content of microsomes. PCBs increased the activity of hepatic NADPH cytochrome c reductase about 1.5-fold. Aryl hydrocarbon hydroxylase activity doubled with Clophen A-50 and quadrupled with Clophen A-60. Hepatic UDPglucuronosyltransferase activity was doubled with both PCBs. The enhancement in hepatic aryl hydrocarbon hydroxylase and in UDPglucuronosyltransferase was found to be lower in the presence of high cholesterol level in the diet when compared to earlier results. This is supposed to be due to the membraneous effects of cholesterol.
Toxicology 1975 Sep
PMID:Enhancement of hepatic drug biotransformation rate by polychlorinated biphenyls in rats fed cholesterol-rich diet. 81 Sep 23

The effects of intra-articular injections of non-radioactive and tritium-labelled glyceryl trioleate into the mandibular and knee joints of adult rabbits have been investigated using autoradiographic and histochemical techniques and electron microscopy. As observed at the fourth day after operation, fat droplets accumulate in cells of the fibrous, intermediate and cartilaginous layers of mandibular condylar, and in the superficial and upper middle (rather than the deeper) zones of femoral condylar cartilage. Autoradiography of frozen sections shows that numerous silver grains are located over these fat-laden cells following injection of trioleate which has been labelled in the fatty acid moiety of the molecule. In the knee joint the number of grains is directly related to the amount of lipid in the cell. Following injection of glyceryl-labelled trioleate no such result is obtained; it seems doubtful whether or not there is any uptake of this label. However, synovial membrane from the knee joint appears to take up both kinds of trioleate. Results of histochemical methods of NADH diaphorase, lactic dehydrogenase, acid phosphatase and beta-glucosaminidase are consistent with ultrastructural evidence of degeneration in some chondrocytes and of loss of ground substance from the matrix. A raised level of alpha-glycerophosphate dehydrogenase activity is probably associated with synthesis of endogenous glycerol for re-esterification of absorbed fatty acids, and enhanced activity of UDPglucose dehydrogenase with the chondrocytic reaction to matrix depletion. Apart from the increase in fat content, ultrastructural features in injected knee joints include flattening of cell processes against the chondrocyte surface and more abundant intracytoplasmic filaments. Injected mandibular joints show little evidence of these changes although the number of cells in the cartilage appears to be greatly reduced. No extracellular fat droplets occur in femoral cartilage, but material similar in electron density to intracellular fat is observed at the external aspect of some mandibular chondrocytes. The findings indicate that the fatty acid portion of triglyceride injected intra-articularly is taken up by the chondrocytes and retained until at least the fourth day after injection. It is suggested that prior lipolysis takes place either in the synovial cavity (or membrane) or at the chondrocyte surface, but it is uncertain how or in what form fat traverses the matrix. Lipoarthrosis appears to produce changes in the chondrocytes which are thought to be pathological; a number of cell deaths occur. The possibility that gross degeneration of the articular cartilage may ensue is subject to further investigation.
J Anat 1976 Sep
PMID:Changes in articular cartilage following intraarticular injection of tritiated glyceryl trioleate. 97 82

1. Anti-heart mitochondria autoantibodies were developed in serum from dogs following experimental myocardial infarction. 2. Heart mitochondria frozen and thawed repeatedly in a sucrose/Tris-chloride buffer retained both their functional integrity as measured by the respiratory control ratio and their ability to serve as an antigen in a complement fixation test. Mitochondria frozen and thawed in a potassium chloride/Tris-chloride buffer lost both their functional integrity and their autoantigenic activity after one freeze-thaw cycle. 3. Extraction of the heart mitochondria with acetone/water mixtures to remove phospholipids from the membrane led to a complete loss of the ability of the mitochondria to react in the complement fixation test but did not affect the ability of the membranes to bind autoantibody in absorption experiments. 4. Treatment of the mitochondrial membranes with increasing concentrations of trypsin caused a loss of up to approximately 50% of the membrane protein with a gradual decrease in the autoantigenic activity of the membrane without impairment of the ability of the membrane to bind autoantibody. 5. Removal of up to 90% of the sialic acid of the mitochondrial membrane with neuraminidase resulted in a considerable increase in the complement-fixing autoantigenic activity of the membrane without changing the apparent ability of the membrane to bind autoantibody in absorption experiments. 6. Exposure of mitochondrial membranes to autoantibody and complement caused an inhibition of both an inner mitochondrial membrane enzyme, i.e. cytochrome oxidase (48%) and an outer mitochondrial membrane enzyme, i.e. NADH cytochrome c reductase (rotenone insensitive) (37%).
Biochim Biophys Acta 1975 Sep 02
PMID:Characterization of autoantigenic sites on isolated dog heart mitochondria. 118 45

