scholarly journals Hydrogen Atom vs. Hydride Transfer in Cytochrome P450 Oxidations: A Combined Mass Spectrometry and Computational Study

2018 ◽  
Vol 2018 (17) ◽  
pp. 1854-1865 ◽  
Author(s):  
Fabián G. Cantú Reinhard ◽  
Simonetta Fornarini ◽  
Maria Elisa Crestoni ◽  
Sam P. de Visser
Keyword(s):  
Mass Spectrometry ◽  
Cytochrome P450 ◽  
Hydrogen Atom ◽  
Computational Study ◽  
Hydride Transfer

scholarly journals A Systematic Account on Aromatic Hydroxylation by a Cytochrome P450 Model Compound I: A Low-Pressure Mass Spectrometry and Computational Study

2016 ◽  
Vol 22 (51) ◽  
pp. 18608-18619 ◽  
Author(s):  
Fabián G. Cantú Reinhard ◽  
Mala A. Sainna ◽  
Pranav Upadhyay ◽  
G. Alex Balan ◽  
Devesh Kumar ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cytochrome P450 ◽  
Model Compound ◽  
Computational Study ◽  
Low Pressure ◽  
Compound I ◽  
Systematic Account ◽  
Aromatic Hydroxylation

2-Deoxyribose Radicals in the Gas Phase and Aqueous Solution. Transient Intermediates of Hydrogen Atom Abstraction from 2-Deoxyribofuranose

2005 ◽  
Vol 70 (11) ◽  
pp. 1769-1786 ◽  
Author(s):  
Luc A. Vannier ◽  
Chunxiang Yao ◽  
František Tureček
Keyword(s):  
Aqueous Solution ◽  
Hydrogen Atom ◽  
Gas Phase ◽  
Computational Study ◽  
Hydrogen Atom Abstraction ◽  
Oh Radical ◽  
Free Energies ◽  
Intramolecular Hydrogen ◽  
Solvation Free Energies ◽  
Transient Intermediates

A computational study at correlated levels of theory is reported to address the structures and energetics of transient radicals produced by hydrogen atom abstraction from C-1, C-2, C-3, C-4, C-5, O-1, O-3, and O-5 positions in 2-deoxyribofuranose in the gas phase and in aqueous solution. In general, the carbon-centered radicals are found to be thermodynamically and kinetically more stable than the oxygen-centered ones. The most stable gas-phase radical, 2-deoxyribofuranos-5-yl (5), is produced by H-atom abstraction from C-5 and stabilized by an intramolecular hydrogen bond between the O-5 hydroxy group and O-1. The order of radical stabilities is altered in aqueous solution due to different solvation free energies. These prefer conformers that lack intramolecular hydrogen bonds and expose O-H bonds to the solvent. Carbon-centered deoxyribose radicals can undergo competitive dissociations by loss of H atoms, OH radical, or by ring cleavages that all require threshold dissociation or transition state energies >100 kJ mol-1. This points to largely non-specific dissociations of 2-deoxyribose radicals when produced by exothermic hydrogen atom abstraction from the saccharide molecule. Oxygen-centered 2-deoxyribose radicals show only marginal thermodynamic and kinetic stability and are expected to readily fragment upon formation.

Computational study on the mechanism of hydroboration of CO2 catalysed by POCOP pincer nickel thiolate complexes: concerted catalysis and hydride transfer by a shuttle

2021 ◽  
Vol 50 (8) ◽  
pp. 2903-2914
Author(s):  
Nana Ma ◽  
Chenhao Tu ◽  
Qingli Xu ◽  
Wenyue Guo ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Computational Study ◽  
Hydride Transfer ◽  
Dft Computations ◽  
Thiolate Complexes

The concerted catalysis and hydride shuttle mechanism for pincer nickel thiolate catalysed hydroboration of CO2 was established by DFT computations.

scholarly journals Infrared Photoactivation Reduces Peptide Folding and Hydrogen-Atom Migration following ETD Tandem Mass Spectrometry

2009 ◽  
Vol 48 (45) ◽  
pp. 8526-8528 ◽  
Author(s):  
Aaron R. Ledvina ◽  
Graeme C. McAlister ◽  
Myles W. Gardner ◽  
Suncerae I. Smith ◽  
James A. Madsen ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Hydrogen Atom ◽  
Tandem Mass Spectrometry ◽  
Peptide Folding ◽  
Tandem Mass ◽  
Atom Migration

scholarly journals Exploring the Interactome of Cytochrome P450 2E1 in Human Liver Microsomes with Chemical Cross-Linking Mass Spectrometry

