New Doc 11-20-2024 20.15 (3)

Chapter 38: Water Soluble Vitamins - Folic Acid, Vitamin B, and Ascorbic Acid

Overview

  • Focus on the role of:

    • Folic Acid

    • Choline

    • Vitamin B

    • Ascorbic Acid (Vitamin C)

Folic Acid

  • Derived from the Latin word "folium," meaning leaf.

  • Importance of transporters and binding proteins for absorption.

  • Structure and Chemistry:

    • Composed of three components:

      • Pteridine group

      • Para-aminobenzoic acid (PABA) - refers to pteroic acid.

      • Glutamic acid

    • Folic acid is first reduced to Tetrahydrofolate (THFA) by NADPH dependent folate reductase.

    • Natural forms exist as polyglutamates (up to seven glutamate residues attached).

    • Soluble in water but sensitive to light.

Absorption of Folic Acid

  • Location: Upper part of the jejunum.

  • Transport: Carried in the blood by beta globulins and taken up by the liver to produce co-enzymes.

  • Note: Folic acid is not stored in tissues.

Page 2: Deficiency Manifestations

  • Deficiency Effects:

    • Increased plasma homocysteine levels associated with coronary artery disease.

    • Low levels of THFA inhibit thymidylate synthase, preventing conversion of dUMP to dTMP for DNA synthesis.

    • Rapidly dividing cells in bone marrow and intestinal mucosa are most affected, leading to:

      • Birth defects - particularly neural tube defects during pregnancy.

      • Macrocytic Anemia - characterized by delayed DNA synthesis and asymmetry in RBC precursors.

Symptoms of Folate Deficiency

  • Features include:

    • Hemolysis and reticulocytosis (increased immature RBCs).

    • Peripheral blood picture indicates macrocytic anemia.

    • Often leads to leukopenia and thrombocytopenia.

Assessment of Folate Deficiency

  • Methods:

    1. Blood Levels: Normal level is between 20 ng/mL and 200 µg/mL.

      • Measured by radioimmunoassay.

    2. Histidine Load Test: Assess FIGLU excretion in urine.

    3. AICAR Excretion: Blockage leads to increased urination of precursor AIC in purine synthesis.

Page 3: Sources of Folic Acid

  • Rich Sources: Yeast, green leafy vegetables.

  • Moderate Sources: Cereals, pulses, oilseeds.

  • Poor Sources: Milk.

  • Recommended Daily Allowance (RDA):

    • 200 µg/day for adults.

    • 400 µg/day for pregnant women.

    • 300 µg/day for breastfeeding women.

Summary of Folic Acid Importance

  • Crucial for DNA synthesis and maintaining cell division, particularly for rapidly dividing cells.

  • Role in cancer prevention, with implications for various carcinomas.

Page 4: Therapy and Folate Antagonists

  • Folate Therapy: Used to prevent diseases; consider potential nerve damage.

  • Chemistry of Folate Antagonists:

    • Sulfonamides: Compete with PABA, inhibiting folic acid synthesis in bacteria.

      • Structural similarity to PABA.

      • Discovered by Gerhard Domagk (1932), awarded Nobel Prize.

    • Pyrimethamine: Antimalarial drug, competitive THFA inhibition.

    • Aminopterin and Amethopterin (methotrexate): Competitive inhibitors of THFA generation and cell formation.