The lysine degradation pathway: Subcellular compartmentalization and enzyme deficiencies

João Leandro, Sander M. Houten

Research output: Contribution to journalReview articlepeer-review

28 Scopus citations


Lysine degradation via formation of saccharopine is a pathway confined to the mitochondria. The second pathway for lysine degradation, the pipecolic acid pathway, is not yet fully elucidated and known enzymes are localized in the mitochondria, cytosol and peroxisome. The tissue-specific roles of these two pathways are still under investigation. The lysine degradation pathway is clinically relevant due to the occurrence of two severe neurometabolic disorders, pyridoxine-dependent epilepsy (PDE) and glutaric aciduria type 1 (GA1). The existence of three other disorders affecting lysine degradation without apparent clinical consequences opens up the possibility to find alternative therapeutic strategies for PDE and GA1 through pathway modulation. A better understanding of the mechanisms, compartmentalization and interplay between the different enzymes and metabolites involved in lysine degradation is of utmost importance.

Original languageEnglish
Pages (from-to)14-22
Number of pages9
JournalMolecular Genetics and Metabolism
Issue number1-2
StatePublished - 1 Sep 2020


  • Inborn errors
  • Lysine degradation
  • Mitochondria
  • Pipecolic acid pathway
  • Saccharopine pathway
  • Substrate reduction therapy


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