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

Decrease in S-adenosylmethionine synthesis by 6-mercaptopurine and methylmercaptopurine ribonucleoside in Molt F4

E H Stet1, R A De Abreu, J P Bökkerink

  • 1Department of Pediatrics, St. Radboud University Hospital of Nijmegen, The Netherlands.

The Biochemical Journal
|November 15, 1994
PubMed
Summary

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

Cysteamine revisited: repair of arginine to cysteine mutations.

Journal of inherited metabolic disease·2017
Same author

MRI and (1)H-MRS in adenosine kinase deficiency.

Neuroradiology·2016
Same author

Physical Fitness, Activity and Hand-Grip Strength Are Not Associated with Arterial Stiffness in Older Individuals.

The journal of nutrition, health & aging·2015
Same author

Arterial stiffness is not associated with bone parameters in an elderly hyperhomocysteinemic population.

Journal of bone and mineral metabolism·2015
Same author

Life-threatening complications of ibogaine: three case reports.

The Netherlands journal of medicine·2012
Same author

Homocysteine and the risk of nursing home admission and mortality in older persons.

European journal of clinical nutrition·2011

6-Mercaptopurine (6-MP) and methylmercaptopurine ribonucleoside (Me-MPR) decrease S-adenosylmethionine (S-Ado-Met) levels by inhibiting purine synthesis. This impacts cellular methylation, potentially contributing to their cytotoxic effects.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • 6-Mercaptopurine (6-MP) and methylmercaptopurine ribonucleoside (Me-MPR) are purine antimetabolites.
  • Both drugs are metabolized to methylthio-IMP (Me-tIMP), a potent inhibitor of de novo purine synthesis.
  • S-adenosylmethionine (S-Ado-Met) is a crucial methyl donor for various cellular macromolecules.

Purpose of the Study:

  • To investigate the effects of 6-MP and Me-MPR on intracellular concentrations of S-Ado-Met, S-adenosylhomocysteine (S-Ado-Hcy), homocysteine, and methionine.
  • To elucidate the impact of these purine antimetabolites on cellular methylation status.
  • To explore potential mechanisms of cytotoxicity related to altered methylation.

Main Methods:

  • Measurement of S-Ado-Met, S-Ado-Hcy, homocysteine, and methionine concentrations in Molt F4 human malignant lymphoblasts.

Related Experiment Videos

  • Analysis of the metabolic pathways involving 6-MP, Me-MPR, and S-Ado-Met.
  • Assessment of ATP levels and their correlation with S-Ado-Met synthesis.

    • Main Results:

    • Both 6-MP and Me-MPR significantly decreased intracellular S-Ado-Met concentrations.
    • A notable increase in S-Ado-Hcy and methionine levels was observed following drug treatment.
    • The observed effects were linked to ATP depletion, inhibiting methionine adenosyltransferase activity and thus S-Ado-Met formation.

    Conclusions:

    • 6-MP and Me-MPR disrupt the cellular methylation balance by depleting S-Ado-Met.
    • This depletion is a consequence of inhibited purine synthesis leading to ATP depletion.
    • Altered cellular methylation may represent an additional mechanism contributing to the cytotoxicity of these purine antimetabolites.