Return to Work and Participation in Society After Out-of-Hospital Cardiac Arrest.

Background: The aim of this study was to describe out-of-hospital cardiac arrest (OHCA) survivors' ability to participate in activities of everyday life and society, including return to work. The specific aim was to evaluate potential effects of cognitive impairment.

Methods And Results: Two hundred eighty-seven OHCA survivors included in the TTM trial (Target Temperature Management) and 119 matched control patients with ST-segment-elevation myocardial infarction participated in a follow-up 180 days post-event that included assessments of participation, return to work, emotional problems, and cognitive impairment.

The mechanism of Compound I formation revisited.

The most recently proposed mechanisms for the formation of the Compound I intermediates of the peroxidases and catalases have been based on the crystallographic elucidation of the enzyme structures. It has been assumed that these mechanisms are compatible with an earlier proposal of the formation of a reversible enzyme-substrate intermediate called Compound 0, which was based on data that pre-dated the availability of the enzyme structures. However, it is argued here that this is not the case and some modifications of the existing mechanism are proposed which reconcile the structural, kinetic and energetic data for the reactions.

How do enzymes work? Effect of electron circuits on transition state acid dissociation constants.

The effect of electron flow through a complete circuit on transition state acid dissociation constants is used to explain the remarkable catalysis observed in a redox reaction, the formation of compound I from native peroxidase. The explanation for the huge shift in the dissociation constant of a distal histidine residue, in going from the resting enzyme to the transition state, is a complete electron circuit through many amino acid residues and hydrogen bonds which prevents the development of localized charge. The key feature is electron flow through the circuit at the instant that proton transfer is occurring in the opposite direction.

Mechanism of reaction of myeloperoxidase with hydrogen peroxide and chloride ion.

The reaction of myeloperoxidase compound I (MPO-I) with chloride ion is widely assumed to produce the bacterial killing agent after phagocytosis. Two values of the rate constant for this important reaction have been published previously: 4.7 x 106 M-1.

Peroxidase-catalyzed halide ion oxidation.

The first complete mechanistic analysis of halide ion oxidation by a peroxidase was that of iodide oxidation by horseradish peroxidase. It was shown conclusively that a two-electron oxidation of iodide by compound I was occurring. This implied that oxygen atom transfer was occurring from compound I to iodide, forming hypoiodous acid, HOI.

The reaction rates of NO with horseradish peroxidase compounds I and II.

In this study the reactions between nitric oxide (NO) and horseradish peroxidase (HRP) compounds I and II were investigated. The reaction between compound I and NO has biphasic kinetics with a clearly dominant initial fast phase and an apparent second-order rate constant of (7.0 +/- 0.

Kinetics of oxidation of serotonin by myeloperoxidase compounds I and II.

The oxidation of serotonin (5-hydroxytryptamine) by the myeloperoxidase intermediates compounds I and II was investigated by using transient-state spectral and kinetic measurements at 25.0 +/- 0.1 degrees C.

Oxidation of clozapine and ascorbate by myeloperoxidase.

The kinetics and spectra of the reactions of clozapine with compounds I and II of myeloperoxidase were investigated using both single- and sequential-mixing stopped-flow techniques, steady-state kinetics, and spectrophotometric measurements. The results show conclusively that both compounds I and II are reduced in one-electron reactions with clozapine. At pH 7.

Reactions of prostaglandin endoperoxide synthase with hydroperoxide and reducing substrates under single turnover conditions.

The peroxidase reaction of prostaglandin endoperoxide synthase was investigated by transient state kinetics using stoichiometric amounts of substrates. The rate constants for the conversion of compound I to intermediate II determined with a stoichiometric amount of hydroperoxide were found to be lower by an order of magnitude than when an excess of hydroperoxide was used. The difference was attributed to ability of the compound I of prostaglandin endoperoxide synthase to be reduced by the excess of hydroperoxide.

