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Folylpoly-γ-glutamate synthesis by bacteria and mammalian cells

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Summary

The purification and properties of folylpolyglutamate synthetase fromCorynebacterium sp, and some properties of partially purified enzyme fromLactobacillus casei, Streptococcus faecalis, Neurospora crassa, pig liver, and Chinese hamster ovary cells, are described.

TheCorynebacterium enzyme catalyzes a MgATP-dependent addition of glutamate to a variety of reduced pteroate and pteroylmono-, di-, and triglutamate substrates, with the concomitant production of MgADP and phosphate. Although glutamate moieties are added in a sequential fashion, the kinetic mechanism, which is Ordered Ter Ter, precludes the sequential addition of glutamate moieties to enzyme-bound folate. It is suggested that catalysis precedes via the formation of a pteroyl-γ-glutamyl phosphate intermediate.

Thein vivo distribution of folylpolyglutamates in bacteria and mammalian cells, which differ from source to source, appear to be a reflection of the ability of folylpolyglutamates to act as substrates for folylpolyglutamate synthetases from different sources.

Only one enzyme appears to be involved in the conversion of pteroylmonoglutamates to polyglutamate forms in both bacteria and mammalian cells. Bacterial folylpolyglutamate synthetases use a variety of pteroylmonoglutamates as their preferred monoglutamate substrate, but use 5,10-methylenetetrahydropteroylpolyglutamates as their preferred, and sometimes only, polyglutamate substrate. Mono- and polyglutamyl forms of tetrahydrofolate are the preferred substrates of mammalian folylpolyglutamate synthetases.

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Abbreviations

PteGlu:

pteroylmonoglutamic acid, folic acid

H4PteGlun :

5,6,7,8-tetrahydropteroylpoly-γ-glutamate

pABAglun :

p-aminobenzoylpoly-γ-glutamate

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Authors and Affiliations

  1. Dept. of Biochemistry, School of Hygiene and Public Health, The Johns Hopkins University, 615 North Wolfe Street, 21205, Baltimore, MD, USA

    David J. Cichowicz, Siang K. Foo & Barry Shane

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  1. David J. Cichowicz
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  2. Siang K. Foo
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  3. Barry Shane
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Cichowicz, D.J., Foo, S.K. & Shane, B. Folylpoly-γ-glutamate synthesis by bacteria and mammalian cells. Mol Cell Biochem 39, 209–228 (1981). https://doi.org/10.1007/BF00232575

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  • DOI: https://doi.org/10.1007/BF00232575

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