Folylpoly-gamma-glutamate synthetases: properties and regulation.

Abstract

The substrate specificities of folylpolyglutamate synthetases from Corynebacterium species, Lactobacillus casei, Streptococcus faecalis, and Chinese hamster ovary (CHO) cells are described. The purified Corynebacterium enzyme catalyzes the addition of glutamate moieties to reduced pteroylmonoglutamates, and to 5,10-methylenetetrahydropteroyldi- and triglutamates. The purified protein also possesses a separate dihydrofolate synthetase activity. Binding of pteroate substrates to dihydrofolate synthetase impairs folate binding to folylpolyglutamate synthetase. The in vivo distribution of folylpolyglutamates in bacteria and mammalian cells, which differs from source to source, appears to be a reflection of the ability of folylpolyglutamates to act as substrates for folylpolyglutamate synthetases from different sources. Bacterial synthetases use a variety of pteroylmonoglutamates as their preferred monoglutamate substrate, but use 5,10-methylenetetrahydropteroyl polyglutamates as their preferred, and sometimes only, polyglutamate substrates. Mono- and polyglutamyl forms of tetrahydrofolate are the preferred substrates of the CHO cell synthetase. Products of one carbon metabolism do not affect the in vivo distribution of folylpolyglutamates in CHO cells. Although adenine changes the distribution of folylpolyglutamates in bacteria, this effect is mediated by changing the substrate availability for the synthetase reaction, and not by regulating the levels of the synthetase per se.