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Record W2324073402 · doi:10.3184/007967405779134029

Kinetics and Mechanisms of Mammalian Heme Peroxidase Reactions

2005· article· en· W2324073402 on OpenAlexaff
H. Brian Dunford

Bibliographic record

VenueProgress in Reaction Kinetics and Mechanism · 2005
Typearticle
Languageen
FieldMedicine
TopicInflammatory mediators and NSAID effects
Canadian institutionsUniversity of Alberta
Fundersnot available
KeywordsChemistryMyeloperoxidasePeroxidaseArachidonic acidHypochlorous acidCyclooxygenaseStereochemistryHemeBiochemistryMechanism of actionPeroxideEnzymeOrganic chemistryInflammation

Abstract

fetched live from OpenAlex

The kinetics and mechanism of action of the most intensively studied mammalian peroxidases, myeloperoxidase and prostaglandin H synthase are critically reviewed. Evidence against currently favored mechanisms is presented. It is shown that myeloperoxidase has a strong defence mechanism against free hypochlorous acid, commonly thought to be its principal product in its bactericidal activity. Rather, after its two-electron oxidation of chloride ion, myeloperoxidase rapidly converts it into an enzyme-bound chlorinating intermediate, most likely a chlorinated distal imidazole ring. This species chlorinates taurine which may either be a transfer agent of Cl + to other species or may act directly in attack on invading microorganisms. The currently favored mechanism of action of prostaglandin H synthase-1 is a branching chain mechanism in which Compound I is converted into a species containing a tyrosyl radical on the opposite side of the enzyme. Once the tyrosyl radical is formed it converts arachidonic acid into a peroxide in a cyclooxygenase reaction, independent of the peroxidase activity. This mechanism cannot explain the enhancing effect of small free radical scavengers, nor the fact that peroxidase activity continues unabated while the cyclooxygenase reaction is proceeding, nor the 2: 1 ratio of small free radical scavenger to arachidonic acid consumption. A tightly coupling of peroxidase and cycloxygenase reactions appears to be the steady state mechanism, and the branching chain mechanism, if it occurs, is confined to a burst transient state phase.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.171
Threshold uncertainty score0.705

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.013
GPT teacher head0.269
Teacher spread0.256 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2005
Admission routes1
Has abstractyes

Explore more

Same venueProgress in Reaction Kinetics and MechanismSame topicInflammatory mediators and NSAID effectsFrench-language works237,207