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)

Whether pure thiamine deficiency produces a neuropathy in Mammalia is still debated. Rats were pair-fed-synthetic diets with and without thiamine. When studied histochemically, soleus muscles from thiamine-deficient rats showed (1) small, angular fibers that had high NADH dehydrogenase activities; (2) a loss of 43% of type II (FOG) fibers; (3) decreased intensity of the reaction for betaOHB dehydrogenase; and (4) fibers with subsarcolemmal collections resembling "ragged-red" muscle. Electron microscopy revealed degeneration of some small myelin sheaths of distal and intramuscular nerves; atrophic, degenerating, hypoosmophilic muscle fibers in soleus and vastus medialis; and scattered muscle fibers with abnormal collections of deranged mitochondria accompanied by lipid droplets. These abnormalities, not found in control muscles, indicate that both motor neuropathy and mild mitochondrial changes, such as are seen in the "ragged-red" diseases, are induced by pure thiamine deficiency.
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PMID:Experimental thiamine deficiency. Neuropathic and mitochondrial changes induced in rat muscle. 5 58

The hemocytes of the hard clam M. mercenaria were of three types: an agranulocyte, a small, and a large granulocyte. The agranulocyte, with only a thin periphery of cytoplasm surrounding the nucleus, had no visible cytoplasmic granules in living preparations but did exhibit a few centers of nonspecific esterase activity. This cell type represented 2% of the hemocyte population. The small granulocyte possessed four distinct granule types and comprised 61% of the total cell population. Large granulocytes accounted fro 37% of all hemocytes. While they contained the same four granule types identified in the small granulocyte, only one-third the total number were present. The nucleus of all three hemocyte types appeared morphologically similar. The four types of granules observed were a blunt, dot-like, a refractile and a filamentous granule. Blunt granules were identified as mitochondria, based on their ability to reduce Janus Green B to diethyl safranin, the presence of NADH dehydrogenase activity and boundary staining with Sudan black B. Dot-like granules were identified as lysosomes on the basis of neutral red staining, localization of acid phosphatase and nonspecific esterase activity and staining with Sudan black B. Refractile granules were demonstrated to be membrane-bound, lipid-filled structures that reacted positively with Sudan black B and Oil red O, respectively; these granules act as lipid storage centers. Nuclear similarity of the three cell types suggest that these cells might represent different stages of maturity, rather than three distinct cell lines. This was also indicated by the similar yet graded cytochemical reactions and the varying degree of motility and phagocytic activity demonstrated by hemocyte types.
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PMID:Cytochemical aspects of Mercenaria mercenaria hemocytes. 6 87

Measurement of the effect of drugs on the in vivo rates of synthesis of rabbit liver organelle bound proteins were measured following individual treatments with the inducers phenobarbital, 3-methylcholanthrene and PCB (a mixture of polychlorinated biphenyls) and the inhibitors, cycloheximide, aflatoxin B1, chloramphenicol and actinomycin D. Following their isolation from a homogenate containing the combined livers of 14C-leucine injected experimental animals and 3H-leucine injected control animals, purified fractions of the following proteins were prepared: microsomal cytochrome b5, cytochrome P-450, NADH-cytochrome b5 reductase, NADPH-cytochrome P-450 reductase and proteolipids, outer mitochondrial membrane cytochrome b5, NADH-cytochrome b5 reductase and proteolipids, inner mitochondrial membrane cytochrome c, NADH dehydrogenase and proteolipids, intermitochondrial membrane cytochrome b5 and circulating serum albumin. The effect of a drug was examined by measuring the 14C/3H ratio of leucine incorporation of each fraction; ratios which differed markedly from a control value of 1 represented actual changes in the relative rates of protein synthesis. Increased rates of synthesis of cytochrome P-450 and its reductase, intermitochondrial membrane cytochrome b5 and all three proteolipid fractions resulted from each inducer treatment. Treatments with 3-methylcholanthrene and PCB also increased the rate of synthesis of cytochrome b5 and its reductase in both the microsome and outer mitochondrial membrane. In addition, the PCB treatment increased the rates of synthesis of cytochrome c and NADH-dehydrogenase. The rates of synthesis of cytochromes, reductases and of circulating serum albumin were inhibited following treatments with cycloheximide, aflatoxin B1 and actinomycin D. Actinomycin D appeared to inhibit the release of newly synthesized albumin into the bloodstream while chloramphenicol treatment appeared to inhibit the incorporation of cytochrome c into the mitochondria. After 20 hours of treatment with inhibitors, the inhibitory effect of actinomycin D and cycloheximide were still apparent while the rates of protein synt;esis in chloramphenicol and aflatoxin B1 treated animals increased to levels above the controls. The incorporation of radioactively labeled leucine into the proteolipids of the microsomal, and the outer and inner mitochondrial membranes were inhibited following the treatment with actinomycin D and stimulated following the treatment with cycloheximide.
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PMID:Effect of a single dose of inducers and inhibitors on the rate of synthesis of cytochromes and reductases in liver organelles. 11 59

