Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:61191-21-7 (2-butanone)
 604 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

NAD-dependent alcohol dehydrogenase from the methanol-grown Methylcoccus sp. CRL M1 (type I membrane), Methylosinus trichosporium OB3b (type II membrane), Methylobacterium organophillum CRL 26 (type II membrane, facultative methylotroph). Pseudomonas sp. ATCC 21439, and Pichia pastoris Y-55 are secondary-alcohol-specific and that from P. pastoris Y-7556 is not. This novel secondary-alcohol-specific alcohol dehydrogenase (secondary-alcohol dehydrogenase) has been purified from methanol-grown Pseudomonas sp. ATCC 21439. Secondary-alcohol dehydrogenase shows a single protein band on acrylamide gel electrophoresis and has a molecular weight of 95000. It consists of two subunits of Mr 48000 daltons and two atoms of zinc per molecule of enzyme protein. It oxidizes secondary alcohols, notably 2-propanol and 2-butanol. Primary alcohols are not oxidized. The pH and temperature optima for secondary-alcohol dehydrogenase are 8--9, and 30--35 degrees C, respectively. The activation energy calculated is 82.8 kJ. Secondary-alcohol dehydrogenase also catalyzes the reduction of methyl ketones to their corresponding 2-alcohols in the presence of NADH (a reverse reaction). The Km values at 25 degrees C in the forward reaction for 2-butanol, (2R)-(-)-butan-2-ol, and NAD, and in the reverse reaction for 2-butanone and NADH are 2.5 x 10(-4) M, 1.6 x 10(-4) M, 11 x 10(-5) M, 1.98 x 10(-4) M, and 2.1 x 10(-6) M, respectively. The secondary-alcohol dehydrogenase activity was inhibited by metal-chelating agents and by strong thio reagents such as p-hydroxymercuribenzoate and 5,5'-dithiobis(2-nitrobenzoic acid). The substrate specificity, and mobility on gel electrophoresis of secondary-alcohol dehydrogenase and primary-alcohol dehydrogenases are compared. Secondary-alcohol dehydrogenase oxidizes preferentially the (-)-2-butanol. This is different from primary-alcohol dehydrogenase from bakers' yeast which oxidizes only the (+)-2-butanol. This may be explained in terms of the structure of the enzymes.
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PMID:Stereospecificity and other properties of a novel secondary-alcohol-specific alcohol dehydrogenase. 703 Jul 36

The relationships among anserine (beta-alanyl-1-methyl-L-histidine), carnosine (beta-alanyl-L-histidine), free histidine, and histamine metabolism were examined in rats wounded by dorsal skin incision. Following wounding, rats were treated with either a histamine liberator (compound 48/80) or a histidine decarboxylase inhibitor (4-imidazolyl-3-amino-2-butanone). The liberator greatly enhanced wounded skin-breaking strength and collagen deposition at the wound site, while the histidine decarboxylase inhibitor reduced skin-breaking strength and collagen deposition. In the second experiment of this study, histamine or histidine treatment was shown to prevent trauma-induced reductions of tissue carnosine but was less effective in ameliorating tissue anserine loss. The results illustrate an interaction between imidazole dipeptides and stress and suggest that carnosine acts as a histidine reserve in relation to histamine synthesis during trauma.
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PMID:Histamine synthesis, imidazole dipeptides, and wound healing. 706 98

Structurally related cationic and uncharged compounds have been studied as inhibitors of hydrolysis by acetylcholinesterase of acetylcholine and its uncharged carbon analog, 3,3-dimethylbutyl acetate. Similar effects of the inhibitors on hydrolysis of the two substrates indicate that the quaternary ammonium group of acetylcholine and the neopentyl group of 3,3-dimethylbutyl acetate bind at the same subsite. Comparison of (CH3)3+NCH2CH2CH2COCH3 (Compound I), Ki = 0.02 mM, and its tertiary homologue, (CH3)2-+NHCH2CH2CH2COCH3 (Compound V), Ki = 0.75 mM, with a secondary isomer of Compound I, 3-oxo-(N-tert-butyl)-butanaminium, (CH3)3C+NH2CH2CH2COCH3 (Compound II), Ki = 0.15 mM, and its lower homologue, (CH3)2CH+NH2CH2CH2COCH3 (Compound IX), Ki = 2 mM, attests to the importance of the branched trimethyl structure and the smaller effect of hydrophobicity of the quaternary ammonium structure. This is supported by competitive inhibition by tert-butyl ammonium, (CH3)3C+NH3 (Compound IV), Ki = 0.45 mM, compared with mixed inhibition by its quarternary isomer, (CH3)4+N (Compound VII), Ki = 1.5 mM, and choline (Compound VI), Ki = 1.0 mM. Uncharged analogues of Compound II, 4-tert-butylthio-2-butanone, (CH3)3CSCH2CH2COCH3 (Compound III), Ki = 0.4 mM, and 4-tert-butoxy-2-butanone, (CH3)3COCH2CH2COCH3 (Compound VIII), Ki = 1.6 mM, and of Compound VI, 3,3-dimethylbutanol (Compound XI), Ki = 7.5 mM, indicate that positive charge contributes factors of 3 to 10 to binding. This may be attributed to peripheral negative charges, present at pH 7-8 in the enzyme of isoelectric point approximately 5, indicating that the binding subsite may be explored more specifically by tert-butyl than by charged reagents.
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PMID:Cationic and uncharged substrates and reversible inhibitors in hydrolysis by acetylcholinesterase (EC 3.1.1.7). The trimethyl subsite. 726 27

