Adenosine kinase: An epigenetic modulator in development and disease

Madhuvika Murugan, Denise Fedele, David Millner, Enmar Alharfoush, Geetasravya Vegunta, Detlev Boison

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Adenosine kinase (ADK) is the key regulator of adenosine and catalyzes the metabolism of adenosine to 5′-adenosine monophosphate. The enzyme exists in two isoforms: a long isoform (ADK-long, ADK-L) and a short isoform (ADK-short, ADK-S). The two isoforms are developmentally regulated and are differentially expressed in distinct subcellular compartments with ADK-L localized in the nucleus and ADK-S localized in the cytoplasm. The nuclear localization of ADK-L and its biochemical link to the transmethylation pathway suggest a specific role for gene regulation via epigenetic mechanisms. Recent evidence reveals an adenosine receptor-independent role of ADK in determining the global methylation status of DNA and thereby contributing to epigenomic regulation. Here we summarize recent progress in understanding the biochemical interactions between adenosine metabolism by ADK-L and epigenetic modifications linked to transmethylation reactions. This review will provide a comprehensive overview of ADK-associated changes in DNA methylation in developmental, as well as in pathological conditions including brain injury, epilepsy, vascular diseases, cancer, and diabetes. Challenges in investigating the epigenetic role of ADK for therapeutic gains are briefly discussed.

Original languageEnglish (US)
Article number105054
JournalNeurochemistry International
StatePublished - Jul 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Cell Biology


  • Adenosine kinase
  • DNA methylation
  • Development
  • Epigenetic regulator
  • Epilepsy


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