Polyglutamyl derivatives of tetrahydrofolate as substrates for Lactobacillus casei thymidylate synthase

Roy L. Kisliuk, Yvette Gaumont, Eileen M Lafer, Charles M. Baugh, John A. Montgomery

Research output: Contribution to journalArticle

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Abstract

Tetrahydropteroylpolyglutamates containing up to seven Glu residues were tested as substrates for Lactobacillus casei thymidylate synthase. The Km values decreased from 24 μM for the monoglutamate to 1.8 μM for the triglutamate. Addition of residues 4, 5, 6, and 7 did not decrease the Km further. When monoglutamate and polyglutamate substrates were simultaneously incubated with the enzyme, the rate observed was characteristic of the polyglutamate even when the monoglutamate concentration was 44 times that of the polyglutamate. Iodoacetamide treatment inhibited the enzyme to the same extent with monoglutamate and polyglutamate substrates. Addition of 0.3 M NaCl doubled the rate obtained with the polyglutamate substrate whereas the rate with the monoglutamate was inhibited 25%. MgCl2 stimulated the reaction only 10% with the polyglutamate substrate compared with 80% stimulation obtained with the monoglutamate. Inhibition by fluorodeoxyuridylate was similar with both mono- and polyglutamate substrates; however, with the phosphonate derivative of fluorodeoxyuridine, the polyglutamate substrate enhanced inhibition 5- to 8-fold.

Original languageEnglish (US)
Pages (from-to)929-934
Number of pages6
JournalBiochemistry
Volume20
Issue number4
StatePublished - 1981
Externally publishedYes

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Polyglutamic Acid
Lactobacillus casei
Thymidylate Synthase
Derivatives
Substrates
Fluorodeoxyuridylate
Floxuridine
Iodoacetamide
Organophosphonates
Magnesium Chloride
5,6,7,8-tetrahydrofolic acid
Enzymes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Kisliuk, R. L., Gaumont, Y., Lafer, E. M., Baugh, C. M., & Montgomery, J. A. (1981). Polyglutamyl derivatives of tetrahydrofolate as substrates for Lactobacillus casei thymidylate synthase. Biochemistry, 20(4), 929-934.

Polyglutamyl derivatives of tetrahydrofolate as substrates for Lactobacillus casei thymidylate synthase. / Kisliuk, Roy L.; Gaumont, Yvette; Lafer, Eileen M; Baugh, Charles M.; Montgomery, John A.

In: Biochemistry, Vol. 20, No. 4, 1981, p. 929-934.

Research output: Contribution to journalArticle

Kisliuk, RL, Gaumont, Y, Lafer, EM, Baugh, CM & Montgomery, JA 1981, 'Polyglutamyl derivatives of tetrahydrofolate as substrates for Lactobacillus casei thymidylate synthase', Biochemistry, vol. 20, no. 4, pp. 929-934.
Kisliuk, Roy L. ; Gaumont, Yvette ; Lafer, Eileen M ; Baugh, Charles M. ; Montgomery, John A. / Polyglutamyl derivatives of tetrahydrofolate as substrates for Lactobacillus casei thymidylate synthase. In: Biochemistry. 1981 ; Vol. 20, No. 4. pp. 929-934.
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AU - Montgomery, John A.

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