Characterization of the function of mammalian folylpolyglutamate synthetase (FPGS).

Abstract:

:The function and characteristics of mouse folylpolyglutamate synthetase have been examined. Folate polyglutamates were poor substrates for the efflux mechanism for monoglutamates in L1210 mouse leukemia cells, with negligible loss of preformed folate polyglutamates to the medium over four hours. Disruption of folate metabolism with methotrexate did not augment efflux of folate polyglutamates. Folylpolyglutamate synthetase, partially purified from mouse liver, was found to accept a variety of folate derivatives as substrates, including pteroic acid and methotrexate; however, the concentration of these substrates that saturated the reaction varied considerably. The enzyme that catalyzed the addition of glutamic acid to methotrexate and to the naturally-occurring folate monoglutamates appeared to be the same. The cytotoxicity of folylpolyglutamate synthetase inhibitors was predicted to require continued cell division since their effects would be based upon a decreased rate of synthesis of folate cofactors capable of retention by the cell membrane. Hence folylpolyglutamate synthetase inhibitors should have low toxicity to nonproliferative cell populations.

journal_name

Adv Exp Med Biol

authors

Moran RG

doi

10.1007/978-1-4757-5241-0_24

subject

Has Abstract

pub_date

1983-01-01 00:00:00

pages

327-39

eissn

0065-2598

issn

2214-8019

journal_volume

163

pub_type

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