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Related Concept Videos

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,...
Pharmacogenetics of Drug Metabolism: Overview01:27

Pharmacogenetics of Drug Metabolism: Overview

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...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
Drug toxicity: Idiosyncratic Reactions01:16

Drug toxicity: Idiosyncratic Reactions

Idiosyncratic drug reactions represent abnormal chemical responses that vary significantly among individuals, ranging from extreme sensitivity to low doses to insensitivity to high doses. These reactions often occur due to the drug's covalent binding with serum proteins, forming a foreign hapten that triggers an immunotoxicological response. The variability in drug reactions has a strong pharmacogenetic foundation, with genetic differences crucial in how individuals metabolize drugs. For...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Principles of Pharmacogenetics: Types of Genetic Variants01:27

Principles of Pharmacogenetics: Types of Genetic Variants

The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...

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Related Experiment Video

Updated: Jun 15, 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

Human CYP2C8: structure, substrate specificity, inhibitor selectivity, inducers and polymorphisms.

Xin-Sheng Lai1, Li-Ping Yang, Xiao-Tian Li

  • 1College of Acupuncture and Massage, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.

Current Drug Metabolism
|March 11, 2010
PubMed
Summary
This summary is machine-generated.

Human Cytochrome P450 2C8 (CYP2C8) metabolizes many drugs and endogenous compounds. Its active site structure allows binding of diverse substrates, impacting drug interactions and clearance.

Related Experiment Videos

Last Updated: Jun 15, 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

Area of Science:

  • Biochemistry
  • Pharmacology
  • Enzymology

Background:

  • Human Cytochrome P450 2C8 (CYP2C8) is a crucial enzyme in the CYP2C subfamily.
  • It plays a significant role in metabolizing over 60 clinical drugs and endogenous compounds like retinoids and arachidonic acid.

Purpose of the Study:

  • To elucidate the structural and functional characteristics of the human CYP2C8 enzyme.
  • To understand its substrate binding capabilities and implications for drug metabolism and interactions.

Main Methods:

  • Homology modeling and site-directed mutagenesis studies to identify active site residues.
  • Structural analysis of CYP2C8 in complex with various ligands.
  • Review of known CYP2C8 substrates, inhibitors, and regulatory pathways.

Main Results:

  • CYP2C8 possesses a large, trifurcated active site cavity, accommodating large substrates like paclitaxel.
  • The enzyme binds diverse substrates and inhibitors without significant conformational changes.
  • Key drugs metabolized by CYP2C8 include paclitaxel, amodiaquine, and ibuprofen; it also metabolizes endogenous retinoids and arachidonic acid.

Conclusions:

  • CYP2C8's structural features enable the metabolism of a wide array of drugs and endogenous molecules.
  • Inhibition of CYP2C8 can lead to significant clinical drug interactions.
  • Genetic variations in CYP2C8 influence drug clearance, highlighting its importance in personalized medicine and drug development.