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

Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes01:28

Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes

163
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...
163
Pharmacokinetics: Drug–Drug Interactions01:25

Pharmacokinetics: Drug–Drug Interactions

675
Drug interactions occur when the pharmacological effect of one drug is altered by another substance, either enhancing or diminishing its activity. The drug whose activity is altered is known as the object drug, and the substance causing the alteration is called the agent drug or the precipitant. The net effects of these interactions are mostly undesirable, leading to decreased effectiveness or increased adverse effects. In rare cases, interactions can be beneficial, such as the enhanced...
675
Pharmacogenetics of Drug Metabolism: Overview01:27

Pharmacogenetics of Drug Metabolism: Overview

117
Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...
117
Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry01:20

Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry

666
Orally administered drugs primarily enter the systemic circulation via passive diffusion through the intestinal membranes. The drug's absorption is influenced by drug stability in the gastrointestinal GI tract, membrane permeability, the surface area available for absorption, luminal drug concentration, and residence time in the lumen. Drug permeability can be enhanced by adjusting the lipophilicity, polarity, or molecular size of the drug, promoting its passive transport across intestinal...
666
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

64
Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
64
Factors Affecting Drug Biotransformation: Physicochemical and Chemical Properties of Drugs01:21

Factors Affecting Drug Biotransformation: Physicochemical and Chemical Properties of Drugs

941
A drug's physicochemical properties fundamentally influence its metabolism. For instance, a drug's molecular size and shape critically determine its interaction with enzymes and transporters — larger drugs may face difficulty reaching enzyme active sites, altering their metabolic pathways. The pKa of a drug, which establishes its ionization state, can impact its solubility and absorption, thereby influencing metabolism.
The drug's acidity or basicity is essential in...
941

You might also read

Related Articles

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

Sort by
Same author

MASLD Is Associated With Decreased General Health Perception, Quality of Life and Work Productivity in a Low Fibrosis Population.

Liver international : official journal of the International Association for the Study of the Liver·2026
Same author

A long-term study of liver-related events in Caucasian hepatitis B patients with normal ALT values and high viremia.

Acta gastro-enterologica Belgica·2022
Same author

Gastrointestinal digestion of dietary advanced glycation endproducts increases their pro-inflammatory potential.

Food & function·2021
Same author

[Non-alcoholic fatty liver disease; a full-bodied epidemic].

Nederlands tijdschrift voor geneeskunde·2020
Same author

Ranking Self-reported Gastrointestinal Side Effects of Pharmacotherapy in Sarcoidosis.

Lung·2020
Same author

Placenta derived factors involved in the pathogenesis of the liver in the syndrome of haemolysis, elevated liver enzymes and low platelets (HELLP): A review.

Pregnancy hypertension·2019

Related Experiment Video

Updated: Apr 1, 2026

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

10.4K

Chemical characteristics for optimizing CYP2E1 inhibition.

B van de Wier1, J M Balk1, A Bast1

  • 1Department of Toxicology, P.O. Box 616, 6200 MD, Maastricht, Maastricht University, The Netherlands.

Chemico-Biological Interactions
|October 3, 2015
PubMed
Summary
This summary is machine-generated.

Researchers identified key chemical properties for inhibiting Cytochrome P450 2E1 (CYP2E1). Optimal inhibition of CYP2E1, linked to liver diseases like NASH and ASH, depends mainly on lipophilicity, with a specific log D7.4 value.

Keywords:
Alcoholic liver diseaseCytochrome P450 2E1Nonalcoholic liver diseaseTopliss

More Related Videos

Efficient Purification and LC-MS/MS-based Assay Development for Ten-Eleven Translocation-2 5-Methylcytosine Dioxygenase
10:33

Efficient Purification and LC-MS/MS-based Assay Development for Ten-Eleven Translocation-2 5-Methylcytosine Dioxygenase

Published on: October 15, 2018

8.7K
Unveiling Xenobiotic Transport and Effects in Isolated Mitochondria: Insights from Respirometric and Enzymatic Assays
08:03

Unveiling Xenobiotic Transport and Effects in Isolated Mitochondria: Insights from Respirometric and Enzymatic Assays

Published on: March 7, 2025

1.0K

Related Experiment Videos

Last Updated: Apr 1, 2026

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

10.4K
Efficient Purification and LC-MS/MS-based Assay Development for Ten-Eleven Translocation-2 5-Methylcytosine Dioxygenase
10:33

Efficient Purification and LC-MS/MS-based Assay Development for Ten-Eleven Translocation-2 5-Methylcytosine Dioxygenase

Published on: October 15, 2018

8.7K
Unveiling Xenobiotic Transport and Effects in Isolated Mitochondria: Insights from Respirometric and Enzymatic Assays
08:03

Unveiling Xenobiotic Transport and Effects in Isolated Mitochondria: Insights from Respirometric and Enzymatic Assays

Published on: March 7, 2025

1.0K

Area of Science:

  • Hepatology and Pharmacology
  • Enzyme Kinetics and Drug Discovery

Background:

  • Cytochrome P450 2E1 (CYP2E1) activity correlates with liver damage in alcoholic steatohepatitis (ASH) and non-alcoholic steatohepatitis (NASH).
  • CYP2E1 generates reactive oxygen species (ROS) and toxic metabolites, contributing to oxidative stress and liver injury in these conditions.

Purpose of the Study:

  • To determine the essential chemical characteristics of compounds that effectively inhibit CYP2E1.
  • To guide the development of novel therapeutic agents for CYP2E1-associated liver diseases.

Main Methods:

  • Tested structurally related analogs varying in lipophilic, steric, and electronic properties.
  • Evaluated homologous series of alcohols, aldehydes, ketones, and carboxylic acids for CYP2E1 inhibitory potential.

Main Results:

  • Inhibition of CYP2E1 activity is predominantly influenced by lipophilicity.
  • An optimal log D7.4 (octanol/water distribution coefficient at pH 7.4) of approximately 2.4 was identified for CYP2E1 inhibition.
  • For carboxylic acids, interactions with polar residues in the active site are also crucial for inhibition.

Conclusions:

  • Lipophilicity is a primary determinant for CYP2E1 inhibitors.
  • Understanding these chemical prerequisites aids in discovering new treatments for ASH and NASH.
  • This research provides foundational insights for developing therapeutic strategies targeting CYP2E1-mediated liver damage.