Vitamin B9 (Folic Acid)

Vitamin B9, commonly known as folic acid when synthesized for supplements, is a water‑soluble B‑vitamin that functions as a co-factor in one-carbon metabolism. Its primary purpose is to donate and accept single‑carbon units, which are essential for nucleic‑acid synthesis, amino‑acid metabolism, and the methylation of DNA, proteins, and lipids.

Folic acid (IUPAC: 5‑[(2‑S‑hydroxymethyl)‑4‑[[(2‑amino‑4‑oxo‑1,3‑dihydro‑2‑H‑pyrimidin‑5‑yl)‑methyl]‑amino]‑5‑oxo‑2‑pyridinecarboxylic acid) has the formula C₁₉H₁₉N₇O₆ (M = 441.4 g mol⁻¹). It comprises a pteridine ring, a para‑aminobenzoic acid (PABA) moiety, and a glutamate residue (p‑aminobenzoic acid linked via an amide to L‑glutamic acid). The molecule is amphoteric: the p‑carboxyl group (pKa ≈ 2.0) is de‑protonated at physiological pH, while the pterin nitrogen (pKa ≈ 5.0) remains partially protonated, giving folic acid modest water solubility (≈0.5 mg mL⁻¹). The reduced form, tetrahydrofolate, is the active co‑factor; the synthetic folic acid lacks the reduced pteridine ring and thus requires reduction by DHFR to become biologically active.

• Natural sources: Leafy greens (spinach, kale), legumes (lentils, peas), citrus fruits, and fortified grains contain naturally occurring folate as polyglutamate forms.
• Extraction: Folate is isolated from plant tissues via aqueous extraction, followed by enzymatic de-polymerization to monoglutamate (the form used in supplements).
• Synthetic production: Industrially, folic acid is synthesized chemically from p‑aminobenzoic acid and 2‑amino‑4‑hydroxy‑6‑methoxy‑pyrimidine, followed by condensation with L‑glutamic acid. This method yields >99 % purity and is the standard for pharmaceutical‑grade supplements.
• Quality considerations: USP‑NF or USP‑USP standards require ≥95 % purity, low heavy‑metal content, and stability testing (e.g., light and heat stability). Certifications such as GMP, ISO 9001, and third‑party testing (e.g., NSF, USP) ensure consistency and absence of contaminants such as cyanide or heavy metals.