Question

Most one-carbon transfers are promoted by one of three cofactors: biotin, tetrahydrofolate, or S-adenosylmethionine. S-Adenosylmethionine is generally used as a methyl group donor; the transfer potential of the methyl group in N5-methyltetrahydrofolate is insufficient for most biosynthetic reactions. However, one example of the use of N5-methyltetrahydrofolate in methyl group transfer is in methionine formation by the methionine synthase reaction; methionine is the immediate precursor of S-adenosylmethionine. List these three methyl donors in order of methyl group transfer potential highest to lowest.

N5-methyltetrahydrofolate, methionine, S-adenosylmethionine.

Explain how the methyl group of S-adenosylmethionine can be derived from N5-methyltetrahydrofolate, even though the transfer potential of the methyl group in N5-methyltetrahydrofolate is one one-thousandth of that in S-adenosylmethionine.

The group transfer potential of the methyl group in methionine is naturally higher than in N5-methyltetrahydrofolate because the methyl group is attached to a sulfur atom.

The group transfer potential of the methyl group in methionine is increased by the reaction with ATP to form S-adenosylmethionine, which involves hydrolysis of three phosphate anhydride bonds.

The group transfer potential of the methyl group in N5-methyltetrahydrofolate is increased by conversion of tetrahydrofolate to dihydrofolate during transfer.

The group transfer potential of the methyl group in N5-methyltetrahydrofolate is increased by oxidation to N5, N10-methylenetetrahydrofolate prior to transfer.

Answer 1