45. Tetrahydrofolate as a carrier of “C1”-One-Carbon-Units. Role of Folic Acid. Antifolate Drugs. Importance of SAM.
Covers tetrahydrofolate as the carrier of one-carbon units in forms such as methyl, methylene and formyl, and where these units come from. It then looks at the reactions that need them, including purine synthesis, dTMP formation and methionine regeneration, followed by the clinical role of folic acid. A table lists the one-carbon forms of THF, and the note goes on to antifolate drugs such as methotrexate, trimethoprim and pyrimethamine, and ends with the synthesis and methyl-donor role of SAM.
Topic 45 of 76 in the MU Pleven syllabus for Biochemistry (Medicine, Year 2). The free AceMed note covers it in 6 sections, about 609 words (5 min of reading), with 10 flashcards.
In this note
Tetrahydrofolate as a carrier of “C1”-One-Carbon-Units. Role of Folic Acid. Antifolate Drugs. Importance of SAM.
Tetrahydrofolate (THF) as a Carrier of One-Carbon (C1) Units
Reactions Requiring THF (Where It Carries C1 Units)
Role of Folic Acid (Why It Matters Clinically)
Antifolate Drugs (Target THF Pathway)
Importance of S-Adenosyl Methionine (SAM)
Tetrahydrofolate (THF) as a Carrier of One-Carbon (C1) Units
Folic acid (Vitamin B9) is taken in the diet in an oxidized form.
In the body, it is converted to dihydrofolate (DHF) and then to tetrahydrofolate (THF) by the enzyme Dihydrofolate Reductase (DHFR).
THF is the active form that can carry and transfer single-carbon fragments (C1 units) in various oxidation states.
These C1 units may be: methyl (–CH3), methylene (–CH2–), formyl (–CHO), formimino, methenyl, etc.
THF collects these one-carbon groups mainly from:
Serine and Glycine metabolism
Histidine metabolism
Tryptophan metabolism
It then donates these C1 units for important biosynthetic reactions.
Reactions Requiring THF (Where It Carries C1 Units)
Purine nucleotide synthesis
THF provides carbon atoms for the adenine and guanine ring structure.
Thymidine (dTMP) synthesis
THF donates a methyl group for conversion of dUMP → dTMP (via Thymidylate Synthase).
Essential for DNA synthesis and cell division.
Methionine synthesis
THF helps regenerate methionine from homocysteine (requires Vitamin B12).
Role of Folic Acid (Why It Matters Clinically)
Needed for DNA synthesis, particularly in rapidly dividing cells:
Bone marrow (RBC production)
GI mucosa
Embryonic tissues
Deficiency leads to:
Megaloblastic anemia (large, immature RBCs due to impaired DNA synthesis)
Hypersegmented neutrophils
Neural tube defects in fetus (spina bifida, anencephaly)
Pregnant women require increased folate supplementation.
Alcoholics commonly have deficiency due to poor intake and absorption.
ROLE OF FOLIC ACID (WHY IT MATTERS CLINICALY)
DIETARY FOLIC ACID / SUPPLEMENTS → Reduced to Tethahrodofoltate (THF) → ONE-CARBON UNIT TRANSFER → SYNTHESIS OF AMINO ACIDS / NUCLLIC ACIDS
DIETARY FOLIC ACID / SUPPLEMENTS → DNA SYNTTESIS (Purines & dtMP) → CELL PROFULERATION (Especially Rapidly Diviing Cells) → CRUCIAL FOR FETAL DEVELOPMENT
