Tetrahydrofolate carries one-carbon fragments at specific nitrogen positions for biosynthetic reactions.
Attachment sites and pharmaceutical forms
•
N-5 can carry formyl, formimino, or methyl groups; N-10 can carry a formyl group. Methylene and methenyl groups bridge N-5 and N-10.
•
5-Formyltetrahydrofolate, known as folinic acid, is more stable than folate and is used pharmaceutically. The synthetic racemic compound is leucovorin.
Entry and interconversion of one-carbon fragments
•
Methylenetetrahydrofolate is the major entry point for one-carbon fragments into substituted folates and is formed through reactions of glycine, serine, and choline with tetrahydrofolate.
•
Serine is the most important source of substituted folates for biosynthesis. Serine hydroxymethyltransferase activity is regulated by folate substitution and folate availability.
•
The serine hydroxymethyltransferase reaction is reversible. In the liver, it can produce serine from glycine for gluconeogenesis.
•
Methylene-, methenyl-, and 10-formyltetrahydrofolates are interconvertible.
Maintaining free folate
•
When one-carbon folates are unnecessary, formyltetrahydrofolate is oxidized to release carbon dioxide, maintaining a pool of free folate.