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:1.8.1.4 (diaphorase)
2,754 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Glutathione reductase and lipoamide dehydrogenase are structurally and mechanistically related flavoenzymes catalyzing various one and two electron transfer reactions between NAD(P)H and substrates with different structures. 2. The two enzymes differ in their coenzyme and functional specificities. Lipoamide dehydrogenase shows higher coenzyme preference while glutathione reductase displays greater functional specificity. 3. Binding preference of the two flavoenzymes for nicotinamide coenzymes is demonstrated by 31P-NMR spectroscopy. 4. The presence of arginines in glutathione reductase which is inactivated by phenyl glyoxal, is likely to be responsible for the NADPH-activity of glutathione reductase. 5. The substrate binding sites of the two enzymes are similar, though their functional details differ. 6. The active-site histidine of glutathione reductase functions primarily as the proton donor during catalysis. While the active-site histidine of lipoamide dehydrogenase stabilizes the thiolate anion intermediate and relays a proton in the catalytic process.
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PMID:Comparative studies of glutathione reductase and lipoamide dehydrogenase. 304 90

The binding protein-dependent transport of galactose and maltose occurs at a reduced but significant rate in Escherichia coli cells which have undergone a mild toluenization. Dihydrolipoate and 3-acetyl-NAD produce a severalfold stimulation of these transports in the toluenized cells. In parallel to the stimulation of galactose and maltose transport by dihydrolipoate and 3-acetyl-NAD, there is a stimulation by galactose and maltose of lipoamide dehydrogenase activities which seem to be related to the binding-protein-dependent transport of these sugars. The lipoamide dehydrogenase component of the pyruvate and 2-oxoglutarate dehydrogenase complexes (the lpd gene product) is not involved in this stimulation. These results are discussed in relation to our recent studies showing a possible involvement of lipoic acid and of the 2-oxoacid dehydrogenases in the binding-protein-dependent transports.
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PMID:Galactose- and maltose-stimulated lipoamide dehydrogenase activities related to the binding-protein-dependent transport of galactose and maltose in toluenized cells of Escherichia coli. 308 52

DL-alpha-difluoromethylornithine (DFMO), a specific irreversible inhibitor of ornithine decarboxylase (ODC), rapidly depletes cells of intracellular putrescine. When administered to animals and humans, DFMO cures acute infections of trypanosomiasis. In order to determine if the mechanism of drug action is related to initiation of transformation and biochemical alterations subsequent to polyamine depletion, trypanosome morphology and mitochondrial activation were studied in a monomorphic strain of Trypanosoma brucei brucei. Exposure of trypanosomes to DFMO in vivo in infected rodents or in vitro in culture resulted in a depletion of intracellular putrescine and a cessation of cell division without specific cytotoxicity. These events were followed by a transformation of the long slender bloodstream form to a short stumpy form via an intermediate morphology. Putrescine, the product of the ODC reaction, abrogates this effect. When introduced into SDM-79 medium, the intermediate form is capable of further transformation to an "insect" procyclic trypomastigote whereas the long slender form and short stumpy form are not. Short stumpy forms are incapable of binary fission and have lost their infectivity for the vertebrate host. In addition, the mitochondrial marker enzyme, NAD diaphorase, was found only in the short stumpy and intermediate forms. We hypothesize that the short stumpy phenotype may not be a viable stage in the natural transformation of the trypanosome from its mammalian host to the insect vector.
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PMID:Polyamine depletion following exposure to DL-alpha-difluoromethylornithine both in vivo and in vitro initiates morphological alterations and mitochondrial activation in a monomorphic strain of Trypanosoma brucei brucei. 309 Feb 40

