Graphical rules for enzyme-catalysed rate laws.
Ontology highlight
ABSTRACT:
SUBMITTER: Chou KC
PROVIDER: S-EPMC1162468 | biostudies-other | 1980 Jun
REPOSITORIES: biostudies-other
Similar Datasets
Project description:BackgroundMore states and localities are passing restrictions on smoking in public places and workplaces.PurposeTo determine what, if any, association exists between enactment of strong laws making public places or workplaces smokefree on adoption of voluntary smokefree-home policies, particularly whether such laws are associated with increased smoking at home.MethodsLogistic regressions were used to estimate the OR of a person living with a 100% smokefree-home rule as a function of individual characteristics, household composition, and whether or not the residential region is covered by clean indoor air laws. The data came from successive waves of the Tobacco Use Supplement to Current Population Survey (TUS-CPS) for the years 1992-2007, and the American Nonsmokers' Rights Foundation database of state and local government clean indoor air laws. Analysis was conducted in 2010 and 2011.ResultsLiving in a county fully covered by a 100% clean indoor air law in workplaces or restaurants or bars is associated with an increased likelihood of having a voluntary 100% smokefree-home rule both for people living with smokers (OR=7.76, 95% CI=5.27, 11.43) and not living with smokers (OR=4.12, 95% CI=3.28, 5.16).ConclusionsStrong clean indoor air laws are associated with large increases in voluntary smokefree-home policies both in the homes with and without smokers. These results support the hypothesis of norm spreading of clean indoor air laws.
| S-EPMC3222862 | biostudies-literature
Project description:Generalized rate equations covering all mechanisms giving hyperbolic initial-rate kinetics with stoichiometry A in equilibrium P, A in equilibrium P + Q, A + B in equilibrium P and A + B in equilibrium P + Q were integrated. The results are regular and reasonably economical.
| S-EPMC1144258 | biostudies-other
Project description:Integrated rate equations are presented that describe irreversible enzyme-catalysed first-order and second-order reactions. The equations are independent of the detailed mechanism of the reaction, requiring only that it be hyperbolic and unbranched. The results should be directly applicable in the laboratory.
| S-EPMC1144673 | biostudies-other
Project description:The growing applications of carbon nanotubes (CNTs) inevitably increase the risk of exposure to this potentially toxic nanomaterial. In an attempt to address this issue, research has been implemented to study the biodegradation of CNTs. In particular, myeloperoxidase (MPO), an enzyme expressed by inflammatory cells of animals including humans, catalyse the degradation of oxidized carbon nanomaterials. While reactive intermediates generated by MPO efficiently degrade oxidized single-walled carbon nanotubes (o-SWCNTs); the exact mechanism of enzyme-catalysed biodegradation remains ambiguous. In this work, we tried to explain enzymatic oxidation in terms of redox potentials by employing competitive substrates for MPO such as chloride, which is oxidized by MPO to form a strong oxidant (hypochlorite), and antioxidants that have lower redox potentials than CNTs. Employing transmission electron microscopy, Raman spectroscopy, and vis-NIR absorption spectroscopy, we demonstrate that the addition of antioxidants, L-ascorbic acid and L-glutathione, with or without chloride significantly mitigates MPO-catalysed biodegradation of o-SWCNTs. This study focuses on a fundamental understanding of the mechanisms of enzymatic biodegradation of CNTs and the impact of antioxidants on these pathways.
| S-EPMC3634595 | biostudies-literature
Project description:Heat capacity changes are emerging as essential for explaining the temperature dependence of enzyme-catalysed reaction rates. This has important implications for enzyme kinetics, thermoadaptation and evolution, but the physical basis of these heat capacity changes is unknown. Here we show by a combination of experiment and simulation, for two quite distinct enzymes (dimeric ketosteroid isomerase and monomeric alpha-glucosidase), that the activation heat capacity change for the catalysed reaction can be predicted through atomistic molecular dynamics simulations. The simulations reveal subtle and surprising underlying dynamical changes: tightening of loops around the active site is observed, along with changes in energetic fluctuations across the whole enzyme including important contributions from oligomeric neighbours and domains distal to the active site. This has general implications for understanding enzyme catalysis and demonstrating a direct connection between functionally important microscopic dynamics and macroscopically measurable quantities.
| S-EPMC5862990 | biostudies-literature
Project description:Pericyclic reactions-which proceed in a concerted fashion through a cyclic transition state-are among the most powerful synthetic transformations used to make multiple regioselective and stereoselective carbon-carbon bonds. They have been widely applied to the synthesis of biologically active complex natural products containing contiguous stereogenic carbon centres. Despite the prominence of pericyclic reactions in total synthesis, only three naturally existing enzymatic examples (the intramolecular Diels-Alder reaction, and the Cope and the Claisen rearrangements) have been characterized. Here we report a versatile S-adenosyl-l-methionine (SAM)-dependent enzyme, LepI, that can catalyse stereoselective dehydration followed by three pericyclic transformations: intramolecular Diels-Alder and hetero-Diels-Alder reactions via a single ambimodal transition state, and a retro-Claisen rearrangement. Together, these transformations lead to the formation of the dihydropyran core of the fungal natural product, leporin. Combined in vitro enzymatic characterization and computational studies provide insight into how LepI regulates these bifurcating biosynthetic reaction pathways by using SAM as the cofactor. These pathways converge to the desired biosynthetic end product via the (SAM-dependent) retro-Claisen rearrangement catalysed by LepI. We expect that more pericyclic biosynthetic enzymatic transformations remain to be discovered in naturally occurring enzyme 'toolboxes'. The new role of the versatile cofactor SAM is likely to be found in other examples of enzyme catalysis.
