Tetrahydrofolic acid derivatives, scheme

A metabolic pathway that has received considerable attention is the conversion of 2 -deoxyuridine 5 -monophosphate (dUMP, 6.60) to thymidine 5 -monophosphate (TMP, 6.61) (Scheme 6.13). Without an adequate supply of TMP, a cell or bacterium cannot create DNA for cell division. Therefore, blocking TMP synthesis is an attractive method for slowing the advancement of certain cancers and bacterial infections. Important molecules in the methylation of dUMP are the various folic acid derivatives folic acid (FA, 6.62), dihydrofolic acid (DHF, 6.63), tetrahydrofolic acid (THF, 6.64), and N5, A1 "-methylene tetrahydrofolic acid (MTHF, 6.65) (Figure 6.23). These structures... 

The stereochemistry of many of the biological reactions involving serine and its derivatives has been studied using the labeled compounds prepared above. The carbon atom, C-3, of serine acts as a source of the one carbon unit transferred by the coenzyme tetrahydrofolic acid 87 (95) (Scheme 24). It is initially transferred to the coenzyme 87 to give 5,10-methylenetetrahydro-folic acid 56a and glycine 23 in a reaction catalyzed by the enzyme serine... 

Methylation of homocysteine to methionine can be accomplished by one of several sequences. A major route is from a N -methyl-tetrahydrofolic acid (CHg—FH4) derivative. In some organisms a coenzyme derivative of vitamin B12 is also required, where it functions in its reduced form (B12, in the following scheme) as an intermediate methyl carrier ... 

Scheme III shows the experimental arrangement to study the second one-carbon transfer reaction we investigated, the formation of thymidylic acid from uridylic acid catalyzed by thymidy-late synthetase. In this reaction, the methyl group of thymidy-late is derived from the carbon and the two hydrogens of the methylene bridge plus H-6 of methylene-tetrahydrofolate. To study the stereochemistry of this reaction, we (5) synthesized serine stereospecifically labeled with tritium and deuterium at...

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