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

Enzymes02:34

Enzymes

Inside living organisms, enzymes act as catalysts for many biochemical reactions involved in cellular metabolism. The role of enzymes is to reduce the activation energies of biochemical reactions by forming complexes with its substrates. The lowering of activation energies favor an increase in the rates of biochemical reactions.
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
Introduction to Mechanisms of Enzyme Catalysis01:13

Introduction to Mechanisms of Enzyme Catalysis

For many years, scientists thought that enzyme-substrate binding took place in a simple "lock-and-key" fashion. This model stated that the enzyme and substrate fit together perfectly in one instantaneous step. However, current research supports a more refined view scientists call induced fit. The induced-fit model expands upon the lock-and-key model by describing a more dynamic interaction between enzyme and substrate. As the enzyme and substrate come together, their interaction causes a mild...
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 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,...
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence the...
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...

You might also read

Related Articles

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

Sort by
Same author

Simplified approaches to kinetic isotope effects in cytochrome P450-catalyzed reactions and relevance to deuterated drugs.

Drug metabolism reviews·2026
Same author

Response to Mr. DiNardo's "Letter to the Editor: Comprehensive review of octocrylene toxicology data and human exposure assessment for personal care products".

Critical reviews in toxicology·2026
Same author

Interaction of Cytochrome P450 3A4 with Fatty Acid Binding Protein 1 and Relevance to Drug Metabolism.

Journal of medicinal chemistry·2026
Same author

FEMA GRAS assessment of natural flavor complexes: Vanilla extract, Bitter almond oil, Wintergreen oil and related flavoring ingredients.

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association·2026
Same author

Comprehensive review of octocrylene toxicology data and human exposure assessment for personal care products.

Critical reviews in toxicology·2026
Same author

FEMA GRAS assessment of natural flavor complexes: Pepper, ginger, coniferous-derived and related flavoring ingredients.

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association·2025
Same journal

Whole-body mass spectrometry imaging reveals metabolome and lipid peroxidation heterogeneity in zebrafish xenografts of esophageal squamous cell carcinoma.

Analytical and bioanalytical chemistry·2026
Same journal

A robust and validated method for the determination of 21 urinary metabolites of 15 plasticizers, including phthalates, DEHTP, and DINCH, by online SPE and liquid chromatography-tandem mass spectrometry.

Analytical and bioanalytical chemistry·2026
Same journal

A label-free membrane-based biosensor array with AuNP-modified PDMS for sensitive and specific detection of alpha-fetoprotein.

Analytical and bioanalytical chemistry·2026
Same journal

Smartphone-integrated one-step colorimetric glucose detection at physiological pH enabled by a haloperoxidase mimic.

Analytical and bioanalytical chemistry·2026
Same journal

Chemiluminescence functionalized magnetic nanoparticles-based biosensor for sensitive detection of glucose, uric acid, and cholesterol.

Analytical and bioanalytical chemistry·2026
Same journal

Single-cell mass spectrometry imaging: platform advances for multimodal spatial omics.

Analytical and bioanalytical chemistry·2026
See all related articles

Related Experiment Video

Updated: Jul 3, 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

Substrate binding to cytochromes P450.

Emre M Isin1, F Peter Guengerich

  • 1Biotransformation Section, Department of Discovery DMPK & Bioanalytical Chemistry, AstraZeneca R & D Mölndal, 431 83, Mölndal, Sweden. emre.isin@astrazeneca.com

Analytical and Bioanalytical Chemistry
|July 16, 2008
PubMed
Summary
This summary is machine-generated.

This review summarizes over 40 years of research on substrate binding to cytochrome P450 enzymes (P450s). It highlights various biochemical and biophysical techniques used to understand P450 oxidation mechanisms and active-site features.

More Related Videos

Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures
10:44

Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures

Published on: March 28, 2017

Related Experiment Videos

Last Updated: Jul 3, 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

Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures
10:44

Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures

Published on: March 28, 2017

Area of Science:

  • Biochemistry
  • Enzymology
  • Chemical Kinetics

Background:

  • Cytochrome P450 enzymes (P450s) are crucial for metabolizing drugs and endogenous compounds.
  • P450s catalyze the oxidation of unactivated C-H bonds, a unique and challenging reaction.
  • Substrate binding is the initial and critical step in the P450 catalytic cycle.

Purpose of the Study:

  • To review and categorize substrate binding studies of P450 enzymes.
  • To provide insights into the diverse techniques used to investigate P450-substrate interactions.
  • To summarize key findings regarding P450 oxidation mechanisms, substrate properties, and active-site characteristics.

Main Methods:

  • Biochemical assays to study enzyme kinetics and binding affinities.
  • Biophysical techniques such as spectroscopy and calorimetry.
  • Structural biology approaches to elucidate active-site features.

Main Results:

  • Over 40 years of research on P450 substrate binding have been compiled.
  • Studies reveal complex relationships between substrate properties and P450 activity.
  • Diverse methodologies have successfully characterized P450 active sites and catalytic mechanisms.

Conclusions:

  • Substrate binding is a key determinant of P450 function and specificity.
  • A comprehensive understanding of P450s requires integrating data from various biochemical and biophysical studies.
  • Continued investigation into P450-substrate interactions is vital for drug development and understanding biological processes.