Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development of a mitochondrial membrane permeability triggered by the Ca(2+)-stimulation of PLA2 (phospholipase A2; EC 3.1.1.4.) and based on swelling, polyunsaturated fatty acids release and calcium influx, induced the activation of SDH (succinate dehydrogenase; EC 1.3.9.9.) without damaging mitochondria structures. The activity of SDH increased within the length of permeabilization treatment before reaching a plateau. The study of Km and Vm showed that the affinity of SDH for succinate and the maximal velocity were increased. Based on these results, the change of SDH activity triggered under these conditions could be explained by a substrate activation of SDH taking account that the succinate content was significantly enhanced.
Biochem Mol Biol Int 1994 Oct
PMID:Study of the succinate dehydrogenase activation in permeabilized mitochondria through the Ca(2+)-stimulated phospholipase A2. 783 34

This study aimed to compare the metabolic and secretory responses of pancreatic islets from animals with non-insulin-dependent diabetes to D-glucose with the effects of the methyl esters of succinic acid (SME) and glutamic acid (GME). The insulin secretory response to D-glucose was impaired in islets from rats with diabetes which was either inherited (Goto-Kakizaki (GK) rats) or acquired (streptozotocin-treated (STZ) rats). This coincided with a preferential alteration of oxidative relative to total glycolysis in intact islets and a selective defect of FAD-linked mitochondrial glycerophosphate dehydrogenase (m-GDH) in islet homogenates. This enzymatic defect was also found in purified B cells from STZ rats. It contrasted both with unaltered activities of glutamate dehydrogenase and succinate dehydrogenase in the islets of diabetic animals and with a normal or even increased activity of m-GDH in the livers of GK and STZ rats. The oxidation of [1,4-14C]SME and [U-14C]GME appeared decreased in islets of GK or STZ animals when compared with control rats, but no significant difference between control and diabetic rats was observed when the oxidative data were expressed relative to the rate of [U-14C]GME hydrolysis. Nevertheless, the absolute values for insulin release evoked by a non-metabolized analogue of L-leucine (BCH), by SME and by the association of BCH with either SME or GME were invariably lower in islets of GK and STZ rats than in those of control animals.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Endocrinol 1994 Oct
PMID:Pancreatic islet response to dicarboxylic acid esters in rats with type 2 diabetes: enzymatic, metabolic and secretory aspects. 784 32

The enzymes involved in the catabolism of malate namely fumarate reductase, NADH oxidase, "malic" enzyme, succinate dehydrogenase and fumarase as well as NADPH:NAD transhydrogenase, which is involved in the electron transport chain, were studied in Hymenolepis diminuta, a rat intestinal tapeworm. Among cations, K+ had no effect on any enzyme whereas Ca2+ and Mg2+ showed an increase or decrease of varying degrees of different enzyme activities. Most of the compounds, which have been synthesized by the Central Drug Research Institute, Lucknow (India) and found to possess some anthelmintic properties, strongly inhibited the above enzymes except malic enzyme.
Biochem Mol Biol Int 1994 Sep
PMID:Effect of cations and anthelmintics on enzymes of respiratory chains of the cestode Hymenolepis diminuta. 784 34

The PutA protein of Escherichia coli has two enzymatic activities: proline dehydrogenase (PDH) and delta 1-pyrroline-5-carboxylate dehydrogenase (P5CDH). It associates with the cytoplasmic membrane as PDH and P5CDH and with put control region DNA as put repressor. Reduction of the PutA flavin by proline, a PutA conformational change and association of PutA with membranes are coincident. The nucleotide base sequence of E. coli putA was determined, that of S. typhimurium putA was updated and the deduced PutA protein sequences were surveyed for catalytic domains and ligand binding sites. The two sequences were very similar (80.5% and 95% on the nucleic acid and protein levels, respectively). Residues 650 through 1130 of PutA were very similar to the sequences of P5C dehydrogenases and aldehyde dehydrogenases from both prokaryotes and eukaryotes. Glutamate 883 and cysteine 917 of PutA were conserved with the corresponding residues in P5C dehydrogenases and with those proposed to be active site residues in the aldehyde dehydrogenases. Those relationships suggest that gamma-glutamic semialdehyde, believed to equilibrate spontaneously with P5C, is the substrate for P5C dehydrogenases. Residues 340 through 590 of PutA were similar in sequence to proline dehydrogenases from Saccharomyces cerevisiae and Drosophila melanogaster. Limited similarities were also found between residues 315 through 357 of PutA and a consensus sequence near a putative active site and FAD-binding region shared by succinate dehydrogenase sequences from several organisms. Since residues 228 through 358 of PutA were similar in sequence to several serine-pyruvate aminotransferases, PutA is proposed to catalyze the hydrolysis of P5C (a Schiff's base intermediate) to gamma-glutamic semialdehyde. A carboxyl-terminal sequence that resembles a leucine zipper motif may be involved in association of PutA with put control region DNA.
J Mol Biol 1994 Nov 11
PMID:Sequence analysis identifies the proline dehydrogenase and delta 1-pyrroline-5-carboxylate dehydrogenase domains of the multifunctional Escherichia coli PutA protein. 796 12

