Folic Acid and Amino Acid Metabolism

Some synthetic pathways require the addition of single-carbon groups that exist in a variety of oxidation states, including formyl, methenyl, methylene, and methyl. These single-carbon groups can be transferred from carrier compounds such as THF and SAM to specific structures that are being synthesized or modified. The “one-carbon pool” refers to the single-carbon units attached to this group of carriers. [Note: CO2, coming from bicarbonate (HCO3–), is carried by the vitamin biotin , which is a prosthetic group for most carboxylation reactions but is not considered a member of the one-carbon pool.
Defects in the ability to add or remove biotin from carboxylases result in multiple carboxylase deficiency. Treatment is supplementation with biotin.]
A. Folic acid and one-carbon metabolism
The active form of folic acid, THF, is produced from folate by dihydrofolate reductase in a two-step reaction requiring two nicotinamide adenine dinucleotide phosphate (NADPH). The one-carbon unit carried by THF is bound to N⁵ or N¹⁰ or to both N⁵ and N¹⁰. Figure 1 shows the structures of the various members of the THF family and their interconversions and indicates the sources of the one-carbon units and the synthetic reactions in which the specific members participate. [Note: Folate deficiency presents as a megaloblastic anemia because of decreased availability of the purines and of the thymidine monophosphate needed for DNA synthesis .]

Figure 1: Summary of the interconversions and uses of THF. [Note: N⁵,N¹⁰-Methenyl-THF also arises from N5-formimino-THF (see Fig. 20.4).] NADP(H) = nicotinamide adenine dinucleotide phosphate; NAD(H) = nicotinamide adenine dinucleotide; TMP = thymidine monophosphate; dUMP = deoxyuridine monophosphate; MTHFR = N⁵,N¹⁰-methylene-THF reductase.