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Query: KEGG:D02011 (FAD)
 5,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of halothane, a potent and popular volatile anesthetic, on isolated rat liver mitochondria was examined. Halothane inhibited state 3 and dinitrophenol-induced uncoupled respiration with NAD(+)-linked substrates, but not with FAD-linked substrates, and did not affect the oxidation-reduction state of mitochondrial cytochromes. Moreover, halothane increased state 4 respiration and ATPase activity and decreased the extra-mitochrondrial pH change coupled to ATP synthesis. These results indicate that halothane impairs mitochondrial ATP production by interfering with both the electron transport from NAD+ to FAD and the coupling of oxidative phosphorylation. Halothane only slightly affected the membrane potential, which is commonly dissipated by typical classical uncouplers. Moreover, halothane inhibited both ATP-driven and respiration-driven Ca2+ accumulation in mitochondria and stimulated Ca2+ release from mitochondrial stores at concentrations higher than those at which it inhibited ATP production. These findings indicate that the uncoupling action of halothane is not classical. During halothane anesthesia, these mitochondrial abnormalities may contribute to hepatocyte dysfunctions.
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PMID:Halothane impairs the bioenergetic functions of isolated rat liver mitochondria. 216 74

Bacterial plasmids have genes that confer highly specific resistances to As, Bi, Cd, Cu, Cr, Hg, Pb, Te, Zn, and other toxic heavy metals. For each toxic cation or anion, generally a different resistance system exists, and these systems may be "linked" together on multiple resistance plasmids. For Cd2+, AsO2-, AsO4(3)-, Hg2+, and organomercurials, DNA sequence analysis has supplemented direct physiological and biochemical experiments to produce sophisticated understanding. The cadA ATPase of S. aureus plasmids is a 727 amino acid membrane ATPase that pumps Cd2+ from the cells as rapidly as it is accumulated. This polypeptide is related by sequence to other cation translocating ATPases, including the membrane K+ ATPases of Escherichia coli and Streptococcus faecalis, the H+ ATPases of yeast and Neurospora, the Na+/K+ ATPases of vertebrate animals, and the Ca2+ ATPases of rabbit muscle. The conserved residues include the aspartyl residue that is phosphorylated, the lysine involved in ATP binding, and the proline within a membrane translocating region. The arsenate and arsenite translocating ATPase consists of 3 polypeptides (from DNA sequence analysis), including a recognizable ATP binding protein (arsA), an integral membrane protein (arsB gene), and a substrate specificity subunit (arsC gene). Inorganic mercury and organomercurial degradation is carried out by a series of about 6 polypeptides, including 2 soluble intracellular enzymes (organomercurial lyase and mercuric reductase). The latter is related by sequence and function to glutathione reductase and lipoamide dehydrogenase of prokaryotes and eukaryotes. These enzymes are dimeric, FAD-containing, NAD(P)H-dependent oxidoreductases. Other recognizable polypeptides in the mer system include a DNA-binding regulatory protein from the merR gene and a Hg2+ transport system consisting of a periplasmic Hg2(+)-binding protein (merP gene) and a membrane protein (merT gene) in gram negative systems.
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PMID:DNA sequence analysis of bacterial toxic heavy metal resistances. 248 81

The characteristics of hydroperoxide activation of 5-lipoxygenase were examined in the high speed supernatant fraction prepared from rat polymorphonuclear leukocytes. Stimulation of 5-lipoxygenase activity by the 5-hydroperoxyeicosatetraenoic acid (5-HPETE) reaction product was strongly dependent on the presence of thiol compounds. Various reducing agents such as mercaptoethanol and glutathione (0.5-2 mM) inhibited the reaction and increased the concentrations of 5-HPETE (1-10 microM) necessary to achieve maximal arachidonic acid oxidation. The requirement for 5-HPETE was not specific and could be replaced by H2O2 (10 microM) but not by the 5-hydroxyeicosatetraenoic acid (5-HETE) analogue. Furthermore, gel filtration chromatography of the soluble extract from leukocytes resolved different fractions which can increase the hydroperoxide dependence or fully replace the stimulation by 5-HPETE. Maximal activity of the 5-HPETE-stimulated reaction required Ca2+ ions (0.2-1 mM) and ATP with the elimination of the HPETE requirement at high ATP concentrations (2-4 mM). In addition, NADPH (1-2 mM), FAD (1 mM), Fe2+ ions (20-100 microM) and chelated Fe3+ (0.1 mM-EDTA/0.1 mM-FeCl3) all markedly increased product formation by 5-lipoxygenase whereas NADH (1 mM) was inhibitory and Fe3+ (20-100 microM) alone had no effect on the reaction. The stimulation by Fe2+ ions and NADPH was also observed under various conditions which increase the hydroperoxide dependence such as pretreatment of the enzyme preparation with glutathione peroxidase or chemical reduction with 0.015% NaBH4. These results provide evidence for an hydroperoxide activation of 5-lipoxygenase which is not product-specific and is modulated by thiol levels and several soluble components of the leukocytes. They also indicate that stimulation of 5-lipoxygenase activity can contribute to increase lipid peroxidation in iron and nucleotide-promoted reactions.
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PMID:Stimulation of 5-lipoxygenase activity under conditions which promote lipid peroxidation. 251 7