The major mitochondrial processing activity removing presequences from nuclear encoded precursor proteins is present in the soluble fraction of fungal and mammalian mitochondria. We found that in potato, this activity resides in the inner mitochondrial membrane. Surprisingly, the proteolytic activity co-purifies with cytochrome c reductase, a protein complex of the respiratory chain. The purified complex is bifunctional, as it has the ability to transfer electrons from ubiquinol to cytochrome c and to cleave off the presequences of mitochondrial precursor proteins. In contrast to the nine subunit fungal complex, cytochrome c reductase from potato comprises 10 polypeptides. Protein sequencing of peptides from individual subunits and analysis of corresponding cDNA clones reveals that subunit III of cytochrome c reductase (51 kDa) represents the general mitochondrial processing peptidase.
EMBO J 1992 Sep
PMID:The general mitochondrial processing peptidase from potato is an integral part of cytochrome c reductase of the respiratory chain. 132 69

In this paper, we present the nucleotide sequence of a 5248 bp-long region of the mitochondrial (mt) genome of the dermatophyte Trichophyton rubrum. This region which represents about 1/4 of the total mt genome of this species reveals a compact organization of genes including: the glutaminyl tRNA, the methionyl tRNA, the cytochrome oxidase subunit I gene, the arginyl tRNA, the mitochondrial version of the ATPase subunit 9 gene, the cytochrome oxidase subunit II gene and a part of the NADH dehydrogenase ND4L and ND5 gene "complex". The main features of the part of mt DNA sequenced is the non-interrupted COXI gene and the presence in the mitochondrial version of the ATPase 9 gene of a small group IA intron. The extensive amino-acid sequence similarity with the equivalent gene in Aspergillus nidulans and Neuropora crassa indicates that this gene codes for a dicyclohexylcarbodiimide binding protein. The conserved arrangement of this portion of the mt genome and the presence of tRNAs between the protein-coding genes are compatible with a large polycistronic transcript processed by the excision of tRNAs, or similar secondary structures, as proposed for other fungal or mammalian mt DNAS.
Curr Genet 1992 Sep
PMID:Mitochondrial DNA sequence analysis of the cytochrome oxidase subunit I and II genes, the ATPase9 gene, the NADH dehydrogenase ND4L and ND5 gene complex, and the glutaminyl, methionyl and arginyl tRNA genes from Trichophyton rubrum. 132 16

The mycotoxin citrinin, depressed the phosphorylation efficiency of liver mitochondria as deduced from a decrease of respiratory coefficient and of the ADP/O ratio. Citrinin (1.0 mM) inhibited some enzymes linked to the respiratory chain, namely NADH oxidase and NADH cytochrome c reductase involved with complex I. The activities of enzymes related with other enzymatic complexes of the respiratory chain were either unaffected or enhanced. ATPase activity was inhibited by the mycotoxin. Malate, glutamate, and 2-oxoglutarate dehydrogenases were also inhibited. The transmembrane potential (delta psi), developed by energized mitochondria and depolarization on the addition of ADP, was decreased. The results suggest that citrinin promotes a partial dissipation of the transmembrane potential, different from that resulting from a classical uncoupler such as 2,4-dinitrophenol.
Cell Biochem Funct 1992 Sep
PMID:Mechanism of citrinin-induced dysfunction of mitochondria. II. Effect on respiration, enzyme activities, and membrane potential of liver mitochondria. 133 Mar 54

