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

  • Yung-chi Cheng
  • Barbara A. Domin
  • Dennis Conrad
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 163)


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 μM, 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.


Acute Myelocytic Leukemia Chronic Lymphocytic Leukemia Dihydrofolate Reductase Ammonium Sulfate Fractionation Folate Cofactor 
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Copyright information

© Springer Science+Business Media New York 1983

Authors and Affiliations

  • Yung-chi Cheng
    • 1
  • Barbara A. Domin
    • 1
  • Dennis Conrad
    • 1
  1. 1.Department of Pharmacology and Medicine, Cancer Drug Development Program, School of MedicineUniversity of North Carolina at Chapel HillChapel HillUSA

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