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Inhibition of HKSV28 cell growth by 5,11-methenyl-tetrahydrohomofolate.
- Source :
-
Molecular pharmacology [Mol Pharmacol] 1984 Mar; Vol. 25 (2), pp. 294-302. - Publication Year :
- 1984
-
Abstract
- 5,11-Methenyl-tetrahydrohomofolate (5,11-methenyl-H4homofolate), a reduced folate analogue, inhibited hamster kidney HKSV28 cells grown in vitro. Hypoxanthine protected the cells from growth inhibition but thymidine had no effect, suggesting that the blockage was in the purine biosynthetic pathway. The measurement of formylglycinamide ribonucleotide levels in the presence of the drug showed that a decrease in these levels was a significant and primary effect of the compound, but the effect had an onset time of approximately 4 hr. In contrast, incubation of the cells with the hydrolysis products 11-formyl-H4/H2homofolate resulted in an immediate decrease in formylglycinamide synthesis. The latter formyl derivatives were shown to be potent competitive inhibitors of glycinamide ribonucleotide transformylase (EC 2.1.2.2) from chicken liver. However, the cell inhibition by 5,11-methenyl-H4homofolate was not confined to glycinamide ribonucleotide transformylase, since the cells were not protected by the presence of aminoimidazole carboxamide. Although aminoimidazole carboxamide ribonucleotide transformylase (EC 2.1.2.3) from chicken liver was not inhibited by these derivatives, we propose that intracellular glutamate elongation of the 11-formyl-H4/H2homofolates might lead to inhibition of both transformylase enzymes.
- Subjects :
- Animals
Cells, Cultured
Cricetinae
Folic Acid metabolism
Glycine metabolism
Hydrolysis
Methotrexate pharmacology
Phosphoribosylglycinamide Formyltransferase
Ribonucleotides metabolism
Acyltransferases antagonists & inhibitors
Cell Division drug effects
Folic Acid analogs & derivatives
Folic Acid pharmacology
Hydroxymethyl and Formyl Transferases
Subjects
Details
- Language :
- English
- ISSN :
- 0026-895X
- Volume :
- 25
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 6700575