Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:EXPT02288 (NADH)
 21,914 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Washed cells of Bacteroides melaninogenicus are unable to incorporate the sphingolipid precursor 3-ketodihydrosphingosine (3KDS) or dihydrosphingosine into the complete sphingolipids ceramide phosphorylethanolamine (CPE) and ceramide phosphorylglycerol (CPG), whereas growing cultures are able to do so. This result suggested that an energy source was required by washed cells to initiate the incorporation of 3KDS. Investigation of a number of energy sources for B. melaninogenicus showed that glutamine was active in driving the incorporation of 3KDS. This system shows saturation kinetics. Besides glutamine, only asparagine and reduced nicotinamide adenine dinucleotide (NADH) are effective; glutamate and other compounds are inactive. The glutamine-driven system is sensitive to 2,4-dinitrophenol, azide, N,N'- dicyclohexylcarbodiimide, and carbonyl cyanide m-chlorophenylhydrazone. Asparagine plus NADH shows a synergistic effect in stimulating the incorporation of 3KDS into CPE and CPG in washed cells. However, glutamine plus NADH and glutamine plus asparagine show no such synergy. The cytochrome-free mutant of B. melaninogenicus, strain S, incorporates 3KDS in a manner similar to the parent strain when glutamine is used to drive the reaction; NADH or asparagine, however, are ineffective when used with strain S. Vitamin K-depleted cells of B. melaninogenicus are similar to vitamin K-grown cells, when glutamine or NADH is used to drive the 3KDS incorporation. Glutamine and NADH are also effective in stimulating the incorporation of palmitate and acetate by washed cells of B, melaninogenicus. Increased incorporation of these fatty acids into CPE, CPG, 3KDS, and other phospholipids is significantly increased by the presence of glutamine or NADH. Thus, energization of the membrane of B. melaninogenicus by glutamine or the electron transport system by NADH or asparagine is required for sphingolipid and other phospholipid synthesis. The relationship of this energization to possible transport of sphingolipid precursors is discussed.
 ...
PMID:Energy-dependent incorporation of sphingolipid precursors and fatty acids in Bacteriodes melaninogenicus. 1 84

Studies were carried out on the delta 5-desaturation reaction in ergosterol biosynthesis with a particulate fraction of cell-free extract of yeast. A reduced pyridine nucleotide coenzyme and molecular oxygen were required for the reaction. It was shown that the enzyme activity is located in a fraction corresponding to microsomes. The reaction was inhibited by KCN, but not by CO. Menadione and potassium ferricyanide inhibited the NADPH- and NADH-dependent reactions, respectively, and cytochrome c inhibited both of them. These results suggested an involvement in delta 5-desaturation of a mixed function oxidase system resembling that for the fatty acyl-CoA desaturation reaction.
 ...
PMID:Studies on the delta 5-desaturation in ergosterol biosynthesis in yeast. 3

Cytochrome-deficient cells of a strain of Escherichia coli lacking 5-amino-levulinate synthetase have been used to study proton translocation associated with the reduced nicotinamide adenine dinucleotide (NADH) dehydrogenase region of the electron transport chain. Menadione was used as electron acceptor, and mannitol was used as the substrate for the generation of intracellular NADH. The effects of iron deficiency on NADH- and D-lactate-menadione reductase activities were studied in iron-deficient cells of a mutant strain unable to synthesize the iron chelator enterochelin; both activities were reduced. The NADH- menadione reductase activity in cytochrome-deficient cells was associated with proton translocation and could be coupled to the uptake of proline. However proton translocation associated with the NADH-menadione reductase activity was prevented by a mutation in an unc gene. It was concluded that there is no proton translocation associated with the NADH-dehydrogenase region of the electron transport chain in E. coli and that the proton translocation obtained with mannitol as substrate is due to the activity of membrane-bound adenosine triphosphatase.
 ...
PMID:Proton translocation in cytochrome-deficient mutants of Escherichia coli. 15 8