A pharmacokinetic model is presented to describe the biotransformation of 2-butanol (2-OL) and its metabolites (2-butanone, 3-hydroxy-2-butanone, and 2, 3-butanediol) using in vivo experimental blood concentration. A flow limited model is developed to simulate 2-OL, 2-butanone (2-ONE), 3-hydroxy-2-butanone (3H-2B), and 2,3-butanediol (2,3-RD) blood concentrations in rats after oral administration of 2-OL. Assuming the only important site of 2-OL biotransformation is the liver, the tissues included are the liver and a volume of distribution, essentially body water in the case of 2-OL and its metabolites. A distribution coefficient is found to be necessary to describe the low concentration of 3H-2B in blood after administration of 2-OL. The need for this coefficient may be due to partitioning, binding, or altered transport rates from the liver. Inhibition of 2-ONE metabolism to 3H-2B by 2-OL has been included to explain a time delay in the appearance of 3H-2B after administration of 2-OL. Subsequent experimental verification confirms the mixed function oxidase inhibitory properties of 2-OL. The model is able to simulate blood concentrations and elimination of all four compounds after the oral administration of 2-OL. Additionally, the model also simulates the results obtained after i.v. administration of 3H-3B and 2,3-BD.
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PMID:Pharmacokinetics of 2-butanol and its metabolites in the rat. 733 59

A variety of chemicals potentiate haloalkane-induced liver injury, but structure-activity relationships are not apparent. Recent studies have shown that one structural determinant, a carbonyl moiety, is common to several potentiating agents. Thus five ketonic chemicals (acetone, 2-butanone, methyl n-butylketone, 2,5-hexanedione, Kepone) and three chemicals that are metabolized to ketones (isopropranol, 2-butanol, n-hexane) potentiate the liver injury produced by one or more haloalkanes. Potentiation also has been observed when haloalkanes are administered to animals in a state of metabolic ketosis produced by alloxan-induced diabetes or by 1,3-butanediol administration. These observations are consistent with the hypothesis that administration or generation of ketonic substances increases the susceptibility of the liver to the toxic actions of haloalkanes.
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PMID:Modification of haloalkane-induced hepatotoxicity by exogenous ketones and metabolic ketosis. 742 55

A sequential thin-layer chromatographic method (STLC) has been developed to analyze the two organophosphorus insecticides phosfolan (O,O-diethyl 1,3-dithiolan-2-ylidenephosphoramidate) and mephospholan (O,O-diethyl 4-methyl-1,3-dithiolan-2-ylidenephosphoramidate) and some of their possible degradation products. Gelman type SA, Instant Thin Layer Chromatography (ITLC) silicic acid-impregnated glass fiber sheets were first developed up to 6 cm with the primary solvent 2-butanone-1-butanol-water (9:3:1), then after drying, to 16 cm with the secondary solvent acetonitrile-n-hexane-benzene-acetic acid (80:40:40:1). This two-solvent sequential system separated each insecticide from its corresponding metabolites. The R1 values were: phosfolan, 0.69; ethylene dithioimido-carbonate hydrochloride, 0.08; ethylene dithiocarbonate, 0.90; potassium thiocyanate, 0.40; mephosfolan, 0.76; O,O-diethyl 4-hydroxymethyl-1,3-dithiolan-2-amidate, 0.83; propylene dithioimidocarbonate hydrochloride; 0.15 and propylene dithiocarbonate, 0.87.
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PMID:Sequential thin-layer chromatography of phosfolan, mephosfolan and related compounds. 746 76

