Thymidylate synthase, dihydrofolate reductase, folyl binder, 10-formyl-H4PteGlu synthetase, 5,10-methenyl-H4PteGlu cyclohydrolase and 5,10-methylene-H4PteGlu dehydrogenase derived from cells of human origin.
In the past few years we have been engaged in studying several folate cofactor requiring enzymes derived from human cells; namely thymidylate synthase, dihydrofolate reductase, folyl binder, 10-formyl-H4PteGlu synthetase, 5,10-methenyl-H4PteGlu cyclohydrolase and 5,10-methylene-H4PteGlu dehydrogenase. These have been purified and several properties have been examined, in particular the interactions with folyl-polyglutamate forms as substrates and inhibitors. Folylpolyglutamates are better substrates for thymidylate synthase, 10-formyl-H4PteGlu synthetase, and 5,10-methylene-H4PteGlu dehydrogenase when NADP is lower than 30 microM, whereas dihydrofolate reductase and membrane associated folyl binder do not distinguish between folylmono- and polyglutamates. Analog studies with thymidylate synthase suggest that there are two types of folate binding sites and this led us to propose a model for the subunit association.
D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2); D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D002277:Carcinoma / Q000201:enzymology; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000378:metabolism*; D005574:Formate-Tetrahydrofolate Ligase / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D007945:Leukemia, Lymphoid / Q000201:enzymology; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology; D008025:Ligases / Q000378:metabolism*; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008780:Methyltransferases / Q000378:metabolism*; D051379:Mice; D009062:Mouth Neoplasms / Q000201:enzymology; D011956:Receptors, Cell Surface; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism*; D013940:Thymidylate Synthase / Q000378:metabolism*
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D005492:Folic Acid; D000429:Alcohol Oxidoreductases; D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2); D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013762:Tetrahydrofolate Dehydrogenase; D008780:Methyltransferases; D013940:Thymidylate Synthase; D008025:Ligases; D005574:Formate-Tetrahydrofolate Ligase