Related Experiment Video

Updated: Oct 1, 2026

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
08:59

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

Published on: December 3, 2020

Molecular mechanisms of polymorphic CYP3A7 expression in adult human liver and intestine

Oliver Burk1, Heike Tegude, Ina Koch

  • 1Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, D-70376 Stuttgart, Germany. oliver.burk@ikp-stuttgart.de

The Journal of Biological Chemistry
|April 10, 2002
PubMed

Insights

The CYP3A7*1C genetic variant increases drug metabolism by enhancing CYP3A7 gene expression in the liver and intestine. This is due to a CYP3A4 promoter region, impacting drug efficacy.

Area of Science:

  • Pharmacogenomics
  • Drug Metabolism
  • Molecular Biology

Background:

  • Human CYP3A enzymes are crucial for drug metabolism, with individual expression variability affecting treatment outcomes.
  • The specific roles of the four CYP3A genes in overall CYP3A activity are not fully understood.

Purpose of the Study:

  • To investigate the expression of CYP3A7 in human liver and intestine.
  • To clarify the contribution of CYP3A7 to total CYP3A activity and its genetic regulation.

Main Methods:

  • Studied CYP3A7 mRNA expression in human liver and intestine tissues.
  • Analyzed the association of CYP3A7 alleles (*1C and *1B) with gene expression levels.
  • Investigated the role of the ER6 motif and receptor binding in CYP3A7 promoter activity.

Main Results:

  • CYP3A7 mRNA expression was found to be polymorphic in both liver and intestine.
  • The CYP3A7*1C allele strongly correlated with increased CYP3A7 expression in both organs.
  • The CYP3A7*1B allele was linked to higher CYP3A7 expression solely in the liver.
  • The CYP3A7*1C allele contains a CYP3A4-derived ER6 motif, which binds nuclear receptors more effectively, driving higher CYP3A7 expression.

Conclusions:

  • The presence of the CYP3A4-derived ER6 motif in the CYP3A7*1C allele is responsible for the elevated CYP3A7 expression observed in individuals carrying this allele.
  • This finding helps explain inter-individual variability in drug metabolism and response.

More Related Videos

Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures10:44

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

Published on: March 28, 2017

Human Liver Spheroids from Peripheral Blood for Liver Disease Studies09:51

Human Liver Spheroids from Peripheral Blood for Liver Disease Studies

Published on: January 27, 2023

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 Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
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...
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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...
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...