The results presented in this paper reveal the existence of three distinct menadione (2-methyl-1,4-naphthoquinone) reductases in mitochondria: NAD(P)H:(quinone-acceptor) oxidoreductase (D,T-diaphorase), NADPH:(quinone-acceptor) oxidoreductase, and NADH:(quinone-acceptor) oxidoreductase. All three enzymes reduce menadione in a two-electron step directly to the hydroquinone form. NADH-ubiquinone oxidoreductase (NADH dehydrogenase) and NAD(P)H azoreductase do not participate significantly in menadione reduction. In mitochondrial extracts, the menadione-induced NAD(P)H oxidation occurs beyond stoichiometric reduction of the quinone and is accompanied by O2 consumption. Benzoquinone is reduced more rapidly than menadione but does not undergo redox cycling. In intact mitochondria, menadione triggers oxidation of intramitochondrial pyridine nucleotides, cyanide-insensitive O2 consumption, and a transient decrease of delta psi. In the presence of intramitochondrial Ca2+, the menadione-induced oxidation of pyridine nucleotides is accompanied by their hydrolysis, and Ca2+ is released from mitochondria. The menadione-induced Ca2+ release leaves mitochondria intact, provided excessive Ca2+ cycling is prevented. In both selenium-deficient and selenium-adequate mitochondria, menadione is equally effective in inducing oxidation of pyridine nucleotides and Ca2+ release. Thus, menadione-induced Ca2+ release is mediated predominantly by enzymatic two-electron reduction of menadione, and not by H2O2 generated by menadione-dependent redox cycling. Our findings argue against D,T-diaphorase being a control device that prevents quinone-dependent oxygen toxicity in mitochondria.
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PMID:Menadione- (2-methyl-1,4-naphthoquinone-) dependent enzymatic redox cycling and calcium release by mitochondria. 309 56

The binding protein-dependent galactose transport of Salmonella typhimurium has been reconstituted in proteoliposomes made from a partially purified protein fraction (containing the three membrane protein implicated in this transport and a lipoamide dehydrogenase activity) and soybean phospholipids. The reconstitution of galactose transport requires the addition of the purified galactose binding protein. Transport is energized either by reduced lipoamide and NAD or by the membrane potential and is inhibited by ATP.
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PMID:[Reconstitution of high-affinity galactose transport of Salmonella typhimurium in proteoliposomes: energization by lipoamide and NAD or by the membrane potential; inhibition by ATP]. 311 76

Ferredoxin-NADP reductase from Euglena gracilis Klebs var. Bacillaris Cori purified to apparent homogeneity, yields a typical 36 kDa and an unusual 15 kDa polypeptide on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, exhibits a typical flavoprotein spectrum, contains FAD, and catalyzes NADPH-dependent iodonitrotetrazolium-violet diaphorase, NADPH-specific ferredoxin-dependent cytochrome-c-550 reductase and NADPH-NAD transhydrogenase activities. Rabbit antibody to the purified FNR blocks these activities specifically and also blocks the iodonitrotetrazolium-violet diaphorase activity of Euglena chloroplast completely. The low iodonitrotetrazolium-violet diaphorase activity in the plastidless mutant, W10BSmL, is mitochondrial and is not specifically blocked by the ferredoxin-NADP reductase antibody. Dark-grown non-dividing (resting) wild-type Euglena cells show a 4-fold increase in ferredoxin-NADP reductase activity during greening at 970 lx. Half of the low ferredoxin-NADP reductase activity in dark-grown cells is initially soluble, but by the end of chloroplast development nearly all of the enzyme is membrane-bound. The binding of ferredoxin-NADP reductase on exposure to light correlates with the extent of thylakoid membrane formation. Immunoblots of wild-type extracts during greening indicate that the 15 kDa polypeptide increases in the same manner as the extent of reductase binding to thylakoid membranes.
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PMID:Purification, properties, and cellular localization of Euglena ferredoxin-NADP reductase. 312 Jul 72

An NADPH-specific disulfide reductase that is active with bis-gamma-glutamylcystine has been purified 1,900-fold from Halobacterium halobium to yield a homogeneous preparation of the enzyme. Purification of this novel reductase, designated bis-gamma-glutamylcystine reductase (GCR), and purification of halobacterial dihydrolipoamide dehydrogenase (DLD) were accomplished with the aid of immobilized-metal-ion affinity chromatography in high-salt buffers. Chromatography of GCR on immobilized Cu2+ resin in buffer containing 1.23 M (NH4)2SO4 and on immobilized Ni2+ resin in buffer containing 4.0 M NaCl together effected a 120-fold increase in purity. Native GCR was found to be a dimeric flavoprotein of Mr 122,000 and to be more stable to heat when in buffer of very high ionic strength. DLD was chromatographed on columns of immobilized Cu2+ resin in buffer containing NaCl and in buffer containing (NH4)2SO4, the elution of DLD differing markedly in the two buffers. Purified DLD was found to be a heat-stable, dimeric flavoprotein of Mr 120,000 and to be very specific for NAD. The utility of immobilized-metal-ion affinity chromatography for the purification of halobacterial enzymes and the likely cellular function of GCR are discussed.
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PMID:The novel disulfide reductase bis-gamma-glutamylcystine reductase and dihydrolipoamide dehydrogenase from Halobacterium halobium: purification by immobilized-metal-ion affinity chromatography and properties of the enzymes. 313 40

