A METHYLATED DERIVATIVE OF TETRAHYDROFOLATE AS AN INTERMEDIATE OF METHIONINE BIOSYNTHESIS¹

Studies on the Identification of a Folate Compound of Human Serum*

“…The concentrated serum extract was tested for microbiological activity; 5 piI of the concentrate contained 78 mpug of "folate activity" for L. casei and 4.7 mjug for S. faecalis. In Table IV (6). The experiments of these several laboratories thus provide convincing evidence that N5-methyl tetrahydrofolate is a major constituent of at least two tissues, namely liver and serum, and has an important metabolic function in the synthesis of methyl-containing compounds such as methionine and, indirectly, choline (21 …”

“…It did not replace folic acid and N'-formyl tetrahydrofolate as a growth factor for S. faecalis and L. citrovorum, respectively (6). Since on hydrolysis with 6 N HCl at 1100C this compound yielded 1 mole glutamate per mole of N-methyl group, it is a monoglutamate.…”

“…N'-methyl tetrahydrofolate is an intermediate of methionine biosynthesis isolated by Larrabee and Buchanan (5,6) and was prepared by their procedure (6). It did not replace folic acid and N'-formyl tetrahydrofolate as a growth factor for S. faecalis and L. citrovorum, respectively (6).…”

“…On the basis of this similarity, serum folate compounds were considered to be pteroylpolyglutamates. Larrabee, Buchanan, Rosenthal and Cathou (5,6) recently have isolated a monoglutamate (N5-methyl tetrahydrofolate) as an intermediate of methionine biosynthesis, and Keresztesy and Donaldson (7,8) have isolated a compound with similar properties (prefolic A) from horse liver. Both compounds exhibit the same response in growth to the three organisms as that shown by the serum folate derivative.…”

Interrelations of Vitamin B12 and Folic Acid Metabolism: Folic Acid Clearance Studies*

“…Recent studies (23) suggest that most of the L. casei activity in human serum is due to a material similar or identical to N5-methyl-tetrahydrofolic acid (N5-methyl THFA), the folic acid coenzyme active as an intermediate in methionine biosynthesis (24)(25)(26)(27)(28)(29), which requires vitamin B12 in order to act (25,26,30,31). Table VII summarizes present knowledge concerning the folic acid activity for microorganisms of various folic acid analogues.…”