Exploring the effects of antifolates on one-carbon metabolism in tumor cells: Experimental and SPICE2 network thermodynamic analyses

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Recent advances in the understanding of (anti)folate biochemistry and pharmacology made possible by the application of network thermodynamic modeling are discussed. The data indicate, and simulations predict, that low levels of residual dihydrofolate reductase catalytic activity can have an important effect on the steady-state dihydrofolate level achieved by inhibitors of this enzyme. With low residual levels of dihydrofolate reductase catalytic activity, modest inhibition of thymidylate synthase can influence the extent of interconversion of tetrahydrofolate cofactors to dihydrofolate. The studies indicate that the observed partial interconversion of tetrahydrofolate cofactors to dihydrofolate can be accounted for on the basis of compartmentation of a portion of cellular folates which makes them unavailable for oxidation through thymidylate synthase.

Original languageEnglish (US)
Title of host publicationConference Proceedings - IEEE SOUTHEASTCON
PublisherPubl by IEEE
Pages153-157
Number of pages5
ISBN (Print)0780300335
Publication statusPublished - Jan 1 1991
Externally publishedYes
EventIEEE Proceedings of the SOUTHEASTCON '91 - Williamsburg, VA, USA
Duration: Apr 8 1991Apr 10 1991

Publication series

NameConference Proceedings - IEEE SOUTHEASTCON
Volume1
ISSN (Print)0734-7502

Other

OtherIEEE Proceedings of the SOUTHEASTCON '91
CityWilliamsburg, VA, USA
Period4/8/914/10/91

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ASJC Scopus subject areas

  • Electrical and Electronic Engineering

Cite this

Seither, R. L., & Goldman, I. D. (1991). Exploring the effects of antifolates on one-carbon metabolism in tumor cells: Experimental and SPICE2 network thermodynamic analyses. In Conference Proceedings - IEEE SOUTHEASTCON (pp. 153-157). (Conference Proceedings - IEEE SOUTHEASTCON; Vol. 1). Publ by IEEE.