Folic acid Lecture Folate Biochemistry Prof.Dr.Hussein Kadhem Al-Hakeim, فيتامين بي 9 حمض الفوليك

Folic Acid (Vitamien B9)
• Folic acid is obtained primarily from yeasts and leafy vegetables as well as animal liver.
• Folic acid is reduced within cells (principally the liver where it is stored) to tetrahydrofolate (THF also H4folate) through the action of dihydrofolate reductase (DHFR), an NADPH-requiring enzyme.

Folic Acid
positions 7 & 8 carry hydrogens in dihydrofolate (DHF)
positions 5-8 carry hydrogens in tetrahydrofolate (THF)
• The function of THF derivatives is to carry and transfer various forms of one carbon units during biosynthetic reactions. The one carbon units are either methyl, methylene, methenyl, formyl or formimino groups.

Active center of tetrahydrofolate (THF). Note that the N5 position is the site of attachment of methyl and formimino groups. N10 the site for attachment of formyl and and that both N5 and N10 bridge the methylene and methenyl groups.
• These one carbon transfer reactions are required in the biosynthesis of serine, methionine, glycine, choline and the purine nucleotides and dTMP.
Clinical Significance of Folate Deficiency
Folate deficiencies are rare due to the adequate presence of folate in food
a) The most pronounced effect of folate deficiency on cellular processes is upon DNA synthesis. This is due to an impairment in dTMP synthesis which leads to cell cycle arrest in S-phase (Synthesis Phase, is the phase of the cell cycle in which DNA is replicated) of rapidly proliferating cells, in particular hematopoietic cells. The result is megaloblastic anemia as for vitamin B12 deficiency.
b) The inability to synthesize DNA during erythrocyte maturation leads to abnormally large erythrocytes termed macrocytic anemia.