Previous studies have shown the pathogenic effects of grains cultivated in the endemic areas of Keshan disease and selenium is effective in the prevention of this disease. In this study, liver damages induced by feeding grains from an endemic area (endemic diet), and the effects of selenium and alpha-tocopherol supplement were examined. After 3 months on the endemic diet, the amounts of serum enzymes were significantly increased when compared to controls (animals receiving diet from a non-endemic area). Liver enzymes (alkaline phosphatase and choline esterase) were also found to be altered in the serum, further suggesting liver damages in animals on an endemic diet. Supplement of the endemic diet with selenium or alpha-tocopherol reversed the changes in serum enzymes. Increase in lipid peroxidation in the liver of animals on the endemic diet was observed when compared to that in control animals. Selenium and alpha-tocopherol supplements prevented the increase in lipid peroxidation in the liver by the endemic diet. Semi-quantitative histochemical analysis of glutamate dehydrogenase and succinate dehydrogenase in liver tissue showed that the livers of animals on an endemic diet were more sensitive to ischemic damages in vitro. Supplementation of the endemic diet with either selenium or alpha-tocopherol reduced the sensitivity to ischemic damages. The results suggest that increased lipid peroxidation in the liver of rats on an endemic diet may be responsible for liver damages and elevation of serum enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1994 Mar 30
PMID:Effects of selenium and alpha-tocopherol on liver damage induced by feeding grains from an endemic area of Keshan disease in rats. 796 93

The effects of BRB-I-28 and its derivatives (GLG-V-13, SAZ-VII-22 and SAZ-VII-23), a novel group of antiarrhythmic agents, were investigated on the rat heart mitochondrial respiratory chain. The results indicate that BRB-I-28 and its derivatives have concentration-dependent inhibitory effects on NADH oxidase and NADH-CoQ reductase (complex I), but they have no significant effects on succinate oxidase, succinate dehydrogenase (complex II), CoQ-cytochrome c reductase (complex III), cytochrome c oxidase (complex IV), and NADH-K3Fe(CN)6 reductase. The site of inhibition of BRB-I-28 and its derivatives on the respiratory chain was localized between flavoprotein n (FPn) and CoQ, which is similar to the effect of rotenone and several other antiarrhythmic drugs such as amiodarone, propranolol, etc. BRB-I-28 and its derivatives also have significant inhibitory effects on mitochondrial ATPase activity as reported for other antiarrhythmic drugs such as amiodarone, propranolol, quinidine, and lidocaine. However, BRB-I-28 and its derivatives have no direct effects on sarcoplasmic reticulum Ca(2+)-ATPase activity. The inhibitory effects of BRB-I-28 and its derivatives on mitochondrial oxidative phosphorylation may result in the depletion of ATP. This effect, in combination with their effects on Na+,K(+)-ATPase, could possibly produce an increase in Ca2+ concentration in cytosol. This may be another mechanism by which these DHBCN derivatives produce an increase in systemic arterial blood pressure and contractile force of isolated cardiac muscle. On the other hand, inhibition on mitochondrial respiration may account for some of the potential toxic effects of these diheterabicyclo[3.3.1]nonane derivatives.
Res Commun Mol Pathol Pharmacol 1994 Aug
PMID:Effects of novel antiarrhythmic agents, BRB-I-28 and its derivatives, on the heart mitochondrial respiratory chain and sarcoplasmic reticulum Ca(2+)-ATPase. 799 64

The ArcA and Fnr regulators of Escherichia coli, both of which are activated in anaerobic conditions, negatively regulate the sodA gene (coding for manganese superoxide dismutase), but Fnr has no effect on anaerobic sodA expression in a delta arcA delta fnr background (Compan and Touati, 1993). We show here that the sdh gene (coding for succinate dehydrogenase) is also negatively regulated by Fnr, but again Fnr exerts no control in a delta arcA background. One interpretation of these results is that Fnr activates arcA transcription. Using arcA-lac transcriptional and translational fusions, we show that arcA expression increases (about fourfold) in anaerobiosis and that both Fnr and ArcA are required for full expression. In a delta fnr background, there is no autoactivation, suggesting that ArcA enhances activation by Fnr. Transcript and sequence analyses reveal that the arcA upstream regulatory region lies within a 530 bp non-coding DNA fragment, which contains five putative promoter sequences and a putative Fnr-binding site. Identification of the transcription start sites indicates that transcription occurs in aerobiosis from three constitutive upstream promoters (Pe, Pd, Pc). In anaerobiosis an additional completely Fnr-dependent transcript starting at Pa is present; expression from Pa is reduced in the absence of ArcA, and Fnr activation at Pa blocks the weak anaerobic-dependent expression from Pb. Fnr activation of arcA transcription may play an important role in the co-ordination of expression of genes associated with aerobic and anaerobic metabolism during environmental changes.
Mol Microbiol 1994 Mar
PMID:Anaerobic activation of arcA transcription in Escherichia coli: roles of Fnr and ArcA. 802 71