| S-EPMC5679075 | biostudies-literature
Project description:To delineate further the pathway of pepsin-catalysed reactions, three types of experiments were performed: (a) the enzyme-catalysed hydrolysis of a number of di- and tri-peptide substrates was studied with a view to observing the rate-determining breakdown of a common intermediate; (b) the interaction of pepsin with several possible substrates for which ;burst' kinetics might be expected was investigated; (c) attempts were made to trap a possible acyl-enzyme intermediate with [(14)C]methanol in both a hydrolytic reaction (with N-acetyl-l-phenylalanyl-l-phenylalanylglycine) and in a ;virtual' reaction (with N-acetyl-l-phenylalanine) under conditions where extensive hydrolysis or (18)O exchange is known to occur. It is concluded that (i) intermediates in pepsin-catalysed reactions (aside from the Michaelis complex) occur subsequently to the rate-determining transition state, and (ii) an acyl-enzyme intermediate, if such is formed, cannot be trapped with [(14)C]methanol in these systems.
| S-EPMC1184644 | biostudies-other
Project description:Pericyclic reactions are powerful transformations for the construction of carbon-carbon and carbon-heteroatom bonds in organic synthesis. Their role in biosynthesis is increasingly apparent, and mechanisms by which pericyclases can catalyse reactions are of major interest1. [4+2] cycloadditions (Diels-Alder reactions) have been widely used in organic synthesis2 for the formation of six-membered rings and are now well-established in biosynthesis3-6. [6+4] and other 'higher-order' cycloadditions were predicted7 in 1965, and are now increasingly common in the laboratory despite challenges arising from the generation of a highly strained ten-membered ring system8,9. However, although enzyme-catalysed [6+4] cycloadditions have been proposed10-12, they have not been proven to occur. Here we demonstrate a group of enzymes that catalyse a pericyclic [6+4] cycloaddition, which is a crucial step in the biosynthesis of streptoseomycin-type natural products. This type of pericyclase catalyses [6+4] and [4+2] cycloadditions through a single ambimodal transition state, which is consistent with previous proposals11,12. The [6+4] product is transformed to a less stable [4+2] adduct via a facile Cope rearrangement, and the [4+2] adduct is converted into the natural product enzymatically. Crystal structures of three pericyclases, computational simulations of potential energies and molecular dynamics, and site-directed mutagenesis establish the mechanism of this transformation. This work shows how enzymes are able to catalyse concerted pericyclic reactions involving ambimodal transition states.
| S-EPMC6944468 | biostudies-literature
Project description:(S)-2-hydroxypropylphosphonate ((S)-2-HPP) epoxidase (HppE) is a mononuclear non-haem-iron-dependent enzyme responsible for the final step in the biosynthesis of the clinically useful antibiotic fosfomycin. Enzymes of this class typically catalyse oxygenation reactions that proceed via the formation of substrate radical intermediates. By contrast, HppE catalyses an unusual dehydrogenation reaction while converting the secondary alcohol of (S)-2-HPP to the epoxide ring of fosfomycin. Here we show that HppE also catalyses a biologically unprecedented 1,2-phosphono migration with the alternative substrate (R)-1-HPP. This transformation probably involves an intermediary carbocation, based on observations with additional substrate analogues, such as (1R)-1-hydroxyl-2-aminopropylphosphonate, and model reactions for both radical- and carbocation-mediated migration. The ability of HppE to catalyse distinct reactions depending on the regio- and stereochemical properties of the substrate is given a structural basis using X-ray crystallography. These results provide compelling evidence for the formation of a substrate-derived cation intermediate in the catalytic cycle of a mononuclear non-haem-iron-dependent enzyme. The underlying chemistry of this unusual phosphono migration may represent a new paradigm for the in vivo construction of phosphonate-containing natural products that can be exploited for the preparation of new phosphonate derivatives.
| S-EPMC3725809 | biostudies-literature
Project description:In this article, we conduct a comprehensive analysis of the effect of parental involvement (PI) laws on the incidence of abortions to minors in the United States. We contribute to the extant literature in several ways. First, we explore differences in estimates of the effect of PI laws across time that may result from changes in contraception, the composition of pregnant minors, abortion access in nearby states, and differences in how these laws are enforced. We find that PI laws enacted before the mid-1990s are associated with a 15% to 20% reduction in abortions to minors, but PI laws enacted after this time are not associated with declines in abortions to minors. Second, we assess the role of out-of-state travel by minors and find that it is not a significant factor moderating the effect of PI laws. Third, we use a synthetic control approach to explore state-level heterogeneity in the effect of PI laws and find large differences in the effect of PI laws on abortions to minors by state that appear unrelated to the type of PI law or whether contiguous states have enacted PI laws. Finally, we show that estimates of the effect of PI laws using data from either the Centers for Disease Control or the Guttmacher Institute do not differ qualitatively once differences in the states and years available across these data are harmonized.
| S-EPMC7121997 | biostudies-literature