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Polyglutamate derivatives of folic acid coenzymes and methotrexate

Authors
Journal
Life Sciences
0024-3205
Publisher
Elsevier
Publication Date
Volume
26
Issue
9
Identifiers
DOI: 10.1016/0024-3205(80)90256-8
Disciplines
  • Biology
  • Medicine

Abstract

Abstract Polyglutamate derivatives of the folate coenzymes are widely distributed in nature. Frequently, they are the predominant form of intracellular folate, and recent investigations have indicated that polyglutamates are the preferred substrates for most of the enzymes of folate metabolism. Dietary folates are mostly polyglutamate conjugates which must be broken down to the mono- or diglutamates before intestinal absorption can occur. Intracellularly, pteroyl monoglutamates are converted to the polyglutamate form, a process which appears to favor their cellular retention. Alterations in polyglutamate chain length may play an important role in the regulation of folate metabolism. Polyglutamate derivatives of the folate antagonist methotrexate have also been isolated. The synthesis and biological properties of these compounds along with their potential chemotherapeutic role are discussed.

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