What is one-carbon metabolism and why is it important?

One-carbon metabolism transfers single-carbon units for biosynthesis and methylation reactions. The folate cycle carries one-carbon units on tetrahydrofolate (THF) in various oxidation states: methyl (CH3-THF), methylene (CH2-THF), and formyl (CHO-THF). These support: thymidylate synthesis (DNA), purine synthesis, methionine regeneration, and homocysteine remethylation. The methionine cycle generates S-adenosylmethionine (SAM), the universal methyl donor for >100 methyltransferases affecting DNA, histones, neurotransmitters, and lipids. Vitamin B12 is required for methionine synthase. Folate deficiency causes megaloblastic anemia and neural tube defects; impaired methylation affects epigenetics and neurotransmission. Antifolates (methotrexate) target this pathway in cancer.