6t1b

Publication Abstract from PubMed

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.

FAMIN Is a Multifunctional Purine Enzyme Enabling the Purine Nucleotide Cycle.,Cader MZ, de Almeida Rodrigues RP, West JA, Sewell GW, Md-Ibrahim MN, Reikine S, Sirago G, Unger LW, Iglesias-Romero AB, Ramshorn K, Haag LM, Saveljeva S, Ebel JF, Rosenstiel P, Kaneider NC, Lee JC, Lawley TD, Bradley A, Dougan G, Modis Y, Griffin JL, Kaser A Cell. 2020 Jan 23;180(2):278-295.e23. doi: 10.1016/j.cell.2019.12.017. PMID:31978345^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.