Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dantrolene sodium is a medically important hydantoin derivative that interferes with release of Ca2+ from intracellular stores of skeletal muscle by an unknown mechanism. Identification of the molecular target of dantrolene would greatly aid in understanding both the mechanism of action of the drug and the dynamics of intracellular Ca2+ release in muscle. [3H]Azidodantrolene was designed and synthesized as a photoaffinity analogue in order to identify a putative dantrolene receptor in skeletal muscle. Introduction of 1 mole-atom of tritium into aldehyde 5b was required during radioligand synthesis in order to ensure high enough specific activity for detection of photo-cross-linked proteins by fluorographic methods. This was accomplished by reduction of ester 3 with custom synthesized, 100% tritium-labeled lithium triethylborotritide, followed by oxidation to 5b by manganese(IV) oxide. Compound 6b was demonstrated to be >/=95% tritium-labeled at the imine position by NMR spectroscopy, and the specific radioactivity of [3H]azidodantrolene sodium was empirically determined by HPLC and liquid scintillation counting to be 24.4 Ci/mmol, approximately 85% of theoretical maximum. [3H]Azidodantrolene was found to be pharmacologically active in ligand-receptor binding studies with skeletal muscle sarcoplasmic reticulum membranes. Photo-cross-linking experiments analyzed by SDS-PAGE and tritium fluorography have identified a approximately 160-kDa specifically labeled protein as the putative, intracellular, skeletal muscle dantrolene receptor. This photolabeled protein comigrates with a protein in Western blots immunologically cross-reactive to a polyclonal anti-rabbit skeletal muscle ryanodine receptor antibody. Thus, the putative dantrolene receptor may be related to the skeletal muscle ryanodine receptor.
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PMID:[3H]Azidodantrolene: synthesis and use in identification of a putative skeletal muscle dantrolene binding site in sarcoplasmic reticulum. 1035 95

In order to develop an intravenous formulation of all-trans-retinal (vitamin A aldehyde, VAA) for the treatment of night blindness, VAA and dipalmitoylphosphatidylcholine (DPPC) were sonicated and the dispersions in the VAA mole fraction range of 0.1-0.7 were stable at room temperature for 3 days. In order to clarify the dispersal mechanism, the dispersed particles were characterized and the interaction between VAA and DPPC was investigated using several physicochemical techniques. Dynamic light scattering measurements showed that the diameter of the dispersed particles was 50-70 nm. A limited amount of VAA is incorporated into DPPC bilayer membranes (approximately 5 mole%). The trapped aqueous volume inside the particles was determined fluorometrically using the aqueous space marker calcein and the volume in the VAA/DPPC particles was decreased remarkably with the addition of VAA into small unilamellar vesicles of DPPC. The decline in the fraction of vesicular particles was also confirmed by fluorescence quenching of N-dansylhexadecylamine in the DPPC membrane by the addition of the quencher CuSO(4). These results indicate that the excess VAA separated from the DPPC bilayers is stabilized as emulsion particles by the DPPC surface monolayer. The monolayer-bilayer equilibrium of VAA/DPPC mixtures was estimated by measurement of spreading and collapse pressures. The results showed that the coexistence of emulsion particles (surface monolayer of DPPC+core of VAA) with vesicular particles (bilayer) was critically important for the formation of the stably dispersed particles of the lipid mixture.
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PMID:Formation and structure of stably dispersed particles composed of retinal with dipalmitoylphosphatidylcholine: coexistence of emulsion particles with bilayer vesicles. 1047 32

