Adam G Maynard, Nancy K Pohl, Annabel P Mueller, Boryana Petrova, Alan Y L Wong, Peng Wang, Andrew J Culhane, Jeannette R Brook, Leah M Hirsch, Ngoc Hoang, Orville Kirkland, Tatum Braun, Sarah Ducamp, Mark D Fleming, Hojun Li, Naama Kanarek
Folate, an essential vitamin, is a one-carbon acceptor and donor in key metabolic reactions. Erythroid cells harbor a unique sensitivity to folate deprivation, as revealed by the primary pathological manifestation of nutritional folate deprivation: megaloblastic anemia. To study this metabolic sensitivity, we applied mild folate depletion to human and mouse erythroid cell lines and primary murine erythroid progenitors. We show that folate depletion induces early blockade of purine synthesis and accumulation of the purine synthesis intermediate and signaling molecule, 5'-phosphoribosyl-5-aminoimidazole-4-carboxamide (AICAR), followed by enhanced heme metabolism, hemoglobin synthesis, and erythroid differentiation...
February 2, 2024: Science Advances