| First Author | Cader MZ | Year | 2020 |
| Journal | Cell | Volume | 180 |
| Issue | 2 | Pages | 278-295.e23 |
| PubMed ID | 31978345 | Mgi Jnum | J:289094 |
| Mgi Id | MGI:6436442 | Doi | 10.1016/j.cell.2019.12.017 |
| Citation | Cader MZ, et al. (2020) FAMIN Is a Multifunctional Purine Enzyme Enabling the Purine Nucleotide Cycle. Cell 180(2):278-295.e23 |
| abstractText | 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. |