The reaction with substrates and carbonyl reagents of native lentil Cu-amine oxidase and its modified forms, i.e. Cu-fully-depleted, Cu-half-reconstituted, Cu-fully-reconstituted, Co-substituted, Ni-substituted and Zn-substituted, has been studied. Upon removal of only one of the two Cu ions, the enzyme loses 50% of its enzymatic activity. Using several substrates, Co-substituted lentil amine oxidase is shown to be active but the k(c) value is different from that of native or Cu-fully-reconstituted enzyme, while K(m) is similar. On the other hand, the Ni- and Zn-substituted forms are catalytically inactive. Enzymatic activity measurements and optical spectroscopy show that only in the Co-substituted enzyme is the organic cofactor 6-hydroxydopa quinone reactive and the enzyme catalytically competent, although less efficient. The Co-substituted amine oxidase does not form the semiquinone radical as an intermediate of the catalytic reaction. While devoid or reduced of catalytic activity, all the enzyme preparations are still able to oxidise two moles of substrate and to release two moles of aldehyde per mole of dimeric enzyme. The results obtained show that although Co-substituted amine oxidase is catalytically competent, copper is essential for the catalytic mechanism.
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PMID:Effect of metal substitution in copper amine oxidase from lentil seedlings. 1055 Jun 90

Phenylacetaldehyde reductase (PAR) with a unique and wide substrate range from styrene-assimilating Corynebacterium sp. strain ST-10, which is a useful biocatalyst producing chiral alcohols, has been found to belong to a family of zinc-containing, long-chain alcohol dehydrogenases (ADHs) on the basis of the primary structure similarity. The enzyme contains 2 moles of zinc per mole of subunit. The amino acid residues assumed to be three catalytic and four structural zinc-binding ligands were characterized by site-directed mutagenesis, compared with other zinc-containing, long-chain ADHs. Sixteen PAR mutants gave measurable but rather low activities toward phenylacetaldehyde, n-hexyl aldehyde, and 2-heptanone, although they maintained the activities of 8 to 16% of that of wild-type PAR for an acetophenone substrate except that the D153N mutant showed quite low activity. The results suggested that the seven residues present in PAR were probably zinc-binding ligands, and mutation in these residues caused a change in activities for some substrates.
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PMID:Site-directed mutagenesis of two zinc-binding centers of the NADH-dependent phenylacetaldehyde reductase from styrene-assimilating Corynebacterium sp. strain ST-10. 1066 54

Sugars and amino acids were removed from potato slices by soaking in water and ethanol. They were then infused with various combinations of sugars (glucose and/or fructose) and amino acids (asparagine, glutamine, leucine, isoleucine, phenylalanine, and/or methionine) and fried. Volatile compounds were trapped onto Tenax prior to gas chromatography-mass spectrometry. Relative amounts of compounds (relative to the internal standard) and relative yields (per mole of amino acid infused into the slices) were determined. Amounts of 10 pyrazines, 4 Strecker aldehydes, and 4 other compounds were monitored. Relative amounts and relative yields of compounds varied according to the composition of the system. For the single amino acid-glucose systems, leucine gave the highest relative amount and relative yield of its Strecker aldehyde. Asparagine and phenylalanine gave the highest total relative amount and total relative yield, respectively, of pyrazines. In the system containing all of the amino acids and glucose, the relative amount of 3-methylbutanal was higher, whereas the amounts of the other monitored Strecker aldehydes were lower. Most of the relative amounts of individual pyrazines were lower compared to the glucose-asparagine system, whereas the total relative yield of pyrazines was lower, compared to all of the single amino acid-glucose mixtures. Addition of fructose to the mixed amino acid-glucose model system generated Strecker aldehydes and pyrazines in ratios that were more similar to those of untreated potato chips than to those from the same system but without fructose. Both the sugars and the amino acids present in potato are crucial to the development of flavor compounds in fried potato slices.
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PMID:Formation of Strecker aldehydes and pyrazines in a fried potato model system. 1151 84