2021 ◽  
Author(s):  
Dmitri R. Davydov ◽  
Bikash Dangi ◽  
Guihua Yue ◽  
Bhagwat Prasad ◽  
Viktor G. Zgoda
Keyword(s):  
Mass Spectrometry ◽  
Cytochrome P450 ◽  
Protein Interactions ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Cross Linking ◽  
Cytochrome P450 2E1 ◽  
Protein Protein Interactions ◽  
Chemical Cross Linking

This study aimed on exploration of the system-wide effects of the alcohol-induced increase in the content of cytochrome P450 2E1 (CYP2E1) in the human liver on drug metabolism. Using membrane incorporation of purified CYP2E1 modified with photoreactive crosslinkers benzophenone-4-maleimide (BPM) and 4-(N-succinimidylcarboxy)benzophenone (BPS), we explored the array of its protein-protein interactions (proteome) in human liver microsomes (HLM) with chemical cross-linking mass spectrometry (CXMS). Exposure of bait-incorporated HLM samples to light was followed by isolation of the His-tagged bait protein and its cross-linked aggregates on Ni-NTA agarose. Analyzing the individual bands of SDS-PAGE slabs of thereby isolated protein with the toolset of untargeted proteomics, we detected the cross-linked dimeric and trimeric complexes of CYP2E1 with other drug-metabolizing enzymes. Among the most extensively cross-linked partners of CYP2E1 are cytochromes P450 2A6, 3A4, 2C9, and 4A11. We also detected the conjugates of CYP2E1 with UDP-glucuronosyltransferases (UGTs) 1A6, 1A9, 2B4, 2B15, and 2B17. These results demonstrate the exploratory power of the proposed CXMS strategy and corroborate the concept of tight functional integration in the human drug-metabolizing ensemble through protein-protein interactions of the constituting enzymes. Of particular interest is the observation of efficient cross-linking of CYP2E1 with CYP4A11. This enzyme plays a central role in the synthesis of vasoactive eicosanoids and its interactions with alcohol-inducible CYP2E1 may shed light on the mechanisms of alcohol-induced hypertension.

Understanding Hydrogen Atom and Hydride Transfer Processes during Electrochemical Alcohol and Aldehyde Oxidation

ACS Catalysis ◽  
2021 ◽  
pp. 15110-15124
Author(s):  
Michael T. Bender ◽  
Robert E. Warburton ◽  
Sharon Hammes-Schiffer ◽  
Kyoung-Shin Choi
Keyword(s):  
Hydrogen Atom ◽  
Hydride Transfer ◽  
Transfer Processes ◽  
Aldehyde Oxidation

scholarly journals Biomarker Discovery for Cytochrome P450 1A2 Activity Assessment in Rats, Based on Metabolomics

Metabolites ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 77 ◽  
Author(s):  
Xiao Pu ◽  
Yiqiao Gao ◽  
Ruiting Li ◽  
Wei Li ◽  
Yuan Tian ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cytochrome P450 ◽  
Biomarker Discovery ◽  
Absolute Quantification ◽  
Pharmacokinetic Analysis ◽  
Large Individual ◽  
Mrna Levels ◽  
Cytochrome P450 1A2 ◽  
Interindividual Variations ◽  
Highly Correlated

Cytochrome P450 1A2 (CYP1A2) is one of the major CYP450 enzymes (CYPs) in the liver, and participates in the biotransformation of various xenobiotics and endogenous signaling molecules. The expression and activity of CYP1A2 show large individual differences, due to genetic and environmental factors. In order to discover non-invasive serum biomarkers associated with hepatic CYP1A2, mass spectrometry-based, untargeted metabolomics were first conducted, in order to dissect the metabolic differences in the serum and liver between control rats and β-naphthoflavone (an inducer of CYP1A2)-treated rats. Real-time reverse transcription polymerase chain reaction and pharmacokinetic analysis of phenacetin and paracetamol were performed, in order to determine the changes of mRNA levels and activity of CYP1A2 in these two groups, respectively. Branched-chain amino acids phenylalanine and tyrosine were ultimately focalized, as they were detected in both the serum and liver with the same trends. These findings were further confirmed by absolute quantification via a liquid chromatography–tandem mass spectrometry (LC-MS/MS)-based targeted metabolomics approach. Furthermore, the ratio of phenylalanine to tyrosine concentration was also found to be highly correlated with CYP1A2 activity and gene expression. This study demonstrates that metabolomics can be a potentially useful tool for biomarker discovery associated with CYPs. Our findings contribute to explaining interindividual variations in CYP1A2-mediated drug metabolism.

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