Vitamin K is a component of a membrane-bound enzyme complex which catalyzes the posttranslational carboxylation of peptide-bound glutamate to form the gamma-carboxyglutamate (Gla) residues of prothrombin. The reaction requires reduced vitamin K, bicarbonate, oxygen, and a carboxylase, and does not require ATP. In a Triton X-100 solubilized carboxylase system, it was found that the naphthoquinone ring structure is essential for activity, as is the 2-methyl group. Menaquinone homologs from MK-1 to MK-4 all had carboxylase activity, whereas menadione was inactive. However, dithiothreitol and other thiols form thioethers with menadione, which restores considerable carboxylation activity to the provitamin. Hydrogenation of the beta-gamma double bond in phylloquinone reduced its activity only slightly. The active species of "CO2" utilized in this carboxylation is CO2 and not bicarbonate. Ribosomes contain Gla residues and are labeled with CO2 when whole microsomes are incubated with CO2 in the presence of NADH and vitamin K. About 25% of the activity is releasable with puromycin, suggesting that Gla residues are formed on both the nascent chains and the structural proteins of ribosomes. The deoxycholate-solubilized carboxylase system can be dialyzed to yield membranous vesicles with enhanced carboxylase activity. The warfarin-binding protein from normal rats, but not that from warfarin-resistant rats, further enhances the carboxylase activity of these reformed vesicles.
 ...
PMID:Nature of the vitamin K-dependent CO2 fixation in microsomal membranes. 70 Jan 70

Vitamin K participates in the post-translational carboxylation of peptide-bound glutamate to form the gamma-carboxy-glutamate residues of prothrombin. The reaction requires reduced vitamin K, bicarbonate, oxygen, and a membrane-bound carboxylase. The active species of "CO2," i.e. CO2 or HCO3-, utilized in this carboxylation was determined by the low temperature method of Filmer and Cooper ((1970) J. Theor. Biol. 29, 131-145), taking advantage of the fact that menaquinone-2, in contrast to phylloquinone, is very active at 10 degrees. Microsomes from livers of vitamin K-deficient rats, were incubated in the presence of cycloheximide, avidin, NADH, menaquinone-2, 1 mM acetazolamide (to inhibit carbonic anhydrase), and either 14CO2 or H14CO3-. At 1-min intervals aliquots were removed from the reaction mixture. gamma-Carboxyglutamate was isolated from these samples by ion exchange chromatography after alkaline hydrolysis. After 1 min the incorporation of 14CO2 into gamma-carboxyglutamate was 8 to 10 times as great as that found with H14CO3-. When the carbonic anhydrase inhibitor was omited (with or without addition of exogenous carbonic anhydrase) the two incorporation curves approximated each other at a rate near that exhibited by bicarbonate alone. Similar results were obtained in a microsomal carboxylase system solubilized with Triton X-100. It is concluded that CO2 is the active species of "CO2" initially participating in the vitamin K-dependent carboxylation of preprothrombin and that neither ATP nor biotin is required for the reaction.
 ...
PMID:Vitamin K-dependent carboxylation of peptide-bound glutamate. The active species of "CO2" utilized by the membrane-bound preprothrombin carboxylase. 91 35

Vitamin K is required for an enzymatic carboxylation of glutamyl residues in a microsomal protein precursor of plasma prothrombin to form gamma-carboxyglutamic acid. The enzyme system (carboxylase) which catalyzes this reaction has now been solubilized by extraction of the microsomes with Triton X-100 and has been shown to fix H14CO3- as gamma-carboxyglutamic acid residues in biologically active prothrombin. Enzyme activity requires O2 and vitamin K hydroquinone or vitamin K + NADH. Unlike the microsomal-bound carboxylase, soluble carboxylase activity is independent of either ATP or Mg2+ addition and is unaffected by either the ATP analog, adenyl-5'-yl imidodiphosphate (AMP-P(NH)P, or EDTA. These observations suggest that the energy required to drive the carboxylation reaction is derived from the oxidation of the reduced form of vitamin K. Although the membrane-bound carboxylase is inhibited by Warfarin, this anticoagulant is ineffective as an inhibitor of the soluble enzyme. A second anticoagulant, 2-chloro-3-phytyl-1,4-natpthoquinone (chloro-K), differs from Warfarin in that it effectively inhibits both the membrane-bound and soluble carboxylases.
 ...
PMID:Vitamin K-dependent carboxylase. Solubilization and properties. 97 68

Oxidative metabolism in whole cells of Escherichia coli strain 82/r was inhibited by d-camphor when glucose, pyruvate, or succinate was used as substrate. Inhibition was not due to lower surface tension in d-camphor-treated cell suspensions nor was it a function of cell permeability. Succinic, lactic, and NADH-oxidase activities were inhibited in alumina powder cell-free extracts (80 mug of protein/ml) by d-camphor (1100 mug/ml). NADH: and succinic: DCPIP oxidoreductase enzymes were unaffected by d-camphor. Menadione (vitamin K3) restored succinic, lactic, and NADH-oxidase activities in d-camphor-inhibited cell-free extracts. Concentrations of menadione used to restore succinic and NADH oxidase activities were not stimulatory in non-camphor-treated extracts. Succinic oxidase activity in d-camphor-inhibited cell-free extracts was also restored by ubiquinone (Q6) but not by vitamin K1. These results are interpreted to indicate that d-camphor may affect quinone function in E. coli.
 ...
PMID:Inhibition of oxidative metabolism in Escherichia coli by d-camphor and restoration of oxidase activity by quinones. 110 72

