Vitamin B7 (Biotin) and Vitamin B9 (Folic Acid)

Mechanism

🥚 Vitamin B7 (Biotin)

• Mechanism: Covalent binding to lysine residues of cellular carboxylase enzymes (Biotinylation).
• Key Routes: Gluconeogenesis (pyruvate carboxylase) and lipid synthesis (acetyl-CoA carboxylase).
• Ingestion of raw avidin present in egg white inactivates its intestinal absorption.

🍀 Vitamin B9 (Folic Acid)

• Active Form: Cellular reduced tetrahydrofolate (THF).
• Key Routes: De novo synthesis of purine and thymidine nucleotides for DNA synthesis.
• Essential for early closure of the neural tube in embryonic development.

Dynamics of purine synthesis by folic acid

Folic acid or dietary folate monoglutamate is reduced intracellularly in a two-stage manner in the enterocyte by the enzyme Dihydrofolate Reductase (DHFR) using coenzyme NADPH to generate the functional tetrahydrofolate (THF):

THF captures monocarbon groups (methyl, methylene, formyl) to act as a transporter in cellular synthesis:

• N5,N10-Methylene-THF: Donor of the cellular methyl group necessary to convert dUMP to dTMP by the mitochondrial enzyme thymidylate synthase, the limiting step for cellular DNA duplication.
• N5-Methyl-THF: Predominant circulating cellular form that transfers its methyl group to homocysteine to regenerate methionine, a vitamin B12-dependent reaction.

MTHFR Mutation and the Folate Trap Phenomenon

The enzyme Methylenetetrahydrofolate Reductase (MTHFR) irreversibly converts N5,N10-methylene-THF into N5-methyl-THF. Common polymorphisms of this enzyme (677C→T) reduce its catalytic activity, limiting cellular regeneration of methionine and causing the accumulation of serum homocysteine (hyperhomocysteinemia), a risk factor for vascular endothelial thrombosis.

Indicators and dose

Clinical Indications and Prevention of Neural Tube

• Prevention of Neural Tube Defects (NTD) in Pregnancy: The physiological closure of the embryonic neural tube occurs between days 21 and 28 post-conception. Cell division requires massive folate-dependent rates of cell replication. 400 µg daily of folic acid is universally prescribed to all women of childbearing age planning pregnancy, starting one month before pregnancy and continuing during the first trimester. In women with a history of previous NTD or with anticonvulsant treatment, the dose is increased to 4-5 mg daily.
• Macrocytic Megaloblastic Anemia: The delay in the synthesis of DNA nucleotides with respect to protein cytoplasmic maturation generates giant and ineffective erythroid precursors in the bone marrow.