@article{93456,
  keywords = {C13orf31, Crohn's disease, FAMIN, LACC1, Still's disease, immunometabolism, pH homeostasis, purine metabolism, purine nucleotide cycle, redox homeostasis},
  author = {Cader ZM and Rodrigues R and West J and Sewell G and Md-Ibrahim M and Reikine S and Sirago G and Unger L and Inglesias-Romero A and Ramshorn K and Haag L and Saveljeva S and Ebel J and Rosenstiel P and Kaneider N and Lee J and Lawley T and Bradley A and Dougan G and Modis Y and Griffin J and Kaser A},
  title = {FAMIN Is a Multifunctional Purine Enzyme Enabling the Purine Nucleotide Cycle.},
  abstract = {<p>Mutations in FAMIN cause arthritis and inflammatory bowel disease in early childhood, and a common genetic variant increases the risk for Crohn's disease and leprosy. We developed an unbiased liquid chromatography-mass spectrometry screen for enzymatic activity of this orphan protein. We report that FAMIN phosphorolytically cleaves adenosine into adenine and ribose-1-phosphate. Such activity was considered absent from eukaryotic metabolism. FAMIN and its prokaryotic orthologs additionally have adenosine deaminase, purine nucleoside phosphorylase, and S-methyl-5'-thioadenosine phosphorylase activity, hence, combine activities of the namesake enzymes of central purine metabolism. FAMIN enables in macrophages a purine nucleotide cycle (PNC) between adenosine and inosine monophosphate and adenylosuccinate, which consumes aspartate and releases fumarate in a manner involving fatty acid oxidation and ATP-citrate lyase activity. This macrophage PNC synchronizes mitochondrial activity with glycolysis by balancing electron transfer to mitochondria, thereby supporting glycolytic activity and promoting oxidative phosphorylation and mitochondrial H and phosphate recycling.</p>},
  year = {2020},
  journal = {Cell},
  volume = {180},
  pages = {278-295.e23},
  month = {01/2020},
  issn = {1097-4172},
  url = {10.1016/j.cell.2019.12.017},
  doi = {10.1016/j.cell.2019.12.017},
  language = {eng},
}