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 Experiment Videos

Guanethidine N-oxidation in human liver microsomes.

M E McManus1, D S Davies, A R Boobis

  • 1Department of Clinical Pharmacology, School of Medicine, Flinders University, Bedford Park, Australia.

The Journal of Pharmacy and Pharmacology
|December 1, 1987
PubMed
Summary

Guanethidine N-oxidation in human liver microsomes is optimal at pH 8.5. This process can effectively measure flavin-containing monooxygenase activity, showing significant interindividual variability.

Related Concept Videos

You might also read

Related Articles

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

Sort by
Same author

Protein complexes from mouse and chick brain that interact with phospho-KXGS motif tau/microtubule associated protein antibody.

Biology open·2024
Same author

Test and Risk Assessment Strategies for combined exposure to multiple chemicals.

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association·2020
Same author

Overview on legislation and scientific approaches for risk assessment of combined exposure to multiple chemicals: the potential EuroMix contribution.

Critical reviews in toxicology·2019
Same author

Diphtheria in Bristol, 1921.

The Hospital and health review·2018
Same author

On an Outbreak of Milk-Borne Enteric Fever in Clifton, in Relation to Distribution of the Disease, Incidence of Attack, and General Character of the Outbreak; with Some Reference to the Use of the Serum Test (Widal) in Public Health Work.

Transactions. Epidemiological Society of London·2018
Same author

Mortality and Sickness in the City of Bristol for the Year 1903.

Bristol medico-chirurgical journal (1883)·2017

Area of Science:

  • Pharmacology
  • Drug Metabolism
  • Biochemistry

Background:

  • Human liver microsomes are crucial for drug metabolism.
  • Guanethidine is a substrate whose metabolic pathways are of clinical interest.
  • Understanding interindividual variability in drug metabolism is key to personalized medicine.

Purpose of the Study:

  • To assess the capacity of human liver microsomes to N-oxidize guanethidine.
  • To determine the optimal conditions for guanethidine N-oxidation.
  • To evaluate guanethidine N-oxidation as a potential biomarker for flavin-containing monooxygenase (FMO) activity.

Main Methods:

  • Incubation of human liver microsomes (n=25) with guanethidine.
  • Measurement of N-oxidation rates at varying pH (optimal at 8.5, compared to 7.4).

Related Experiment Videos

  • Assessment of inhibition by cytochrome P450 inhibitors (proadifen, DPEA).

    • Main Results:

    • Guanethidine N-oxidation was significantly higher at pH 8.5 (2.46 ± 0.89) compared to pH 7.4 (0.38 ± 0.22).
    • Rates at pH 7.4 were only 16% of the maximal rate observed at pH 8.5.
    • Interindividual variability in N-oxidation rates was substantial (17-fold at pH 8.5, 11-fold at pH 7.4).
    • Cytochrome P450 inhibitors showed minimal impact (<20% reduction) on guanethidine N-oxidation.

    Conclusions:

    • Guanethidine N-oxidation is primarily mediated by FMOs, not cytochrome P450 enzymes.
    • The significant interindividual differences highlight the potential for variable drug response.
    • Guanethidine N-oxidation serves as a reliable index for assessing FMO activity in human liver microsomes.