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Related Concept Videos

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...
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

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...
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 II Reactions01:14

Drug Metabolism: Phase II Reactions

Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...
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,...
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...

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Updated: Jun 3, 2026

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform
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Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform

Published on: May 10, 2024

5-Fluorouracil metabolizing enzymes.

H L McLeod1, L H Milne, S J Johnston

  • 1Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK.

Methods in Molecular Medicine
|March 5, 2011
PubMed
Summary
This summary is machine-generated.

Dihydropyrimidine dehydrogenase (DPD) significantly metabolizes 5-fluorouracil (5-FU), an active chemotherapy drug. Understanding DPD

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Area of Science:

  • Oncology
  • Pharmacology
  • Biochemistry

Background:

  • 5-fluorouracil (5-FU) is a uracil analog used in treating various cancers, including breast, head/neck, gastrointestinal, and colorectal malignancies.
  • 5-FU requires intracellular conversion to active cytotoxic nucleotides to exert its therapeutic effect.
  • Key mechanisms of 5-FU action involve thymidylate synthase (TS) inhibition and incorporation into RNA/DNA, but cellular resistance factors are not fully understood.

Purpose of the Study:

  • To investigate the role of dihydropyrimidine dehydrogenase (DPD) in 5-FU metabolism and its impact on drug activity.
  • To highlight the significance of DPD as the rate-limiting enzyme in the primary catabolic pathway of 5-FU.

Main Methods:

  • Review of existing literature on 5-FU metabolism and resistance mechanisms.
  • Analysis of studies utilizing (19)F nuclear magnetic resonance (NMR) spectroscopy in preclinical models.

Main Results:

  • The majority of administered 5-FU is metabolized into inactive species by a three-enzyme process initiated by DPD.
  • DPD is responsible for the degradation of approximately 80% of 5-FU within 24 hours post-administration.
  • In preclinical tumor models, catabolites of 5-FU constituted a significant portion (51%) of the drug detected, compared to anabolic products (26%).

Conclusions:

  • DPD-mediated metabolism is a critical factor in the pharmacokinetics and efficacy of 5-FU.
  • The substantial catabolism of 5-FU by DPD suggests it as a key determinant of drug availability and potential resistance.
  • Further research into DPD activity could lead to improved 5-FU therapeutic strategies and personalized treatment approaches.