Folic acid and Amino acid Metabolism

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, the dehydrated form of carbonic acid, 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 phosphates (NADPH). The one-carbon unit carried by THF is bound to nitrogen N⁵ or N¹⁰ or to both N⁵ and N¹⁰. Figure 20.11 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 due to decreased availability of the purines and of the thymidine monophosphate needed for DNA synthesis.]

Figure 20.11 Summary of the interconversions and uses of the carrier tetrahydrofolate. [Note: N⁵, N¹⁰-Methenyl-THF also arises from N⁵-formimino-THF (see Figure 20.4).] NADP(H) = nicotinamide adenine dinucleotide phosphate; NAD(H) = nicotinamide adenine dinucleotide; TMP = thymidine monophosphate; dUMP = deoxyuridine monophosphate.