The non-ionic detergent octyl glucoside solubilizes a substantial amount of Streptococcus faecalis membrane protein without loss of the monitored enzyme activities. A secondary detergent, dioctanoyl phophatidycholine, appears to increase the yield of solubilized material. In addition, the effect of ionic strength indicates that it may be possible to selectively extract groups of membrane proteins by their characteristic solubility at different ionic strengths. The solubilized membrane-associated enzymes, ATPase and NADH dehydrogenase, enter polyacrylamide gels as distict species. Electrophoretic studies suggest that there are two membrane-associated ATPase in the Streptococcus faecalis, one which dissociates from the membrane in the absence of Mg-2+ ions and the other which remains particulate until solubilized by detergents. Octyl glucoside can be easily removed from a solution containing solubilized proteins and lipid by dialysis.
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PMID:Solubilization of bacterial membrane proteins using alkyl glucosides and dioctanoyl phosphatidylcholine. 12 71

A new procedure for the isolation of membrane vesicles from Acholeplasma laidlawii cells is described. The membrane vesicles are completely free from contaminations of whole cells and cell debris and represent a homogeneous fraction as shown by electron microscopy, Ficoll density-gradient centrifugation, and titration on agar plate. Absence of cytoplasmic contaminations was confirmed by double-labelling of membranes with 3H-oleic acid and 14C-uridine, as well as by distribution of specific marker enzymes of membranes and cytoplasm. On the basis of light-scattering and electron microscopy, the vesicular nature of these membranes was established. The vesicles had the same orientation as intact cells (absence on membrane vesicles of ATPase and NADH dehydrogenase activities, localized in the inner surface of membrane). The respiratory activity of the membrane vesicles was low and was not stimulated by exogenous substrates, the respiratory chain of the vesicles being reduced and terminated by flavoproteins. The ability of membrane vesicles to take up carbohydrates was shown.
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PMID:Transport properties of membrane vesicles from Acholeplasma laidlawii. I. Isolation and general characteristics. 12 39

Measurement of certain membrane-bound enzymic activities was used to study the orientation of the outer membrane of the double-membraned forespore of Bacillus megaterium KM. 2. Adenosine triphosphatase, NADH dehydrogenase and L-malate intact protoplasts, but were readily detected in intact stage II or IV forespores, consistent with reversed polarity of the outer forespore membrane relative to the mother-cell plasma membrane. 3. Measurement of NADH oxidase activity revealed that intact stage III forespores had the same high affinity for NADH as protoplast membrane preparations and protoplast lystates, consistent with ready access of NADH to oxidation sites on the outer forespores membrane. 4. Forespores and protoplasts showed osmometric behaviour in solutions of non-permanent solutes consistent with the presence of an intact permeability barrier in these structures.
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PMID:Biochemical evidence for the reversed polarity of the outer membrane of the bacterial forespore. 13 69

The molecular architecture of membrane vesicles prepared from Escherichia coli ML 308-225 has been studied by using crossed immunoelectrophoresis, and a reference pattern of 52 discrete immunoprecipitates has been established. Progressive immunoadsorption experiments conducted with untreated control vesicles and with physically disrupted vesicles demonstrate that the membrane-associated immunogens fall into two categories: (i) those immunogens typified by ATPase (ATP phosphohydrolase, EC 3.6.1.3) and NADH dehydrogenase [NADH: (acceptor) oxidoreductase, EC 1.6.99.3] whose expression is minimal unless the vesicles are disrupted; and (ii) immunogens such as Braun's lipoprotein that are expressed to similar extents in untreated and in disrupted vesicles. A mathematical relationship between the peak area subtended by an immunoprecipitate in the crossed immuno-electrophoresis system and the quantity of vesicles used in the adsorption process has been derived. This relationship allows quantitation of the degree to which specific membrane immunogens partition between exposed and unexposed surfaces of the vesicle membrane. The results demonstrate conclusively that >95% of the membrane in the vesicle preparations is in the form of sealed sacculi with the same polarity as the intact cell. Moreover, the findings provide a strong indication that dislocation of immunogens from the inner to the outer surface of the membrane during vesicle preparation does not occur to an extent exceeding 11%.
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PMID:Molecular structure of membrane vesicles from Escherichia coli. 15 May 99