1. In both guinea-pig and rat heart, mitochondrial NADH-ubiquinone-reductase and soluble DT-diaphorase accounted for 49-50% and 48-50% of menadione metabolism, respectively. Microsomal NADPH-cytochrome P450-reductase was responsible for less than 1% of menadione reduction. 2. Menadione was a high-affinity substrate for all reductases (Km values from 1 to 10 microM). 3. Marked amounts of O2-. (superoxide anion) were generated as a consequence of cardiac metabolism of menadione. 4. Menadione-induced O2-. generation was about 3-fold higher in guinea-pig than in rat heart. 5. All results were compared with data obtained on guinea-pig and rat liver.
 ...
PMID:One- and two-electron reduction of menadione in guinea-pig and rat cardiac tissue. 139 83

NADH was found previously to catalyze the reduction of various ferric complexes and to promote the generation of reactive oxygen species by rat liver microsomes. Experiments were conducted to evaluate the ability of NADH to interact with ferric complexes and redox cycling agents to catalyze microsomal generation of potent oxidizing species. In the presence of iron, the addition of menadione increased NADPH- and NADH-dependent oxidation of hydroxyl radical (.OH) scavenging agents; effective iron complexes included ferric-EDTA, -diethylenetriamine pentaacetic acid, -ATP, -citrate, and ferric ammonium sulfate. The stimulation produced by menadione was sensitive to catalase and to competitive .OH scavengers but not to superoxide dismutase. Paraquat, irrespective of the iron catalyst, did not increase significantly the NADH-dependent oxidation of .OH scavengers under conditions in which the NADPH-dependent reaction was increased. Menadione promoted H2O2 production with either NADH or NADPH; paraquat was stimulatory only with NADPH. Stimulation of H2O2 generation appears to play a major role in the increased production of .OH-like species. Menadione inhibited NADH-dependent microsomal lipid peroxidation, whereas paraquat produced a 2-fold increase. Neither the control nor the paraquat-enhanced rates of lipid peroxidation were sensitive to catalase, superoxide dismutase, or dimethyl sulfoxide. Although the NADPH-dependent microsomal system shows greater reactivity and affinity for interacting with redox cycling agents, the capability of NADH to promote menadione-catalyzed generation of .OH-like species and H2O2 or paraquat-mediated lipid peroxidation may also contribute to the overall toxicity of these agents in biological systems. This may be especially significant under conditions in which the production of NADH is increased, e.g. during ethanol oxidation by the liver.
 ...
PMID:NADH-dependent generation of reactive oxygen species by microsomes in the presence of iron and redox cycling agents. 165 Feb 15

Menadione (2-methyl-1,4-naphthoquinone) was used as a model compound to test the hypothesis that thioether conjugates of quinones can be toxic to tissues associated with their elimination through a mechanism involving oxidative stress. Unlike menadione, the glutathione (2-methyl-3-(glutathion-S-yl)-1,4-naphthoquinone; MGNQ) and N-acetyl-L-cysteine (2-methyl-3-(N-acetylcysteine-S-yl)-1,4-naphthoquinone; M(NAC)NQ) thioether conjugates were not able to arylate protein thiols but were still able to redox cycle with cytochrome c reductase/NADH and rat kidney microsomes and mitochondria. Interestingly, menadione and M(NAC)NQ were equally toxic to isolated rat renal epithelial cells (IREC) while MGNQ was nontoxic. The toxicity of both menadione and M(NAC)NQ was preceded by a rapid depletion of soluble thiols and was associated with a depletion of soluble thiols and was associated with a depletion of protein thiols. Treatment of IREC with the glutathione reductase inhibitor, 1,3-bis(2-chloroethyl)-1-nitrosourea, potentiated the thiol depletion and toxicity observed with menadione and M(NAC)NQ indicating the involvement of oxidative stress in this model of renal cell toxicity. The lack of MGNQ toxicity can be attributed to an intramolecular cyclization reaction which destroys the quinone nucleus and therefore eliminates its ability to redox cycle. These findings have important implications with regard to our understanding of the toxic potential of quinone thioether conjugates and of quinone toxicity in general.
 ...
PMID:The toxicity of menadione (2-methyl-1,4-naphthoquinone) and two thioether conjugates studied with isolated renal epithelial cells. 199 Sep 78


1 2 3 4 Next >>