Multiple oxidants have been implicated as playing a role in cytochrome P450-mediated oxidations. Herein, we report results on N-dealkylation, one of the most facile reactions mediated by P450 enzymes. We have employed the N-oxides of a series of para-substituted 13C2H2-labeled N,N-dimethylanilines to function as both substrates and surrogate oxygen atom donors for P450cam and P4502E1. Kinetic isotope effect profiles obtained using the N-oxide system were found to closely match the profiles produced using the complete NAD(P)H/NAD(P)-P450 reductase/O2 system. The results are consistent with oxidation occurring solely through an iron-oxene species.
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http://dx.doi.org/10.1021/ja0486364 | DOI Listing |
Nat Commun
January 2025
Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul, 03722, Republic of Korea.
1,4-Azaborine-based arenes are promising electroluminescent emitters with thermally activated delayed fluorescence (TADF), offering narrow emission spectra and high quantum yields due to a multi-resonance (MR) effect. However, their practical application is constrained by their limited operational stability. This study investigates the degradation mechanism of MR-TADF molecules.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Dementia Research Centre, UCL Queen Square Institute of Neurology, London, United Kingdom.
Background: Knowledge of the chemical composition of amyloid plaques and tau tangles at the earlier stages of Alzheimer's disease (AD) pathology is sparse. This is due to limited access to human brain during life and at the earlier stages of AD pathophysiology and technical limitations in quantifying amyloid and tau species at a subcellular level. Understanding the chemical composition of plaques and tangles, how rapidly they grow and what factors drive growth is important for developing and refining therapeutics.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Université de Montpellier, Montpellier, France.
Background: Protein metabolism and turnover can be monitored using tracer methods, notably stable isotope labeling kinetics (SILK) based on 13C-leucine incorporation. This approach has been used in Alzheimer's disease, specifically analyzing the turnover in cerebrospinal fluid of biomarkers of interest, including amyloid peptides, leading to major pathophysiological insights (Nature medicine 12:856-861). This was achieved using immunoprecipitation mass spectrometry, which enables to track a small number of targets present in low concentration.
View Article and Find Full Text PDFEnviron Sci Technol
December 2024
Key Laboratory of Atmospheric Environment and Extreme Meteorology, Institute of Atmospheric Physics, Chinese Academy of Sciences, Beijing 100029, China.
Aerosol ammonium (NH) is a critical component of particulate matter that affects air pollution, climate, and human health. Isotope-based source apportionment of NH is essential for ammonia (NH) mitigation but the role of kinetic vs equilibrium controls on nitrogen isotope (δN) fractionation between NH and NH remains unresolved. Based on concurrent measurements of NH and NH in winter Beijing, we observed that the difference of δN between NH and NH on clean days (3.
View Article and Find Full Text PDFJ Nutr
December 2024
Department of Geriatrics, Donald W. Reynolds Institute on Aging, Center for Translational Research in Aging & Longevity, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Background: Reduced meal frequency patterns have become popular for weight loss, maintenance, and improving cardiometabolic health. The extended fasting windows with these dietary patterns could lead to greater protein breakdown, which is a concern for middle-age and older adults who may need higher protein intakes to maintain or increase net protein balance.
Objective: The purpose of this study was to quantify muscle and whole-body protein kinetic responses to three different daily protein intakes within a two-meal eating pattern.
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