Related Experiment Video
Updated: Jun 14, 2026

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
Cytochrome P450: the active oxidant and its spectrum
Jonathan Rittle1, Jarod M Younker, Michael T Green
1Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Inorganic Chemistry
|April 13, 2010
Summary
Laser flash photolysis (LFP) does not quantitatively generate P450 compound I (P450-I). The LFP-generated intermediate
Area of Science:
- Biochemistry
- Enzymology
- Chemical Kinetics
Background:
- Cytochrome P450 enzymes catalyze crucial oxidative reactions.
- The identity of the active oxidizing intermediate, P450 compound I (P450-I), remains debated.
- Recent studies suggest laser flash photolysis (LFP) generates P450-I quantitatively.
Purpose of the Study:
- To evaluate claims that LFP-generated intermediates are P450-I.
- To determine the spectral characteristics of P450-I.
- To compare the LFP-generated intermediate's spectrum with that of P450-I.
Main Methods:
- Analysis of UV/visible spectra.
- Singular value decomposition and target testing on stopped-flow kinetic data.
- Reaction of P450 with m-chloroperbenzoic acid.
Main Results:
- The spectrum of P450-I was obtained in a model-independent manner.
- The UV/visible spectrum of the LFP-generated intermediate showed no similarity to the P450-I spectrum.
- Kinetic analyses suggesting P450-I is not the active oxidant were re-evaluated.
Conclusions:
- The intermediate generated by LFP is not P450 compound I.
- This finding challenges recent interpretations of P450 catalysis mechanisms.
- Further research is needed to elucidate the true nature of the P450 oxidizing intermediate.
Related Concept Videos
Oxidation of Phenols to Quinones
In the presence of oxidizing agents, phenols are oxidized to quinones. Quinones can be easily reduced back to phenols using mild reducing agents. The electron-donating hydroxyl group enhances the reactivity of the aromatic ring, enabling oxidation of the ring even in the absence of an α hydrogen.
o-hydroxy phenols are oxidized to o-quinones and p-hydroxy phenols to p-quinones. Such redox reactions involve the transfer of two electrons and two protons. The reversible redox property is crucial in...
o-hydroxy phenols are oxidized to o-quinones and p-hydroxy phenols to p-quinones. Such redox reactions involve the transfer of two electrons and two protons. The reversible redox property is crucial in...
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,...
Electron Transport Chain: Complex III and IV
During the electron transport chain, electrons from NADH and FADH2 are first transferred to complexes I and II, respectively. These two complexes then transfer the electrons to ubiquinol, which carries them further to complex III. Complex III passes the electrons across the intermembrane space to Cyt c, which carries them further to complex IV. Complex IV donates electrons to oxygen and reduces it to water. As electrons pass through complexes I, III, and IV, the energy released aids the pumping...
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...
Peroxisomes
Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
Peroxisomes
Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
![[(DPEPhos)(bcp)Cu]PF6: A General and Broadly Applicable Copper-Based Photoredox Catalyst](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F59739.jpg&w=3840&q=50)
![Protein Film Infrared Electrochemistry Demonstrated for Study of H2 Oxidation by a [NiFe] Hydrogenase](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F55858.jpg&w=3840&q=50)