The pathway of NADH oxidation in the procyclic Trypanosoma brucei brucei was investigated in a crude mitochondrial membrane fraction and in whole cells permeabilized with digitonin. NADH:cytochrome c reductase activity was 75% inhibited by concentrations of antimycin that inhibited 95% succinate:cytochrome c reductase activity suggesting that the major pathway for NADH oxidation in the mitochondria involved the cytochrome bc1 complex of the electron transfer chain. Both NADH:cytochrome c and NADH:ubiquinone reductase activities were inhibited 80-90% by rotenone indicating the presence of a complex I-like NADH dehydrogenase in the mitochondrion of trypanosomes. In whole cells permeabilized with low concentrations of digitonin, the oxidation of malate, proline and glucose (in the presence of salicylhydroxamic acid, the inhibitor of the alternate oxidase) was inhibited 30-50% by rotenone. The presence of an alternative pathway for NADH oxidation involving fumarate reductase was indicated by the observation that malonate, the specific inhibitor of succinate dehydrogenase, inhibited 30-35% the rate of oxygen uptake with malate and glucose as substrates in the digitonin-permeabilized cells. We conclude that in the mitochondrion of the procyclic form of T. brucei, NADH is preferentially oxidized by a rotenone-sensitive NADH:ubiquinone oxidoreductase; however, NADH can also be oxidized to some extent by the enzyme fumarate reductase present in the mitochondrion of T. brucei.
Mol Biochem Parasitol 1994 Mar
PMID:Oxidation of NADH by a rotenone and antimycin-sensitive pathway in the mitochondrion of procyclic Trypanosoma brucei brucei. 807 26

The core origin for plus strand DNA replication of filamentous bacteriophage f1 binds the initiator protein (gpII), which subsequently introduces a specific nick in the plus strand. The core origin consists of a nicking region and a binding region. The binding of gpII occurs in two steps, forming a binding intermediate (complex I) and a functional complex for nicking (complex II). Results of gel retardation experiments using circularly permuted DNA fragments and direct visualization by electron microscopy show that gpII induces successive bends within the binding region upon formation of the complexes. We show that gpII binding induces duplex melting in the nicking region using KMnO4 modification of unpaired thymidine residues as a probe for melting. Origin binding occurred in the absence of superhelicity of DNA and Mg2+, whereas duplex melting required superhelical DNA, but not Mg2+. Deletion analyses indicated that hypothetical formation of a cruciform around the nicking site is not necessary for either melting or nicking. A mutation in gpII resulted in stimulation of duplex melting and nicking without showing obvious effects on bending. This suggests that the mechanism of melting involves local interaction between gpII and the nicking region. Furthermore, using synthetic oligonucleotide substrates, we show that the nicking reaction takes place efficiently when the nicking region is single-stranded and the binding region is double-stranded. These results indicate that the nicking reaction is preceded by an ordered series of protein-induced DNA-conformational changes: successive bending of the origin upon gpII binding, followed by duplex melting that requires negative superhelicity.
J Mol Biol 1994 Apr 08
PMID:Multiple DNA conformational changes induced by an initiator protein precede the nicking reaction in a rolling circle replication origin. 815

Computer-assisted structural analysis of the predicted product of the previously described open reading frame (ORF) YKL4 located on the left arm of chromosome XI of Saccharomyces cerevisiae revealed a high degree of similarity (> 50%) to bovine cytochrome b560, the sdhC polypeptide of the Escherichia coli succinate dehydrogenase (SDH) complex and the protein specified by ORF137 located on the chloroplast DNA of Marchantia polymorpha. Disruption of the yeast gene severely impaired mitochondrial function, while Northern analysis showed it to be subject to catabolite repression. Deletion analysis of the CYB3 promoter identified a single HAP2/3/4-binding element that is necessary and sufficient for carbon source-dependent transcriptional regulation. These experiments also suggested the presence of additional, as yet unidentified, transcriptional control elements, both negative and positive. Taken together, these data lead us to conclude that the CYB3 gene encodes the yeast homolog of the bovine cytochrome b560 component of complex II of the mitochondrial electron transport chain.
Mol Gen Genet 1994 Mar
PMID:Characterization of the Saccharomyces cerevisiae nuclear gene CYB3 encoding a cytochrome b polypeptide of respiratory complex II. 815 21


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