Coupling of the peroxidase and cyclooxygenase reactions of prostaglandin H synthase.

Interrelations between peroxidase and cyclooxygenase reactions catalyzed by prostaglandin endoperoxide synthase (prostaglandin H synthase) were analyzed in terms of the mutual influence of these reactions. The original branched-chain mechanism predicts competition between these two reactions for enzyme, so that peroxidase cosubstrate should inhibit the cyclooxygenase reaction and the cyclooxygenase substrate is expected to inhibit the peroxidase reaction. In stark contrast, the peroxidase reducing substrate is well known to strongly stimulate the cyclooxygenase reaction.

The proofreading pathway of bacteriophage T4 DNA polymerase.

The base analog, 2-aminopurine (2AP), was used as a fluorescent reporter of the biochemical steps in the proofreading pathway catalyzed by bacteriophage T4 DNA polymerase. "Mutator" DNA polymerases that are defective in different steps in the exonucleolytic proofreading pathway were studied so that transient changes in fluorescence intensity could be equated with specific reaction steps. The G255S- and D131N-DNA polymerases can hydrolyze DNA, the final step in the proofreading pathway, but the mutator phenotype indicates a defect in one or more steps that prepare the primer-terminus for the cleavage reaction.

Reaction of prostaglandin endoperoxide synthase with cis,cis-eicosa-11,14-dienoic acid.

The pre-steady-state phase of the oxygenase reaction of prostaglandin endoperoxide synthase with cis,cis-eicosa-11, 14-dienoic acid has been studied using stopped flow techniques. Because some intermediate forms of prostaglandin endoperoxide synthase are spectrally indistinguishable, the enzyme and substrate transformations were monitored in parallel to simplify the interpretation of the kinetics. Over a wide range of conditions, the formation of the enzyme intermediate II, the form of compound I containing the tyrosyl radical, precedes substrate oxidation.

pH dependence and structural interpretation of the reactions of Coprinus cinereus peroxidase with hydrogen peroxide, ferulic acid, and 2,2'-azinobis.

Steady-state and transient-state analysis of Coprinus cinereus peroxidase, CIP (identical to Arthromyces ramosus peroxidase), was used to characterize the kinetics of the three fundamental steps in heme peroxidase catalysis: compound I (cpd I) formation, cpd I reduction, and compound II (cpd II) reduction. The rate constant k1 for cpd I formation determined by transient-state analysis is (9.9 +/- 0.

Mechanism of the oxidation of 3,5,3',5'-tetramethylbenzidine by myeloperoxidase determined by transient- and steady-state kinetics.

Earlier investigations of the oxidation of 3,5,3',5'-tetramethylbenzidine (TMB) using horseradish peroxidase and prostaglandin H-synthase have shown the formation of a cation free radical of TMB in equilibrium with a charge-transfer complex, consistent with either a two- or a one-electron initial oxidation. In this work, we exploited the distinct spectroscopic properties of myeloperoxidase and its oxidized intermediates, compounds I and II, to establish two successive one-electron oxidations of TMB. By employing stopped-flow techniques under transient-state and steady-state conditions, we also determined the rate constants for the elementary steps of the myeloperoxidase-catalyzed oxidation of TMB at pH 5.

Kinetic and spectral properties of pea cytosolic ascorbate peroxidase.

Sufficient highly purified native pea cytosolic ascorbate peroxidase was obtained to characterize some of its kinetic and spectral properties. Its rate constant for compound I formation from reaction with H2O2 is 4.O x 10(7) M-1 s-1, somewhat faster than is typical for peroxidases.

Effect of Trolox C on the oxygenation reaction of prostaglandin endoperoxide synthase with cis,cis-eicosa-11, 14-dienoic acid.