The phospholipid requirement of membrane-bound enzymes may depend on several reasons. In our laboratory we have investigated lipids (1) as a bidimensional medium required for the movement of Coenzyme Q, a lipid-soluble cofactor of the mitochondrial respiratory chain, and (2) as a hydrophobic environment necessary to impose the proper conformation to membrane-bound enzymic proteins. We have found that Coenzyme Q, once reduced by NADH dehydrogenase, must cross the inner mitochondrial membrane; only quinones having long isoprenoid side chains can easily cross phospholipid bilayers, and this is the reason why a short chain quinone such as CoQ-3 inhibits NADH oxidation. The incapability of short quinones to cross lipid bilayers is due to their disposition in the lipid bilayer, stacked within the phospholipids. The conformational role of lipids has been investigated indirectly observing the kinetics of membrane-bound enzymes, e.g. the mitochondrial ATPase, and directly by circular dichroism. Lipid removal or lipid perturbation with organic solvents induce a decrease of alpha-helical content in mitochondrial proteins, and give rise to a series of kinetic changes in ATPase, including uncompetitive inhibition, increased activation energy, and loss of cooperativity in oligomycin inhibition. The recognition of a conformational role of lipids has allowed us to postulate a working hypothesis for the mechanism of action of general anesthetics. Such drugs have been found by us, by means of spin labels and fluorescent probes, to disrupt lipid protein interactions in several membranes, including synaptic membranes. The loosening of such interactions is believed to induce conformational changes, which will alter ion transport systems necessary to the propagation of neural impulses. Conformational changes induced by anesthetics have been found by us both directly by circular dichroism and indirectly by enzyme kinetics. The conformational effect of anesthetics is not directly exerted on the proteins but is mediated through the lipids. In agreement with this hypothesis we have found that membrane-bound acetylcholinesterase is inhibited by anesthetics, whereas the solubilized enzyme is not inhibited. However, binding of the solubilized enzyme to phospholipids restores anesthetic inhibition.
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PMID:Biophysical studies on agents affecting the state of membrane lipids: biochemical and pharmacological implications. 15 58

The plastoquinone antagonist 2,5-dibromothymoquinone was found to inhibit NO-3 reduction from NADH by the nitrate reductase complex from wheat. It accepts electrons from NADH through the NADH dehydrogenase activity of the nitrate reductase. However, it does not inhibit the reduction of 2,6-dichlorophenol-indophenol by the enzyme. This suggests that the two compounds may be accepting electrons at different places from the enzyme. Further it was observed that reduced DCIP could be oxidized by DBMIB in the absence of NADH indicating that the electron flow in the nitrate reductase complex may take place in a unidirectional way.
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PMID:Inhibition of the nitrate reductase complex by dibromothymoquinone. 15 94

1. Respiration of chemotrophically and phototrophically grown Rhodospirillum rubrum is inhibited by 2-hydroxydiphenyl. 2. Membrane-bound NADH oxidase and NADH: cytochrome c reductase are inhibited also. The inhibitor constant for both reactions (Ki) is 0.075 plus or minus 0.012 mM. NADH dehydrogenase is not inhibited significantly. 3. The inhibition of succinate:cytochrome c reductase is associated for chemotrophic membranes with Ki equals 0.22 plus or minus 0.03 mM and for phototrophic membranes with Ki equals 0.49 plus or minus 0.09 mM. Succinate dehydrogenase is not affected by 2-hydroxydiphenyl. 4. Cytochrome oxidase is inhibited only slightly. 5. While NADH-dependent reactions in both phototrophic and chemotrophic membranes are inhibited maximally more than 95 percent, succinate-dependent reactions can be inhibited more than 95 percent only in chemotrophic membranes. In phototrophic membranes the maximum inhibition of succinate-dependent reactions is about 70 percent. 6. The type of inhibition in both cases 2 and 3 is non-competitive. 7. While the reduction of b-type cytochrome is inhibited by 2-hydroxydiphenyl, the degree of ubiquinone reduction is not influenced. The data suggest that the site of inhibition is localized between ubiquinone and cytochrome b. 8. Implications of these data for the respiratory electron transport system in R. rubrum are discussed.
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PMID:Separation of respiratory reactions in Rhodospirillum rubrum: inhibition studies with 2-hydroxydiphenyl. 16 37


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