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)

Peptide fluoromethyl ketones have been synthesized for the first time. The inhibitor 3-(N-benzyloxycarbonylphenylalanylamido)-DL-1-fluoro-2-butanone (Z-Phe-AlaCH2F) was found to be a 30-fold more potent inactivator of human cathepsin B than 3-(N-benzyloxycarbonylphenylalanylamido)-L-1-diazo-2-butanone (Z-Phe-AlaCHN2), but less reactive than 3-(N-benzyloxycarbonylphenylalanylamido)-L-1-chloro-2-butanone (Z-Phe-AlaCH2Cl). The fluoromethyl ketone's increased potency over the diazomethyl ketone is mainly due to its tighter binding to cathepsin B, with little difference between their respective k3 values. Both Z-Phe-AlaCHN2 and Z-Phe-AlaCH2F were quite stable to high concentrations of dithiothreitol, while Z-Phe-AlaCH2Cl was rapidly destroyed by the thiol.
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PMID:Synthesis of peptide fluoromethyl ketones and the inhibition of human cathepsin B. 407 1

An inducible acetylesterase (EC 3.1.1.6) that hydrolyzes ethyl acetate, an intermediate in the degradation of 2-butanone by Nocardia strain LSU-169, was purified. The polypeptide molecular weight as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was 39,500, and the enzyme molecular weight determined by sucrose density gradient centrifugation was 84,000. The purified enzyme demonstrated aggregation in polyacrylamide gels. The esterase hydrolyzed p-nitrophenyl acetate, ethyl acetate, and methyl acetate; however, enzymatic hydrolysis of phosphates, sulfates, dipeptides, lactones, or the ethyl esters of N-benzoyl-l-tyrosine could not be detected. The apparent K(m) for esterase activity with p-nitrophenyl acetate as the substrate was 6.7 x 10(-5) M, and the maximal velocity (V) was 1,223 mumol/min per mg of protein at 30 C. With ethyl acetate as the substrate, the apparent K(m) was 3.6 x 10(-4) M and V was 1,026 mumol/min per mg of protein. No significant inhibition of esterase activity was obtained with organophosphates, mercuric compounds, eserine sulfate, sodium arsanilate, NaF, CaCl(2), CoCl(2), or MnCl(2). At concentrations from 7 x 10(-4) to 4 x 10(-3) M, 2-butanol and primary alcohols with chain lengths of four or more carbons inhibited esterase activity from 59 to 86%. Linear noncompetitive inhibition of esterase activity by 3-methyl-1-butanol with a K(i) of 1.0 x 10(-3) M was demonstrated.
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PMID:Purification and characterization of the nocardial acetylesterase involved in 2-butanone degradation. 443 55

n-Butane was metabolized in Mycobacterium vaccae (JOB5) via terminal oxidation. This organism metabolized 2-butanone through propionate (or propionyl coenzyme A). Subterminal oxidation in M. vaccae was apparently limited to propane.
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PMID:Metabolism of n-butane and 2-butanone by Mycobacterium vaccae. 445 91

The reported occurrence of synergistic false-positive coliform reactions on M-Endo MF medium was investigated. The objectives of the study were (i) to isolate populations of bacteria which produced such false-positive reactions, (ii) to determine whether false-positive sheen reactions are a result of synergistic interaction, and (iii) to determine the metabolic intermediates involved in false-positive sheen production. Samples of river water were subjected to coliform analysis by the membrane filter technique with M-Endo MF medium. Suspect sheen-forming colonies were analyzed to determine purity and identity of cultures. Mixed cultures were separated, and individual isolates were examined for sheen production. The isolates not producing a sheen were recombined and tested further for sheen production. Those mixtures reproducing the sheen were characterized biochemically and tested to determine the metabolic intermediates involved. Chromatographic analysis of the metabolites showed that individual isolates produced an assortment of neutral organic compounds including 2-butanone, 2,3-butanedione, formaldehyde, and butyraldehyde, whereas acetaldehyde or propionaldehyde was produced only by the mixed cultures. Tests showed that both propionaldehyde and acetaldehyde could react to produce a sheen on M-Endo medium. The conclusion was reached that synergistic false-positive coliform reactions do indeed occur on M-Endo MF medium.
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PMID:Synergistic false-positive coliform reaction on M-Endo MF medium. 492 83

