An Additional, Complementary Mechanism of Action for Folic Acid in the Treatment of Megaloblastic Anemia

Bruce K Kowiatek*

Received: November 01, 2018;   Published: November 20, 2018

DOI: 10.26717/BJSTR.2018.11.002071

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Abstract

Administration of supplemental folic acid addresses the impaired DNA synthesis causing megaloblastic anemia; however, despite the possibility of high doses of folic acid -5 to 15 milligrams (mg) daily for up to four months -the extremely rapid initial onset of action -30 to 60 minutes -when administered orally is not in keeping with the accepted mechanism, which can take up to nearly 22 hours, even under enzymatic control. This would suggest an additional, complementary non-enzymatic mechanism of nucleotide methylation at work; it is, therefore, proposed here, with in vitro evidence put forth, that rapid, non-enzymatic methylation by folic acid, via 5,10-methylenetetrahydrofolate and 7,8-tetrahydrofolate intermediates, of deoxyuridine monophosphate to form thymidylate using the cell membrane phospholipid phosphatidylcholine as a methyl donor, leaving de-methylated phosphatidylethanolamine, is a viable additional and complementary mechanism in helping reduce megaloblastic red blood cells to normal size and function.

Keywords : Folic Acid; DNA; Megaloblastic Anemia; Deoxyuridine Monophosphate; Thymidylate

Abbreviations : PC: Phosphatidylcholine; DUMP: Deoxyuridine 5′-Monophosphate; DHFR: Dihydrofolate Reductase; THF: Tetrahydrofolate; dTMP: Deoxythymidine 5′-Monophosphate; SAM-e: S-Adenosylmethionine; PE: Phosphatidylethanolamine; TMS: Trimethylsilyl; PCCA: Professional Compounding Centers of America; NS: Normal Saline; HCL: Hydrochloric Acid