NADPH production by the oxidative pentose-phosphate pathway supports folate metabolism.

ABSTRACT: NADPH donates high energy electrons for antioxidant defense and reductive biosynthesis. Cytosolic NADP is recycled to NADPH by the oxidative pentose phosphate pathway (oxPPP), malic enzyme 1 (ME1) and isocitrate dehydrogenase 1 (IDH1). Here we show that any one of these routes can support cell growth, but the oxPPP is uniquely required to maintain a normal NADPH/NADP ratio, mammalian dihydrofolate reductase (DHFR) activity and folate metabolism. These findings are based on CRISPR deletions of glucose-6-phosphate dehydrogenase (G6PD, the committed oxPPP enzyme), ME1, IDH1, and combinations thereof in HCT116 colon cancer cells. Loss of G6PD results in high NADP, which induces compensatory increases in ME1 and IDH1 flux. But the high NADP inhibits dihydrofolate reductase (DHFR), resulting in

SUBMITTER: Chen L 

PROVIDER: S-EPMC6489125 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature