Folate is reduced to dihydrofolate (DHF) Extracellular 5-methyltetrahydrofolate import across the plasma membrane Cytosolic folate export across the plasma membrane Extracellular folate import across the plasma membrane Mitochondrial tetrahydrofolate export across the inner mitochondrial membrane Conversion of mitochondrial THF to THF-polyglutamate Conversion of cytosolic 5-methyltetrahydrofolate (5-methylTHF) to 5-methylTHF-polyglutamate Cytosolic tetrahydrofolate import across the inner mitochondrial membrane DHF is reduced to tetrahydrofolate (THF) Conversion of cytosolic THF to THF-polyglutamate THF polyglutamate + formate + ATP => 10-formylTHF polyglutamate + ADP + orthophosphate 5,10-methenylTHF polyglutamate + NADPH + H+ <=> 5,10-methyleneTHF polyglutamate + NADP+ 10-formylTHF polyglutamate <=> 5,10-methenylTHF polyglutamate + H2O 5,10-methyleneTHF polyglutamate + NADPH + H+ => 5-methylTHF polyglutamate + NADP+ Tetrahydrofolate polyglutamate (THF polyglutamate) + serine <=> 5,10-methyleneTHF polyglutamate + glycine 5,10-methyleneTHF polyglutamate + glycine <=> tetrahydrofolate polyglutamate (THF polyglutamate) + serine 5,10-methyleneTHF polyglutamate + NADP+ <=> 5,10-methenylTHF polyglutamate + NADPH + H+ 5,10-methenylTHF polyglutamate + H2O <=> 10-formylTHF polyglutamate PathwayStep2389 PathwayStep2388 PathwayStep2390 PathwayStep2393 PathwayStep2391 PathwayStep2392 PathwayStep2376 PathwayStep2378 PathwayStep2377 PathwayStep2379 PathwayStep2380 PathwayStep2381 PathwayStep2382 PathwayStep2383 PathwayStep2384 PathwayStep2385 PathwayStep2386 PathwayStep2387 Metabolism of folate and pterines Folates are essential cofactors that provide one-carbon moieties in various states of reduction for biosynthetic reactions. Processes annotated here include transport reactions by which folates are taken up by cells and moved intracellularly, folate conjugation with glutamate (required for folate retention within a cell), and some of the key reactions in the generation of reduced folates and one-carbon derivatives of folate. GENE ONTOLOGYGO:0046655 Pubmed10466189 Pubmed11001804 Reactome Database ID Release 43196757 Reactome, http://www.reactome.org ReactomeREACT_11167