02408nas a2200517   4500000000100000008004100001260001200042653001300054653002000067653001000087653001000097653002000107653002100127653001900148653002200167653002800189653002200217100001300239700001600252700001100268700001300279700001700292700001400309700001300323700001200336700002300348700001500371700001100386700001600397700001100413700001700424700001500441700001000456700001300466700001400479700001300493700001200506700001400518700001200532245008300544856003100627300001600658490000800674520119400682022001401876       2020                            d  c01/202010aC13orf3110aCrohn's disease10aFAMIN10aLACC110aStill's disease10aimmunometabolism10apH homeostasis10apurine metabolism10apurine nucleotide cycle10aredox homeostasis1 aCader ZM1 aRodrigues R1 aWest J1 aSewell G1 aMd-Ibrahim M1 aReikine S1 aSirago G1 aUnger L1 aInglesias-Romero A1 aRamshorn K1 aHaag L1 aSaveljeva S1 aEbel J1 aRosenstiel P1 aKaneider N1 aLee J1 aLawley T1 aBradley A1 aDougan G1 aModis Y1 aGriffin J1 aKaser A00aFAMIN Is a Multifunctional Purine Enzyme Enabling the Purine Nucleotide Cycle.  u10.1016/j.cell.2019.12.017  a278-295.e230 v1803 a<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>  a1097-4172