Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Drug Metabolism: Phase I Reactions01:17

Drug Metabolism: Phase I Reactions

A phase I reaction is a biochemical process that introduces a functionally reactive polar group to a substance. This transformation predominantly occurs in the liver, facilitated by the cytochrome P450 system of hemoproteins situated in the lipophilic endoplasmic reticulum of cells. The metabolite generated through this process can have varying polarities. If it is sufficiently polar, it can be easily excreted in the urine due to its water compatibility. However, if the metabolite is nonpolar,...
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes01:28

Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes

Cytochrome P450 (CYP450) enzymes are a superfamily of heme-containing monooxygenases that play a pivotal role in Phase I drug metabolism by catalyzing oxidation and reduction reactions.These enzymes transform lipophilic xenobiotics into more hydrophilic metabolites, facilitating subsequent Phase II conjugation and eventual excretion. The CYP450 family is classified into families (e.g., CYP1–CYP3) and subfamilies (e.g., CYP2A, CYP2C), based on amino acid sequence homology.CYP450 isoenzymes,...
Drug Metabolism: Phase II Reactions01:14

Drug Metabolism: Phase II Reactions

Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...
Bioactivation and Tissue Toxicity01:25

Bioactivation and Tissue Toxicity

Bioactivation is a metabolic process that transforms less reactive substances into highly reactive metabolites, initiating tissue toxicity. This transformation can lead to various toxic effects, including carcinogenesis and teratogenesis. Reactive metabolites are classified into two main types: electrophiles and free radicals.Electrophiles are electron-deficient species and are produced primarily by the enzyme cytochrome P-450 during the metabolism of compounds containing carbon, nitrogen, or...
Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems01:19

Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems

Phase I biotransformation reactions are integral to drug metabolism, predominantly involving oxidative, reductive, and hydrolytic transformations. Chief among these are oxidative reactions, which enhance the hydrophilicity of xenobiotics and introduce polar functional groups to facilitate their elimination from the body.
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance01:07

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance

Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion, mediated...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Strategies for Data-Driven Investigations of Disease and Decreased Production on Stocker Operations.

The Veterinary clinics of North America. Food animal practice·2026
Same author

Stocker Production Medicine: An Emerging Area of Specialization in Modern Food Animal Practice.

The Veterinary clinics of North America. Food animal practice·2026
Same author

Detection and Genomic Characterization of Novel Respiratory Viruses in US and Mexican Cattle Farms.

Transboundary and emerging diseases·2026
Same author

A Systems Perspective on Developing and Improving Data Infrastructure on Stocker Cattle Operations.

The Veterinary clinics of North America. Food animal practice·2026
Same author

Engineering auxin degradation into root-associated bacteria promotes plant growth.

bioRxiv : the preprint server for biology·2025
Same author

Oleoyl coenzyme A triggers peroxygenase activity in cytochrome c.

Journal of inorganic biochemistry·2025
Same journal

Carbonylative Aminative Suzuki-Miyaura Coupling: Pd-Catalyzed Synthesis of Amides from Vinyl/Aryl Halides and Boronic Acids.

Journal of the American Chemical Society·2026
Same journal

Divergent Asymmetric Synthesis of Glutinosasins A-E.

Journal of the American Chemical Society·2026
Same journal

Ultrastrong Polyketone Hot-Melt Adhesives Enabled by Ni-Catalyzed Carbonylative Polymerization.

Journal of the American Chemical Society·2026
Same journal

Programmable Anomalous Photovoltaics Enabled by Light-Electric Dual-Field Control.

Journal of the American Chemical Society·2026
Same journal

Biomimetic Redox-Mediated Proton Relay in Nanoreactors for Photocatalysis.

Journal of the American Chemical Society·2026
Same journal

The Sulfur Monoxide-Water Complex.

Journal of the American Chemical Society·2026
See all related articles

Related Experiment Video

Updated: Jun 22, 2026

Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
09:33

Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling

Published on: March 20, 2018

A highly reactive p450 model compound I.

Seth R Bell1, John T Groves

  • 1Department of Chemistry, Princeton University, Princeton, New Jersey 08544, USA.

Journal of the American Chemical Society
|June 26, 2009
PubMed
Summary
This summary is machine-generated.

This study details the rapid C-H hydroxylation reactions of a cytochrome P450 model compound I, [OFe(IV)-4-TMPyP](+) (1). The research highlights its extraordinary reaction rates and provides insights into the mechanisms of high reactivity in these important biological catalysts.

More Related Videos

Preparation of SNS Cobalt(II) Pincer Model Complexes of Liver Alcohol Dehydrogenase
06:31

Preparation of SNS Cobalt(II) Pincer Model Complexes of Liver Alcohol Dehydrogenase

Published on: March 19, 2020

High-Throughput Metabolic Profiling for Model Refinements of Microalgae
11:07

High-Throughput Metabolic Profiling for Model Refinements of Microalgae

Published on: December 4, 2021

Related Experiment Videos

Last Updated: Jun 22, 2026

Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
09:33

Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling

Published on: March 20, 2018

Preparation of SNS Cobalt(II) Pincer Model Complexes of Liver Alcohol Dehydrogenase
06:31

Preparation of SNS Cobalt(II) Pincer Model Complexes of Liver Alcohol Dehydrogenase

Published on: March 19, 2020

High-Throughput Metabolic Profiling for Model Refinements of Microalgae
11:07

High-Throughput Metabolic Profiling for Model Refinements of Microalgae

Published on: December 4, 2021

Area of Science:

  • Biochemistry and Biophysical Chemistry
  • Organometallic Chemistry
  • Catalysis

Background:

  • Cytochrome P450 enzymes are crucial for metabolizing a wide range of substrates.
  • Understanding the reactivity of their active site, particularly Compound I, is key to elucidating their biological function.
  • Model compounds are essential for studying the fundamental chemistry of these complex systems.

Purpose of the Study:

  • To detect and kinetically characterize a specific cytochrome P450 Compound I model, [OFe(IV)-4-TMPyP](+) (1).
  • To investigate the reaction rates and mechanisms of C-H hydroxylation mediated by this model compound.
  • To correlate the observed reactivity with electronic and structural properties of the model.

Main Methods:

  • Stopped-flow spectrophotometry to monitor the formation and decay of the intermediate.
  • Nuclear Magnetic Resonance (NMR) spectroscopy (¹H and ¹³C) to identify reaction products.
  • Electrospray ionization mass spectrometry (ESI-MS) to determine oxygen incorporation.
  • Kinetic isotope effect studies using deuterated substrates.

Main Results:

  • The intermediate [OFe(IV)-4-TMPyP](+) (1) was detected with a high second-order rate constant for formation (1.59 x 10⁷ M⁻¹s⁻¹).
  • Compound 1 exhibited extraordinary second-order rate constants for C-H hydroxylation (e.g., 3.6 x 10⁶ M⁻¹s⁻¹ for xanthene).
  • Product analysis and kinetic isotope effects suggest a homolytic hydrogen abstraction mechanism.
  • Oxygen rebound and Brønsted-Evans-Polanyi analysis provided insights into the transition state and bond energies.

Conclusions:

  • The cytochrome P450 model compound I, [OFe(IV)-4-TMPyP](+), displays exceptionally high reactivity in C-H hydroxylation.
  • High porphyrin redox potential and spin-state-crossing phenomena are proposed as origins of this reactivity.
  • Subtle active site modifications can significantly enhance the catalytic efficiency of P450 enzymes.