The lumazine synthase/riboflavin synthase of Bacillus subtilis is a bifunctional enzyme complex catalysing the formation of riboflavin from 5-amino-6-(D-ribitylamino)-2,4(1H,3H)-pyrimidinedione and L-3,4-dihydroxy-2-butanone-4-phosphate via 6,7-dimethyl-8-ribityllumazine. The complex is composed of 3 alpha (riboflavin synthase) subunits and 60 beta (lumazine synthase) subunits and has a relative mass of 1 MDa. The 60 beta subunits are arranged in an icosahedral capsid enclosing the alpha trimer in the central core. The protein was crystallised, and an X-ray structure of the icosahedral capsid was obtained at 3.3 A resolution with a crystallographic R-factor of 0.33. Hollow, icosahedral capsids consisting of 60 beta subunits can be obtained by inhibitor-driven renaturation of isolated beta subunits. They catalyse the formation of 6,7-dimethyl-8-ribityllumazine at the same rate as the native alpha 3 beta 60 complex and can be crystallised in two different hexagonal and one monoclinic form. Crystallographic intensity data of the monoclinic crystals to a resolution of 2.4 A were obtained using synchrotron radiation and an image plate detector system. The orientation of the icosahedral molecules in the monoclinic cell was deduced by real space vector search procedures from a 3.5 A Patterson map. Phases were calculated from the model of the alpha 3 beta 60 protein and were extended by cyclic averaging exploring the 30-fold redundancy of the electron density. The 2.4 A map allowed us to refine the existing atomic model of lumazine synthase. The refined model includes 154 amino acid residues, one inhibitor molecule, 58 water molecules and one phosphate ion. Applying non-crystallographic-symmetry restraints the crystallographic R-factor is 16.7% for 100,092 reflections between 10 and 2.4 A. The chain folding of the beta subunits is closely similar to the native alpha 3 beta 60 enzyme. The lumazine synthase bears resemblance to the sugar binding proteins. The significantly higher resolution compared to the alpha 3 beta 60 structure determination allows a detailed description of the substrate analogue binding site. The environment of the 5-nitro-6-(D-ribitylamino)-2,4(1H,3H)-pyrimidinedione inhibitor is particularly rigid, and the chain segments involved in forming the active site are highly conserved for lumazine synthases of different species. A residual density feature in the final map is interpreted as a bound phosphate which mimics the binding of the second substrate. We discuss the reaction mechanism on this structural basis.
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PMID:Studies on the lumazine synthase/riboflavin synthase complex of Bacillus subtilis: crystal structure analysis of reconstituted, icosahedral beta-subunit capsids with bound substrate analogue inhibitor at 2.4 A resolution. 747 9

Ozonizing of exhausted motor transport gases increases their toxicity. The most dangerous of formed substances are: nonanal, acetophenon, octanal, benzaldehyde, heptanal, decanal, 2-butanone.
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PMID:[Hygienic evaluation of photochemical transformation of automobile exhaust fumes as effected by ozone]. 751 9

The Microtox EC50 values for the following ketones are reported in the following homologous series: straight chain methyl ketones (acetone, 2-butanone, 2-pentanone, 2-hepatonone, 2-octanone, 2-decanone, and 2-tridecanone); methyl ketones substituted at one alpha carbon (3-methyl-2-butanone; 3,3-dimethyl-2-butanone); methyl substituted at two alpha carbons (2,4-dimethyl-3-pentanone; 2,2,4,4-tetramethyl-3-pentanone); phenyl groups replacing methyl in acetone (acetophenone; benzophenone); methyl groups substituted at the alpha carbons of cyclohexanone; and 2,3- 2,4-, and 2,5-hexanediones, most for the first time. While there were linear relationships between log EC50 and MW for the straight chain methyl ketones, and for methyl substitution at the alpha carbon for methyl ketones, there were no other linear relationships. As molecular weight increased, the EC50 values of soluble ketones decreased; as distance between two carbonyl groups decreased so too did EC50 values. Thus, for the ketones the geometry around the carbonyl group is an important determinant of toxicity as well as MW, water solubility, and octanol/water coefficient.
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PMID:Ketone EC50 values in the Microtox test. 753 64

6,7-Dimethyl-8-ribityllumazine, the immediate biosynthetic precursor of riboflavin, is synthesized by condensation of 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione with 3,4-dihydroxy-2-butanone 4-phosphate. The gene coding for 6,7-dimethyl-8-ribityllumazine synthase in Saccharomyces cerevisiae (RIB4) has been cloned by functional complementation of a mutant accumulating 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione, which can grow on riboflavin- or diacetyl- but not on 3,4-dihydroxy-2-butanone-supplemented media. Gene disruption of the chromosomal copy of RIB4 led to riboflavin auxotrophy and loss of enzyme activity. Nucleotide sequencing revealed a 169-base pair open reading frame encoding a 18.6-kDa protein. Hybridization analysis indicated that RIB4 is a single copy gene located on the left arm of chromosome XV. Overexpression of the RIB4 coding sequence in yeast cells under the control of the strong TEF1 promoter allowed ready purification of 6,7-dimethyl-8-ribityllumazine synthase to apparent homogeneity by a simple procedure. Initial structural characterization of 6,7-dimethyl-8-ribityllumazine synthase by gel filtration chromatography and both nondenaturing pore limit and SDS-polyacrylamide gel electrophoresis showed that the enzyme forms a pentamer of identical 16.8-kDa subunits. The derived amino acid sequence of RIB4 shows extensive homology to the sequences of the beta subunits of riboflavin synthase from Bacillus subtilis and other prokaryotes.
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PMID:The Saccharomyces cerevisiae RIB4 gene codes for 6,7-dimethyl-8-ribityllumazine synthase involved in riboflavin biosynthesis. Molecular characterization of the gene and purification of the encoded protein. 755 56


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