This paper describes a study of oxidation of diethylene glycol (DEG) by ozone and modified Fenton process (hydrogen peroxide and ferric salt mixture) in aqueous solution. Both oxidation processes were able to oxidize relatively high concentrations of DEG effectively. DEG reacted primarily through hydroxyl radical produced by decomposition of ozone, and about 3 mol of ozone were consumed per mole of DEG removed during the process. For modified Fenton oxidation, stepwise addition of hydrogen peroxide (H2O2) and ferric salt (Fe(III)) resulted in much higher removal of DEG than one-time pulse addition of the chemicals. The extent of DEG removal increased with increasing concentrations of both H2O2 and Fe(III). Oxidant consumption per mole of DEG oxidized was one order of magnitude higher for hydrogen peroxide than those observed for ozone. Overall, ozonation produced higher concentrations of aldehydes, and modified Fenton treatment produced higher concentrations of carboxylic acids for the same levels of DEG oxidation. The major products of ozonation were glycolaldehyde, glyoxal, formaldehyde, acetaldehyde, and acetic, formic, pyruvic, oxalic and glyoxalic acids. The major products of modified Fenton oxidation were formaldehyde, and formic and acetic acids.
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PMID:Oxidation of diethylene glycol with ozone and modified Fenton processes. 1199 50

Formaldehyde, acetaldehyde, ozone and nitrogen dioxide in ambient air are simultaneously collected on silica gel cartridges coated with 1-methyl-1-(2,4-dinitrophenyl)hydrazine (MDNPH), where the two aldehydes are derivatized to their respective hydrazones, while the two oxidants are converted into N-methyl-2,4-dinitroaniline (MDNA). The three products are then separated and quantified by HPLC with UV detection at 360 nm. The stoichiometric factors of the MDNPH reactions with O3 and NO2 in laboratory tests correspond to 2.0 +/- 0.1 moles of MDNA per mole of O(x) (O3 + NO2). The limits of detection (LOD) are 0.7 ppbv HCHO, 0.8 ppbv CH3CHO and 1.6 ppbv O(x) for 30 L (1 h) air sampled. The sampling performance is insensitive to relative humidities encountered in real atmospheres. When compared with Sep-Pak DNPH silica cartridges as well as with ozone photometric and nitrogen dioxide chemiluminescent analyzers, the proposed chromatographic method demonstrates a very good accuracy (12% for HCHO, 14% for CH3CHO and 7% for O(x), on the average) under field sampling conditions at concentrations lower than 3 and 1 ppbv, for HCHO and CH3CHO, respectively and ranging from 28 to 62 ppbv for O(x).
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PMID:Simultaneous determination of HCHO, CH3CHO and O(x) in ambient air by hydrazine reagent and hplc. 1265 May 83

1. The enzyme which splits threonine to acetaldehyde and glycine has been partially purified from rat liver (five- to sixfold purification) and the name threonine aldolase proposed for it. 2. The general properties of threonine aldolase have been studied. The enzyme is unstable to a pH below 5. The pH optimum of the enzyme reaction is at 7.5-7.7. The initial rate of production of acetaldehyde is proportional to the enzyme concentration, and when the enzyme concentration is constant, the production of acetaldehyde is proportional to the time, provided that the substrate is in excess. The enzyme is inhibited by the carbonyl group reagent, hydroxylamine. Attempts to demonstrate that pyridoxal phosphate is a cofactor were unsuccessful. 3. The enzyme splits only L-allothreonine and L-threonine and is inactive against the D-forms of these amino acids. 4. The enzyme reaction on DL-allothreonine follows first order kinetics. From the first order velocity constants and the initial rates of the rates of the reaction at various substrate concentrations the Michaelis constant, Ks, for this substrate has been evaluated. Michaelis constants have also been determined for threonine. 5. The optimum temperature for the enzymatic breakdown of DL-allothreonine at pH 7.65 was found to be 50 degrees C. in phosphate buffer and 48 degrees C. in tris-maleate buffer. The rate of thermal inactivation of the enzyme threonine aldolase obeys a first order reaction. The heat of thermal inactivation was calculated by the aid of the van't Hoff-Arrhenius equation to be 43,000 cal. per mole for the temperature range 41.2-46.6 degrees C. 6. Equivalent amounts of acetaldehyde and glycine were formed from DL-allothreonine and the enzymatic breakdown of DL-allothreonine was found to be irreversible.
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PMID:Enzymatic breakdown of threonine by threonine aldolase. 1321 95

