Shane, B.B.ShaneChoi, Y.-J.Y.-J.ChoiLin, B.-F.B.-F.LinHuang, R.-F.R.-F.HuangHsu, J.-C.J.-C.HsuBI-FONG LIN2018-09-102018-09-10199608926638http://www.scopus.com/inward/record.url?eid=2-s2.0-33749157568&partnerID=MN8TOARShttp://scholars.lib.ntu.edu.tw/handle/123456789/325973https://www.scopus.com/inward/record.uri?eid=2-s2.0-33749157568&partnerID=40&md5=518b7c494349789248f24195378ea92aWe are studying the mechanisms by which folylpolyglutamate formation in mammalian tissues controls one carbon metabolism and regulates intracellular folate levels. Genetic approaches have been used to develop model mammalian cells defective in cytosolic and/or mitochondrial folate metabolism to explore the role of the mitochondria in folate and one carbon metabolism. Folylpolyglutamate distributions are different in mitochondria and cytosol and mitochondrial folylpolyglutamate synthetase (FPGS) activity is required for folate accumulation by the mitochondrion. FPGS is located in the mitochondria and cytosol of eukaryotic cells and mitochondrial FPGS activity is required for mitochondrial one carbon metabolism including glycine synthesis and for a normal one carbon flux in the cytosol. Mitochondrial serine hydroxymethyltransferase (SHMT) is also required for normal rates of cellular glycine synthesis and overexpression of cytosolic SHMT will not meet the cells need for glycine. Defective mitochondrial folate metabolism causes defects in cytosolic purine synthesis. Cytosolic folate one carbon pools and methionine synthesis are also impaired. Our studies have also shown that pteroyltriglutamates function effectively in the metabolic cycles of purine, glycine and thymidylate synthesis but that the longer glutamate chain length folates typically found in mammalian cells are required for methionine synthesis.journal article2-s2.0-33749157568