N-Bromoacetylethanolamine phosphate and 3-bromo-1,4-dihydroxy-2-butanone 1,4-bisphosphate have been tested in order to study the hexose phosphate binding sites of a bifunctional enzyme, fructose-6-P,2-kinase:fructose-2,6-bisphosphatase. N-Bromoacetylethanolamine phosphate is a competitive inhibitor with respect to fructose-6-P (Ki = 0.24 mM) and a noncompetitive inhibitor with ATP (Ki = 0.8 mM). The reagent inactivates fructose-6-P,2-kinase but not fructose-2,6-bisphosphatase, and the inactivation is prevented by fructose-6-P. The inactivation reaction follows pseudo first-order kinetics to completion and with increasing concentrations of N-bromoacetylethanolamine phosphate a rate saturation effect is observed. The concentration of the reagent giving the half-maximum inactivation is 2.2 mM and the apparent first order rate constant is 0.0046 s-1. The enzyme alkylated by N-bromoacetylethanolamine-P has lost over 90% of the kinase activity, retains nearly full activity of fructose-2,6-bisphosphatase, and its inhibition by fructose-6-P is not altered. 3-Bromo-1,4-dihydroxy-2-butanone 1,4-bisphosphate is also a competitive inhibitor of fructose-6-P,2-kinase with respect to fructose-6-P in the forward reaction and fructose-2,6-P2 in the reverse direction. This reagent inhibits 93% of fructose-6-P,2-kinase but activates fructose-2,6-bisphosphatase 3.7-fold. 3-Bromo-1,4-dihydroxy-2-butanone 1,4-bisphosphate alters the fructose-2,6-P2 saturation kinetic curve from negative cooperativity to normal Michaelis-Menten kinetics with K0.5 of 0.8 microM. The reagent, however, has no effect on the fructose-6-P inhibition of the phosphatase. These results strongly suggest that hexose phosphate binding sites of fructose-6-P,2-kinase and fructose-2,6-bisphosphatase are distinct and located in different regions of this bifunctional enzyme.
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PMID:Hexose phosphate binding sites of fructose-6-phosphate,2-kinase:fructose-2,6-bisphosphatase. Interaction with N-bromoacetylethanolamine phosphate and 3-bromo-1,4-dihydroxy-2-butanone 1,4-bisphosphate. 609 36

Microsomes have the potential to oxidize alcohols by two pathways, one dependent on hydroxyl radicals (.OH) and the other dependent on cytochrome P-450 in which .OH does not seem to be involved. The possibility that these two pathways may display differences in stereospecificity was evaluated by comparing the oxidation of (+)-2-butanol, (-)-2-butanol, and racemic 2-butanol. Microsomes oxidized 2-butanol to 2-butanone by a reaction which was partially sensitive to carbon monoxide and to competitive .OH scavengers. Desferrioxamine, which completely blocks the production of .OH by microsomes, inhibited the oxidation of ethanol by about 60%, while the oxidation of 2-butanol and 1-butanol was decreased by only 30%. Vmax values for the oxidation of ethanol, 1-butanol, and 2-butanol were 17.7, 6.2, and 23.8 nmol min-1 (mg of protein)-1, respectively, in the absence of desferrioxamine and 5.9, 4.7, and 13.6 nmol min-1 (mg of protein)-1, respectively, in the presence of desferrioxamine. 2-Butanol appears to be a particularly good alcohol substrate for the cytochrome P-450 dependent pathway of alcohol oxidation. Chronic ethanol consumption, which induces the microsomal alcohol oxidizing system, resulted in a 3-fold increase in the rate of 2-butanol oxidation. Most of this increment reflected an increased rate of metabolism by the cytochrome P-450 pathway. A type 2 binding spectrum was observed for the interaction of 2-butanol with microsomes from ethanol-fed rats, but not with controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stereochemical studies on the cytochrome P-450 and hydroxyl radical dependent pathways of 2-butanol oxidation by microsomes from chow-fed, phenobarbital-treated, and ethanol-treated rats. 609 1

The extraction of lipids from rat liver mitochondrial membranes by 2-butanone treatment inhibited the activity of membrane-bound monoamine oxidase -A but not -B. For the -B form, the apparent Michaelis constants of the enzyme towards oxygen and the maximum molecular turnover numbers obtained when beta-phenethylamine and benzylamine were used as substrates were not significantly changed by the lipid-depletion procedure, but the values of the Michaelis constant towards benzylamine was significantly increased after lipid-depletion. The differential sensitivity of beta-phenethylamine and benzylamine oxidation to inhibition by Tris-HCl was not changed after lipid-depletion. The results are consistent with the hypothesis that the mitochondrial membrane lipids, while essential for the activity of the -A form of the enzyme in rat liver, play a more subtle modulatory role in the activity of the -B form.
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PMID:The effect of lipid-depletion on the kinetic properties of rat liver monoamine oxidase-B. 610 40