A simple colorimetric enzymatic assay for determination of serum 12 alpha-hydroxy bile acids was developed using 12 alpha-hydroxysteroid dehydrogenase (HSD). The enzymes were extracted from Bacillus sphaericus. The principle of the method is as follows: 12 alpha-hydroxy bile acids are converted to 12-oxo bile acids using 12 alpha-HSD with the conocomitant reduction of NAD to NADH, and then the hydrogen of the generated NADH is transferred by diaphorase to NTB to yield diformazan. Finally, the color of resultant diformazan was measured. The specificity and precision of this assay method were satisfactory. A linear relationship was noted between the amount of 12 alpha-hydroxy bile acids and the degree of absorbance in the range of 6.7 to 215 microM. The fasting values for serum 12 alpha-hydroxy bile acid in 10 patients with liver diseases ranged widely from 7.6 to 91.1 microM, and values obtained with this assay agreed closely with those obtained by gas-liquid chromatography (r = 0.94, p less than 0.001). The assay is convenient, rapid, and specific for the measurement of 12 alpha-hydroxy bile acid concentrations in the serum of patients with liver diseases.
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PMID:Enzymatic determination of serum 12 alpha-hydroxy bile acid concentration with 12 alpha-hydroxysteroid dehydrogenase. 322 Feb 41

The molecular structure of lipoamide dehydrogenase from baker's yeast has been determined at 4.5 A resolution by molecular replacement techniques using the known structure of human erythrocyte glutathione reductase as a starting model. The enzyme crystallizes in the space group P2(1)2(1)2(1) with a = 98.6(2), b = 162.0(2), c = 69.4(2) A. There is one molecule per asymmetric unit. The enzyme is a dimeric protein of identical subunits related by a local two-fold symmetry. Comparison of the tertiary structures between glutathione reductase and the present enzyme shows that the folding is almost the same except for the N and C termini, although some slight shortening or shifting of alpha-helices was found in the electron density map. FAD molecules are found at similar positions to those of glutathione reductase. Since the amino acid residues around FAD and NAD binding sites and at the reaction centers of the two enzymes are strongly conserved, the lipoamide dehydrogenase may catalyze the opposite reaction through a similar mechanism to that proposed for glutathione reductase. The newly found C terminus is located near the edge of a deep cave at the interface between the two subunits. These additional 18 residues form a narrow entrance to the cave, in which the long chain of the dihydrolipoyl moiety of lipoate acetyltransferase will be bound.
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PMID:X-ray study of baker's yeast lipoamide dehydrogenase at 4.5 A resolution by molecular replacement method. 329 18

A new method permitting the simultaneous evaluation of the redox states of alpha-lipoamide dehydrogenase and electron-transfer flavoprotein in intact rat liver mitochondria by two-channel fluorimetry is described. It is shown that correction for the partial overlap of emission spectra can readily be introduced after a calibration procedure is performed. This method was applied to the investigation into regulation of palmitoylcarnitine oxidation. It was found that in the presence of rotenone, malonate and a redox buffer for the mitochondrial NAD-system, the beta-oxidation flux was sensitive to variations in redox state of respiratory chain electron carriers at low states of NAD reduction. Therefore, the concept of beta-oxidation control caused solely by the NAD redox state can no longer be sustained.
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PMID:Evaluation of electron-transfer flavoprotein and alpha-lipoamide dehydrogenase redox states by two-channel fluorimetry and its application to the investigation of beta-oxidation. 333


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