Folate Coenzymes Are Used in Reactions for One-Carbon Transfers

Folate Coenzymes Are Used in Reactions for One-Carbon Transfers 

The tetrahydrofolates do not function as tightly enzyme-bound coenzymes. Rather, they function as cosubstrates for a variety of enzymes associated with one-carbon metabolism. /Vl0-formyltetrahydrofolate is produced enzymatically from tetrahydrofolate and formate in an ATP-linked process in which formate is activated by phosphorylation to formyl phosphate the formyl group of formyl phosphate is then transferred to A10 of tetrahydrofolate. A10-Formyltetrahydrofolate is a formyl donor substrate for some enzymes and is interconvertible with A5,A10-methenyltetrahydrofolate by the action of cyclohydrolase. 

A1 °-Methylcnctctrahydrofolate is a hydroxymethyl-group donor substrate for several enzymes and a methyl-group donor substrate for thymidylate synthase (fig. 10.15). It arises in living cells from the reduction of A5,A10-methenyltetrahydrofolate by NADPH and also by the serine hydroxymethyltransferase-catalyzed reaction of serine with tetrahydrofolate. 

A5-Methyltetrahydrofolate is the methyl-group donor substrate for methionine synthase, which catalyzes the transfer of the five-methyl group to the sulfhydryl group of homocysteine. This and selected reactions of the other folate derivatives are outlined in figure 10.15, which emphasizes the important role tetrahydrofolate plays in nucleic acid biosynthesis by serving as the immediate source of one-carbon units in purine and pyrimidine biosynthesis. 

Formaldehyde is a toxic substance that reacts spontaneously with amino groups of proteins and nucleic acids, hydroxymethylating them and forming methylene-bridge crosslinks between them. Free formaldehyde therefore wreaks havoc in living cells and could not serve as a useful hydroxymethylating agent. In the form of A5,A10-methylenetetrahydrofolate, however, its chemical reactivity is attenuated but retained in a potentially available form where needed for specific enzymatic action. Formate, how- 

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Reactions Requiring Acyl-Group Transfers Linked to Oxidation—Reduction Biotin Mediates Carboxylations Folate Coenzymes Are Used in Reactions for One-Carbon Transfers... 

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