The NAD-dependent oxidation of ethanol, 2,3-butanediol, and other primary and secondary alcohols, catalyzed by alcohol dehydrogenases derived from Penicillium charlesii, was investigated. Alcohol dehydrogenase, ADH-I, was purified to homogeneity in a yield of 54%. The enzyme utilizes several primary alcohols as substrates, with Km values of the order of 10(-4) M. A Km value of 60 mM was obtained for R,R,-2,3-butanediol. The stereospecificity of the oxidation of 2-butanol was investigated, and S-(+)-2-butanol was found to be oxidized 2.4 times faster than was R-(-)-2-butanol. The reduction of 2-butanone was shown to produce S-(+)-2-butanol and R-(-)-butanol in a ratio of 7:3. ADH-I is the primary isozyme of alcohol dehydrogenase present in cultures utilizing glucose as the sole carbon source. The level of alcohol dehydrogenase activity increased 7.6-fold in mycelia from cultures grown with glucose and 2,3-butanediol (0.5%) as carbon sources compared with the activity in cultures grown on only glucose. Two additional forms of alcohol dehydrogenase, ADH-II and ADH-III, were present in the cultures supplemented with 2,3-butanediol. These forms of alcohol dehydrogenase catalyze the oxidation of ethanol and 2,3-butanediol. These data suggest that P. charlesii carries out an oxidation of 2,3-butanediol which may constitute the first reaction in the degradation of 2,3-butanediol as well as the last reaction in the mixed-acid fermentation. Alcohol dehydrogenase activities in P. charlesii may be encoded by multiple genes, one which is expressed constitutively and others whose expression is inducible by 2,3-butanediol.
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PMID:Occurrence of multiple forms of alcohol dehydrogenase in Penicillium supplemented with 2,3-butanediol. 638 55

Recent studies have indicated that (1) ketonic solvents and ketogenic chemicals can potentiate the nephrotoxic and hepatotoxic effects of one or more halogenated hydrocarbons; and (2) the relative ability of ketones to potentiate the liver injury produced by chloroform (CHCl3) may be influenced by the carbon skeleton length of the ketone. Although five ketones (acetone, 2-butanone, 2-pentanone, 2-hexanone, (HX), and 2-heptanone) increased CHCl3-induced kidney and liver injury in male, Fischer 344 rats, no relationship between ketone chain length and potentiating capacity was observed. HX potentiated the CHCL3-induced depletion of hepatic glutathione content and increased the irreversible binding of 14CHCl3-derived radiolabel to hepatic constituents. In contrast, CHCl3 did not alter glutathione content in the renal cortex of either vehicle- or HX-pretreated rats. Although HX increased the binding of 14C from 14CHCl3 to renal cortical macromolecules, the magnitude of the increase was unremarkable, approaching only the extent of hepatic 14C binding in vehicle-pretreated rats challenged with 14CHCl3. Since the severity of renal and hepatic injury was comparable in rats receiving the combination of HX + CHCl3, it appeared that HX potentiated CHCl3 nephro- and hepatotoxicity by different mechanisms. Ketone pretreatment did not potentiate the renal injury produced by potassium dichromate or hexachloro-1,3-butadiene.
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PMID:Nephrotoxic interactions between ketonic solvents and halogenated aliphatic chemicals. 639 13

Chloroform (CHCl3)-induced hepato- and nephrotoxicity was evaluated in male, Fischer 344 rats pretreated with various dosages (1.0 to 15.0 mmol/kg, po) of acetone (Ac), 2-butanone (Bu), 2-pentanone (Pn), 2-hexanone (Hx), or 2-heptanone (Hp). The CHCl3 challenge dosage (0.5 ml/kg, ip) produced slight centrilobular hydropic degeneration and patchy degeneration and necrosis in the proximal tubules of corn oil-pretreated rats. Each of the ketones studied produced a dose-related potentiation of CHCl3 liver and kidney injury. CHCl3 produced extensive tubular and centrilobular necrosis when administered to ketone-pretreated rats. The relationship between ketone dosage and the magnitude of the potentiated response was nonlinear. Maximum potentiation of CHCl3 toxicity occurred in the dosage range of 5.0 to 10.0 mmol ketone/kg. Ketone dosages greater than 10.0 mmol/kg were associated with a reduction in the degree of CHCl3 injury. At the lowest ketone dosage (1.0 mmol/kg), potentiating capacity appeared to be related to ketone carbon skeleton length. No differences in potentiating capacity were discernable between the ketones at dosages of 5.0 to 10.0 mmol/kg. Thus, whether or not there is a relationship with carbon chain length and potentiation depends upon the dosage of the ketone.
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PMID:Dose-response relationships in ketone-induced potentiation of chloroform hepato- and nephrotoxicity. 650 71


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