Acrolein (ACR), the carbonyl toxin produced by lipid peroxidation, is significantly increased in Alzheimer's disease brain. Since ACR is one of the most reactive and neurotoxic aldehydes, and human brain contains both carnosine (beta-alanine-L-histidine) and homocarnosine (gamma-aminobutyryl-L-histidine), the aim of this work was first to evaluate the quenching ability of the two peptides towards ACR and then to characterize their reaction products by electrospray ionization tandem mass spectrometry (ESI-MS/MS; infusion experiments; positive-ion mode). The reaction progress of ACR with carnosine or homocarnosine was studied in phosphate buffer, by monitoring ACR consumption (by reverse-phase LC) and formation of the reaction products by ESI-MS/MS at different incubation times. N-Acetylcarnosine was used as reference compound to identify the sites of reaction. Both the dipeptides were able to quench ACR by almost 60% at 1 h and by more than 85% after 3 h incubation. Different reaction products between ACR and carnosine/homocarnosine were detected after 3 and 24 h, to indicate a complex reaction pathway involving sequential addition of 1, 2 and 3 moles of ACR/mole of the dipeptide to both the beta-alanine and histidine residues. The ESI mass spectra of ACR/carnosine reaction mixtures indicate formation of several molecular species, among which the predominant are: (a) the 14-membered macrocyclic derivatives, deriving from the formation of the iminic bond between the terminal amino group followed by intramolecular Michael addition of the C(3) of the ACR moiety to histidine; (b) the N(beta)-(3-formyl-3,4-dehydropiperidino) derivatives arising from the Michael addition of two acrolein molecules to the amino group of beta-alanine, followed by an aldol condensation and dehydration.The reaction of homocarnosine with ACR follows the same pathway, giving rise to the formation of homologous adducts. The results of this study shed light on the mechanism, until now never demonstrated, through which carnosine and homocarnosine detoxify the highly reactive aldehyde acrolein in a buffer system, and represent the starting point for further studies aimed at elucidating the biological role of these dipeptides in brain.
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PMID:Acrolein-sequestering ability of endogenous dipeptides: characterization of carnosine and homocarnosine/acrolein adducts by electrospray ionization tandem mass spectrometry. 1450 28

Organic nitrites, such as i-amyl nitrite (IAN), are nitrovasodilator drugs used both clinically and recreationally. Nitrites are also chemically reasonable biological products of NO metabolism, in particular in both inhibition of lipid peroxidation by NO and induction of lipid peroxidation by peroxynitrite and NO2. Nitrites are also potential products of biomolecule nitrosation and intermediates in biotransformation of nitrate vasodilators. Although mechanisms can be drawn for both prooxidant and antioxidant activity, IAN has been observed to inhibit lipid peroxidation in a variety of systems. To test if the antioxidant activity of nitrites results from NO release alone, inhibition of lipid peroxidation was studied for four organic nitrites and four NO donor NONOates. Iron-induced lipid peroxidation in synaptosomal tissue homogenates and azo compound-initiated lipid peroxidation in liposomes and linoleic acid SDS comicelles were examined. Lipid peroxidation was quantified by TBARS and oxygen uptake analysis. A good correlation of rate of NO release with IC50 for inhibition of lipid peroxidation was observed for the NONOates, compatible with lipid radical chain termination by NO, for which a chain termination stoichiometry of 0.4-0.5 mol of lipid peroxyl radicals per mole of NO was determined. In neutral aqueous solution, nitrites also spontaneously released NO as measured by chemiluminescence; however, no correlation was observed between the rate constants of NO release for the nitrites and their inhibitor potency toward lipid peroxidation. Long chain nitrites were seen to be relatively good inhibitors of lipid peroxidation by mechanisms that must involve factors in addition to simple homolysis to release NO. Evidence for direct alpha-hydrogen atom abstraction from the nitrite by peroxyl radicals was obtained by analysis of aldehyde products and supported by MO calculations. The data suggest that lipid nitrites formed as NO chain termination products have the capacity to further inhibit lipid peroxidation and to release NO.
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PMID:Organic nitrites and NO: inhibition of lipid peroxidation and radical reactions. 1496 6


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