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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,...
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,...
Electron Transport Chain: Complex III and IV01:43

Electron Transport Chain: Complex III and IV

During the electron transport chain, electrons from NADH and FADH2 are first transferred to complexes I and II, respectively. These two complexes then transfer the electrons to ubiquinol, which carries them further to complex III. Complex III passes the electrons across the intermembrane space to Cyt c, which carries them further to complex IV. Complex IV donates electrons to oxygen and reduces it to water. As electrons pass through complexes I, III, and IV, the energy released aids the pumping...
Bioactivation and Tissue Toxicity01:25

Bioactivation and Tissue Toxicity

Bioactivation is a metabolic process that transforms less reactive substances into highly reactive metabolites, initiating tissue toxicity. This transformation can lead to various toxic effects, including carcinogenesis and teratogenesis. Reactive metabolites are classified into two main types: electrophiles and free radicals.Electrophiles are electron-deficient species and are produced primarily by the enzyme cytochrome P-450 during the metabolism of compounds containing carbon, nitrogen, or...
Phase I Oxidative Reactions: Overview01:19

Phase I Oxidative Reactions: Overview

Phase I biotransformation, or functionalization, is a crucial chemical process that converts drugs and other xenobiotics into more water-soluble forms, facilitating expulsion from the body. It involves oxidative, reductive, and hydrolytic reactions that add or unveil polar functional groups on lipophilic substrates. Key players in phase I reactions are the mixed-function oxidases. Situated in liver cell microsomes, these enzymes predominantly carry out drug metabolism. They require molecular...
Peroxisomes01:24

Peroxisomes

Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...

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Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
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Human cytochrome P450 4F3: structure, functions, and prospects.

Laurent Corcos1, Danièle Lucas, Catherine Le Jossic-Corcos

  • 1INSERM U613-ECLA, Faculté de Médecine, Brest, France. laurent.corcos@inserm.fr

Drug Metabolism and Drug Interactions
|June 19, 2012
PubMed
Summary

Cytochrome P450 4F3 (CYP4F3) enzymes metabolize fatty acid epoxides and leukotriene B4. This review highlights CYP4F3 regulation, isoforms (CYP4F3A/B), and roles in diseases like Crohn's.

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Area of Science:

  • Biochemistry
  • Genetics
  • Molecular Biology

Background:

  • Cytochrome P450 4F3 (CYP4F3) is involved in metabolizing endobiotics and xenobiotics.
  • CYP4F3 enzymes catalyze the oxidation of fatty acid epoxides and ω-hydroxylation of leukotriene B4.
  • The CYP4F gene family is located on chromosome 19p13.

Purpose of the Study:

  • To review the regulation and functional roles of human CYP4F3 enzymes.
  • To provide an overview of CYP4F3A and CYP4F3B isoforms.
  • To discuss the implications of CYP4F3 in various pathologies.

Main Methods:

  • Literature review of existing studies on CYP4F3.
  • Analysis of gene expression and alternative splicing mechanisms.
  • Examination of CYP4F3 single nucleotide polymorphisms (SNPs) and associated diseases.

Main Results:

  • CYP4F3 expression yields two isoforms, CYP4F3A (leukocytes) and CYP4F3B (liver), via alternative splicing.
  • CYP4F3 plays a key role in fatty acid epoxide metabolism.
  • CYP4F3 SNPs are linked to celiac and Crohn's diseases.

Conclusions:

  • CYP4F3 enzymes have critical roles in human health and disease.
  • Tissue-specific expression of CYP4F3 isoforms suggests distinct physiological functions.
  • Further research into CYP4F3 is warranted given its association with inflammatory diseases.