Folic Acid

• Overview

  • folic acid (folate, pteroylglutamate) structure
  • water-soluble vitamin, consisting of PABA (para-amino benzoic acid) with amino end attached to pteridine, and carboxyl end attached to a-amino group of glutamic acid
  • tetrahydrofolate (THFA, H4 folate)
  • active cofactor form of folic acid
  • formed by reduction of pteridine ring in positions 5, 6, 7, 8 by enzyme folic acid reductase
  • essential in metabolism because it donates carbon during purine, dTMP and methionine synthesis
• Folate Metabolism in Animals and Bacteria

  • folate is an essential substance in the body (organisms can’t survive without FA)
  • folate synthesis is inherent with bacteria through synthesis using pteridine, PABA and Glu
  • animals cannot synthesize folate, and therefore is needed to be incorporated in the diet
  • folate metabolism in bacteria are exploited in pharmacology
  • ability of bacteria to assimilate FA is the basis for making bacteria-selective sulfonamide antibiotics
  • sulfonamides are PABA analogs, which competes with PABA preventing folate synthesis
• THFA-mediated One-carbon Metabolism

  •  FA absorption in GIT requires removal of extra glutamates
  • reduction requires NADPH and FAR, and proceeds in two steps, to dihydrofolate and then to THFA
  • THFA picks up the one-carbon methylene group from serine (Ser) to form N5,N10-methylene-H4 folate, used in thymine synthesis or to be used as cofactor in methionine methylation
• Thymine Synthesis

  • thymine is the methylated form of uracil
  • important, as uracil is not found in DNA of prokaryotes and animals
  • if not synthesized, DNA synthesis cannot proceed and dTTP supply is insufficient
  • to control dTTP supply, animals have enzymes dUTPase to dephosphorylate dUTP to dUMP, and thymidylate synthase (TS) to methylate dUMP to dTMP