By use of restriction fragment length polymorphism analysis, we examined the liver mitochondrial DNA amplified by polymerase chain reaction from 60 Chinese subjects of 31 to 78 years of age. We found nine specific mtDNA polymorphisms that had never been reported before. Eleven subjects had an Alu I polymorphic site in the subunit 2 gene of NADH dehydrogenase, five had a Hae III polymorphic site in the cytochrome oxidase subunit 2 gene, and five had a Hinf I polymorphic site in the subunit 3 gene of cytochrome oxidase. No polymorphic site was found in the structural genes coding for subunits 1, 3, 4, 4L and 6 of NADH dehydrogenase, cytochrome b, and subunit 8 of ATP synthase. Detailed analysis of the RFLP data did not show age-dependent mtDNA polymorphisms. In addition, the analysis of the restriction patterns of all the mtDNAs revealed 12 mtDNA haplotypes in all the Chinese subjects examined. Among them, type 1 mtDNA was found to be the most predominant and comprised 63.3% of the total study subjects. The restriction patterns of type 1 mtDNA generated by all restriction enzymes were identical to those deduced from the Cambridge sequence of human mtDNA. About 8.3% of the subjects exhibited type 2 mtDNA, and 5% had types 3, 5 and 8 mtDNA, respectively. Each of the rest seven mtDNA types comprised about 2% of the samples. Moreover, type 1 mtDNA was found in the platelets of three white Americans. These findings suggest that type 2 to type 12 mtDNAs have come into existence through the generation or loss of specific polymorphic restriction sites in the mtDNA of the Chinese.
Zhonghua Yi Xue Za Zhi (Taipei) 1992 Sep
PMID:Specific restriction fragment length polymorphism in liver mitochondrial DNA of the Chinese. 135 20

Dicumarol, often used as a specific inhibitor of DT diaphorase (NAD(P)H:(quinone-acceptor) oxidoreductase; EC 1.6.99.2), was found to potently inhibit GSH transferases (EC 2.5.1.18). Dicumarol exhibited an IC50 of 11 microM in inhibiting the conjugation of 1-chloro-2,4-dinitrobenzene (50 microM) by GSH transferase GT-8.7, the major hepatic class mu isoenzyme of CD-1 mice. The activities of GT-8.7 and of the class pi isoenzyme, GT-9.0, toward a carcinogenic substrate, 4-nitroquinoline 1-oxide (100 microM), were inhibited by dicumarol with IC50 values of 14 and 9 microM, respectively. Dicumarol also affected GSH peroxidase II activity, inhibiting the reduction of cumene hydroperoxide by GT-10.6, the predominant class alpha GSH transferase of mouse liver, with an IC50 of 14 microM. GSH peroxidase I (EC 1.11.1.9) and GSH peroxidase II activities were resolved by chromatography of liver and testis cytosols. While inhibiting GSH peroxidase II with IC50 of 9-10 microM, dicumarol did not affect the activity of the selenoenzyme, GSH peroxidase I. Whereas several other non-substrate ligands were more potent inhibitors of 1-chloro-2,4-dinitrobenzene conjugation, dicumarol effectively inhibited GSH transferase and GSH peroxidase II activities in the range of dicumarol concentrations frequently used for detection of DT diaphorase action. These results indicate that physiological consequences resulting from the use of supramicromolar concentrations of dicumarol should not be interpreted in terms of DT diaphorase inhibition alone.
Biochem Pharmacol 1992 Sep 01
PMID:Inhibition of mouse glutathione transferases and glutathione peroxidase II by dicumarol and other ligands. 138 26

Ubiquinol-cytochrome-c oxidoreductase has been isolated from potato (Solanum tuberosum L.) mitochondria by cytochrome-c affinity chromatography and gel-filtration chromatography. The procedure, which up to now only proved applicable to Neurospora, yields a highly pure and active protein complex in monodisperse state. The molecular mass of the purified complex is about 650 kDa, indicating that potato cytochrome c reductase occurs as a dimer. Upon reconstitution into phospholipid membranes, the dimeric enzyme catalyzes electron transfer from a synthetic ubiquinol to equine cytochrome c with a turnover number of 50 s-1. The activity is inhibited by antimycin A and myxothiazol. A myxothiazol-insensitive and antimycin-sensitive transhydrogenation reaction, with a turnover number of 16 s-1, can be demonstrated as well. The protein complex consists of ten subunits, most of which have molecular masses similar to those of the nine-subunit fungal enzyme. Individual subunits were identified immunologically and spectral properties of b and c cytochromes were monitored. Interestingly, an additional 'core' polypeptide which is not present in other cytochrome bc1 complexes forms part of the enzyme from potato. Antibodies raised against individual polypeptides reveal that the core proteins are clearly immuno-distinguishable. The additional subunit may perform a specific function and contribute to the high molecular mass which exceeds those reported for other cytochrome-c-reductase dimers.
Eur J Biochem 1992 Sep 15
PMID:Affinity purification of cytochrome c reductase from potato mitochondria. 139 80


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