Hydroxymethyltransferases

Hydroxymethyltransferases are a class of enzymes that catalyze the transfer of a hydroxymethyl group (-CH2OH) from one molecule to another. This group is often derived from formaldehyde or a similar one-carbon unit. These enzymes play crucial roles in various metabolic pathways, particularly in amino acid metabolism and nucleotide biosynthesis.

A key example is serine hydroxymethyltransferase (SHMT). SHMT is essential for one-carbon metabolism, interconverting serine and glycine. In this reaction, SHMT uses tetrahydrofolate (THF) as a cofactor to transfer the hydroxymethyl group from serine to THF, producing glycine and 5,10-methylenetetrahydrofolate. This 5,10-methylenetetrahydrofolate is a vital donor of one-carbon units for numerous biosynthetic processes, including purine and thymidylate synthesis.

Another important hydroxymethyltransferase is thymidylate synthase, which is involved in DNA synthesis. This enzyme catalyzes the reductive methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) using 5,10-methylenetetrahydrofolate as the methyl donor. The hydroxymethyl group from the folate cofactor is ultimately incorporated into the dTMP molecule.

The activity of hydroxymethyltransferases is critical for cellular growth and division. Dysregulation of these enzymes can lead to various diseases, including certain types of cancer and developmental disorders, making them targets for therapeutic intervention. Research continues to explore the diverse functions and mechanisms of these versatile enzymes across different organisms.