RT Journal Article
SR Electronic
T1 Inhibition of Serine Metabolism by Tetrahydrohomofolate in L1210 Mouse Leukemia Cells
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 481
OP 490
VO 19
IS 3
A1 KEVIN J. SCANLON
A1 ARLENE R. CASHMORE
A1 BARBARA A. MOROSON
A1 ROBERT N. DREYER
A1 JOSEPH R. BERTINO
YR 1981
UL http://molpharm.aspetjournals.org/content/19/3/481.abstract
AB Tetrahydrohomofolate, a reduced folate analogue, inhibited mouse leukemia L1210 grown in vitro. However, it was found to be a substrate for the following enzymes: methylene tetrahydrofolate reductase (EC 1.1.1.68), methylene tetrahydrofolate dehydrogenase (EC 1.5.1.5), 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), and thymidylate synthetase (EC 2.1.1.45). Serine transhydroxymethylase (EC 2.1.2.1) was markedly inhibited by the analogue (I50 = 62.5 µM). In whole cell studies, incorporation of [3-14C]serine into both nucleic acids and methionine was significantly inhibited by tetrahydrohomofolate. The uptake of [3H]methionine was also inhibited at concentrations of tetrahydrofolate of 50 µM or higher. The inhibition of serine transhydroxymethylase together with the inhibition of methionine uptake may explain, at least in part, the ability of tetrahydrohomofolate to inhibit growth of L1210 cells. ACKNOWLEDGMENT The authors gratefully acknowledge the help and advice of Dr. Bruce Dolnick of this laboratory with the enzyme kinetic studies.