Substrate specificity and product inhibition have been evaluated by using purified rat liver FAD synthetase (ATP:FMN adenylyltransferase, EC 2.7.7.2), obtained by an improved purification protocol with optimized flavin affinity chromatography. FMN analogues studied fall into three general classifications: those with substitution on the pyrimidinoid ring and nitrogen replacement, those with substitution on the benzenoid ring, and those with N(10) side chain modifications. Substitutions on the pyrimidinoid ring and replacement of nitrogens have the greatest influence on binding to enzyme and FAD formation. When the hydrogen-bonding capacity of the NH group at position 3 is blocked or removed by substitution, such FMN analogues do not act as substrates or inhibitors of the enzyme. Substitutions on the benzenoid ring by small groups seem to be tolerated, while larger groups inhibit binding. Length of the N(10) side chain is optimal with five carbons and has greatest affinity for the natural ribityl side chain. Affinity matrices show similar binding characteristics in that the N(3)-(carboxymethyl)riboflavin-agarose does not bind enzyme, while agaroses linked to the flavin N(10) side chain provide varying degrees of purification. The C = O group at position 2, the NH group at position 3, and a five-carbon side chain at the N(10) position seem to be most crucial for flavin substrate binding to enzyme. Nucleoside triphosphates other than ATP do not act as substrates or inhibitors when sufficient Mg2+ is present. Products of the reaction, FAD and PPi, act as inhibitors against both ATP and FMN.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Substrate specificity and variables affecting efficiency of mammalian flavin adenine dinucleotide synthetase. 255 3

Hyper- but not normoglycemic cats exposed to 8 min of anoxia show neurologic signs (fasciculations, myoclonic jerks, seizures) that develop after a symptom-free period. We examined brain mitochondrial function and metabolite concentrations at 0, 1, 3, and 5 h following exposure to anoxia, to correlate biochemical findings with the presence ("symptomatic") or absence ("presymptomatic") of neurologic signs. Brain mitochondria isolated postexposure only from symptomatic cats showed markedly decreased (-50%), state 3 (ADP-stimulated), and uncoupler-stimulated respiration rates with NAD- and FAD-linked substrates. Respiratory control and ADP/oxygen (ADP/O) ratios remained unchanged, indicating, respectively, that coupling and efficiency of ATP synthesis were preserved. Thus, inhibition of electron transport chain function, not phosphorylative activity, may be rate limiting for respiration. During anoxia, hyperglycemic cats showed higher brain lactate levels (26 versus 20 mumol/g), but similar ATP and phosphocreatine concentrations, compared with normoglycemic cats. After exposure, in all animals lactate and phosphocreatine were restored to control levels, whereas ATP remained at 85%. Cats that became symptomatic demonstrated four- to sixfold increases in lactate and 50% reductions in phosphocreatine. At 3 and 5 h postexposure, symptomatic animals showed significant reductions in ATP concentrations. We conclude that although initially asymptomatic, hyperglycemic cats exposed to anoxia undergo a neurologic deterioration over several hours following reoxygenation that is correlated with inhibition of mitochondrial respiration, increases in tissue lactate, and decreases in energy state.
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PMID:Delayed neurologic deterioration following anoxia: brain mitochondrial and metabolic correlates. 256 72

The respiratory chain of a marine bacterium, Vibrio alginolyticus, required Na+ for maximum activity, and the site of Na+ -dependent activation was localized on the NADH-quinone reductase segment. The Na+ -dependent NADH-quinone reductase extruded Na+ as a direct result of redox reaction. It was composed of three subunits, alpha, beta, and gamma, with apparent Mr of 52, 46, and 32 KDa, respectively. The reduction of ubiquinone-1 to ubiquinol proceeded via ubisemiquinone radicals. The former reaction was catalyzed by the FAD-containing beta subunit. This reaction showed no specific requirement for Na+. For the formation of ubiquinol, the presence of the gamma subunit and the FMN-containing alpha subunit was essential. The latter reaction specifically required Na+ for activity and was strongly inhibited by 2-n-heptyl-4-hydroxyquinoline N-oxide. It was assigned to the coupling site for Na+ transport. The mode of energy coupling of redox-driven Na+ pump was compared with those of decarboxylase- and ATP-driven Na+ pumps found in other bacteria.
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PMID:Sodium-transport NADH-quinone reductase of a marine Vibrio alginolyticus. 268 59