Trolox C, a water-soluble derivative of alpha-tocopherol, stimulates the oxygenation of cis,cis-eicosa-11, 14-dienoic acid (AH) by prostaglandin endoperoxide synthase at lower concentrations and suppresses the stimulated reaction at higher concentrations. Surprisingly, Trolox C does not affect the stoichiometric ratio between the rate of formation of the oxygenation product 11-hydroxy-12-trans, 14-cis-eicosadienoic acid (AOH) and the rate of disappearance of molecular oxygen. The ratio of the two rates, d[AOH]/-d[O2], remains constant at 2/1 for a series of Trolox C concentrations and in the absence of Trolox C.

Reactions of prostaglandin endoperoxide synthase and its compound I with hydroperoxides.

The reactions of native prostaglandin endoperoxide synthase with structurally different hydroperoxides have been investigated by using kinetic spectrophotometric scan and conventional and sequential mixing stopped-flow experiments. The second order rate constants for compound I formation are (5.9 +/- 0.

pH and temperature dependence of the rate of compound I formation from the reaction of prostaglandin endoperoxide synthase with hydrogen peroxide.

The formation of primary oxidized compound of prostaglandin endoperoxide synthase, compound I, was studied as a function of pH and temperature using hydrogen peroxide as a substrate. Analysis of the results indicates that compound I formation is influenced by an ionizable group with a pKa of 4.06 +/- 0.

Kinetics of oxidation of tyrosine and dityrosine by myeloperoxidase compounds I and II. Implications for lipoprotein peroxidation studies.

The oxidation of lipoproteins is considered to play a key role in atherogenesis, and tyrosyl radicals have been implicated in the oxidation reaction. Tyrosyl radicals are generated in a system containing myeloperoxidase, H2O2, and tyrosine, but details of this enzyme-catalyzed reaction have not been explored. We have performed transient spectral and kinetic measurements to study the oxidation of tyrosine by the myeloperoxidase intermediates, compounds I and II, using both sequential mixing and single-mixing stopped-flow techniques.

Oxygenation reactions of prostaglandins endoperoxide synthase and soybean lipoxygenase. Surprising stoichiometry in the formation of hydroperoxy and hydroxy derivatives of cis,cis-eicosa-11,14-dienoic acid.

The stoichiometry of the oxygenation reaction of cis,cis-eicosa-11,14-dienoic acid catalyzed by prostaglandin endoperoxide synthase and soybean lipoxygenase has been investigated by using steady-state initial rate measurements. The rate of product formation (conjugated diene hydroperoxy and hydroxy derivatives) was followed spectrophotometrically at 235 nm, and the rate of oxygen consumption was measured polarographically. The ratio of the two rates, d[conjugated diene/-d[O2], is 2/1 for the prostaglandin endoperoxide synthase catalyzed reaction and 1/1 for the lipoxygenase reaction.

Transient and steady-state kinetics of the oxidation of scopoletin by horseradish peroxidase compounds I, II and III in the presence of NADH.

Scopoletin, a naturally occurring fluorescent component of some plants and a proven plant growth inhibitor, is a known reactant with peroxidase. However, the kinetics of the elementary steps of the reaction have never been investigated, nor has the quantitative effect of interfering substances ever been explored in detail, despite the fact that scopoletin is widely used in a peroxidase assay for H2O2. In this work, we employed both transient-state and steady-state methods to determine the second-order rate constants for the oxidation of scopoletin by the horseradish peroxidase (HRP) intermediate compounds I and II: (3.

One-electron oxidations by peroxidases.

1. Peroxidases typically follow the reaction cycle: native enzyme-->compound I-->compound II-->native enzyme, in which the latter two steps involve hydrogen atom transfer from substrate to enzyme. 2.

Rate enhancement of compound I formation of barley peroxidase by ferulic acid, caffeic acid, and coniferyl alcohol.

Reactions of barley peroxidase 1 were studied using transient-state and steady-state kinetics at pH 3.96, 25 degrees C, and 0.1 M ionic strength, in both the presence and the absence of 1 mM calcium ion.