The NADPH-dependent superoxide production induced by sodium dodecyl sulfate (SDS) in the sonicates of unstimulated pig neutrophils required both membrane fraction and two components of cytosol fraction. The potency of the cytosol fraction in the activation of the superoxide production could be reconstituted dose dependently by mixing two protein components with relative molecular masses of 300 kDa and 50 kDa. Another low-molecular-mass component (1.3 kDa) could substitute the 50-kDa component. In the cell-free system consisting of the 300- and 50-kDa components and the membrane fraction, the superoxide production was markedly enhanced by FAD with a required concentration for half-maximal effect of 0.16 microM and inhibited by divalent cations such as Ca2+, Ba2+, Co2+, Zn2+ and Mn2+ and not Mg2+. ATP was not necessary for the activation, indicating that protein kinases such as protein kinase C are not involved in the SDS-dependent activation of NADPH oxidase. The NADPH oxidase activated by SDS in the cell-free system was recovered in the membrane fraction, and the superoxide formation by the SDS-activated membrane exhibited a Km value for NADPH of 46 microM and optimum pH at 7.0. The formation did not require the addition of SDS and FAD to the reaction mixture and was scarcely inhibited by the divalent cations.
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PMID:Characterization of the NADPH-dependent superoxide production activated by sodium dodecyl sulfate in a cell-free system of pig neutrophils. 282 May 10

The cytosolic component of macrophage-derived superoxide generating NADPH oxidase was partially purified by affinity chromatography on 2',5'-ADP-agarose. Elution was nonspecific by elevated phosphate molarity. A single step attains at least 40-fold enrichment of specific activity, the recovery being over 20%. Elution with various ligands in the concentration range 2-3.5 mM was also tested. The most effective ligands were: ATP, dATP, GTP, NADPH and 2',5'-ADP. Ineffective were AMP, 2'-AMP, FMN, FAD and NADH. ADP was of medium potency. On the basis of the above and other results, we infer that the molecule (or complex) purified by us may contain the enzymatic NADPH binding site. This component is fully retained by a 100 kDa cutoff membrane and is labile at room temperature, the lability being cancelled by 2-mercaptoethanol.
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PMID:Macrophage-derived superoxide-generating NADPH oxidase in an amphiphile-activated, cell-free system; partial purification of the cytosolic component and evidence that it may contain the NADPH binding site. 282 78

An enzyme with FAD pyrophosphatase activity was extracted from human placental syncytiotrophoblast microvilli and purified to near-homogeneity. The enzyme has been identified as 5'-nucleotidase by several criteria. Throughout purification, parallel increases in the specific activities of FAD pyrophosphatase and AMP phosphatase were observed. The enzyme was a glycoprotein with a subunit molecular weight of 74,000. EDTA treatment resulted in a marked decline in both activities, and restoration of FAD pyrophosphatase activity but not 5'-nucleotidase activity was accomplished by the addition of Co2+ or, to a lesser extent, Mn2+. The substrate specificity of the 5'-nucleotidase activity that we observed agreed closely with the results of others. The pyrophosphatase activity was relatively specific for FAD. ADP, ATP, NAD(H), and FMN were not hydrolyzed, and ADP strongly inhibited both activities. For FAD pyrophosphatase activity, a Km of 1.2 x 10(-5) M and a Vmax of 1.1 mumol/min/mg protein were determined in assays performed in the presence of Co2+. In the absence of added Co2+, the Vmax declined but the Km was unchanged. For 5'-nucleotidase (AMP as substrate) the Km was 4.1 x 10(-5) M and the Vmax 109 mumol/min/mg protein. Hydrolysis of FMN to riboflavin was observed in partially purified detergent extracts of microvilli that contained alkaline phosphatase activity and lacked FAD pyrophosphatase and 5'-nucleotidase activity. The presence of both FAD pyrophosphatase and FMN phosphatase activities in syncytiotrophoblast microvilli supports the view that the placental uptake of vitamin B2 involves the hydrolysis of FAD and FMN to riboflavin which is then absorbed, a sequence postulated for intestinal absorption and liver uptake.
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PMID:5'-Nucleotidase of human placental trophoblastic microvilli possesses cobalt-stimulated FAD pyrophosphatase activity. 284 89

In this study, we have identified a delta 24-unsaturated intermediate involved in the conversion of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid to cholic acid by the peroxisomal fraction of rat liver. An accumulation of this intermediate was observed when NAD+ was omitted from the reaction mixture. The intermediate was isolated by reversed-phase high-pressure liquid chromatography and identified by combined gas-liquid chromatography-mass spectrometry. The peroxisomal fraction was able to catalyze the conversion of the delta 24-unsaturated intermediate to cholic acid in the presence of CoA, ATP, Mg2+ and NAD+. The identification of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholest-24-enoic acid in cholic acid formation supports the proposed reaction mechanism in which the side-chain cleavage of C27-steroids is similar to that of peroxisomal beta-oxidation of fatty acids. This involves an FAD-dependent oxidase acting on 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoyl-CoA.
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PMID:Identification of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholest-24-enoic acid as an intermediate in the peroxisomal conversion of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid to cholic acid. 293 Jul 67


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