Resumo de Folic Acid - Tracy W. Burke

This water soluble vitamin is essential for thebiosynthesis of RNA and DNA. It is also necessary for the growth andreproduction of all body cells. Folic acid (Folate) also helps in themetabolism of amino acids. Folic acid isa conjugated molecule consisting of a pteridine ring structure linked topara-aminobenzoic acid (PABA) that forms pteroic acid. Folicacid itself is then generated through the conjugation of glutamic acid residuesto pteroic acid. Folic acid is obtained primarily from yeasts and leafyvegetables as well as animal liver. Animal cannot synthesize PABA nor attachglutamate residues to pteroic acid, thus, requiring folate intake in the diet.When stored in the liver or ingested folic acid exists in a polyglutamate form.Intestinal mucosal cells remove some of the glutamate residues through theaction of the lysosomal enzyme, conjugase. The removal of glutamate residuesmakes folate less negatively charged (from the polyglutamic acids) andtherefore more capable of passing through the basal lamenal membrane of theepithelial cells of the intestine and into the bloodstream. Folic acid isreduced within cells (principally the liver where it is stored) totetrahydrofolate (THF also H4folate) through the action ofdihydrofolate reductase (DHFR), an NADPH-requiring enzyme. The function of THFderivatives is to carry and transfer various forms of one carbon units during biosyntheticreactions. The one carbon units are either methyl, methylene, methenyl, formylor formimino groups. These one carbon transfer reactions are required in thebiosynthesis of serine, methionine, glycine, choline and the purine nucleotidesand dTMP. The ability to acquire choline and amino acids from the diet and tosalvage the purine nucleotides makes the role of N5,N10-methylene-THFin dTMP synthesis the most metabolically significant function for this vitamin.The role of vitamin B12 and N5-methyl-THF in theconversion of homocysteine to methionine also can have a significant impact onthe ability of cells to regenerate needed THF. A defficiency in Folate can result in complications nearly identical tothose described for vitamin B12 deficiency. The most pronouncedeffect of folate deficiency on cellular processes is upon DNA synthesis. Thisis due to an impairment in dTMP synthesis which leads to cell cycle arrest inS-phase of rapidly proliferating cells, in particular hematopoietic cells. Theresult is megaloblastic anemiaas for vitamin B12 deficiency. The inability to synthesize DNAduring erythrocyte maturation leads to abnormally large erythrocytes termed macrocytic anemia. Folate deficienciesare rare due to the adequate presence of folate in food. Poor dietary habits asthose of chronic alcoholics can lead to folate deficiency. The predominantcauses of folate deficiency in non-alcoholics are impaired absorption ormetabolism or an increased demand for the vitamin. The predominant conditionrequiring an increase in the daily intake of folate is pregnancy. This is dueto an increased number of rapidly proliferating cells present in the blood. Theneed for folate will nearly double by the third trimester of pregnancy. Certaindrugs such as anticonvulsants and oral contraceptives can impair the absorptionof folate. Anticonvulsants also increase the rate of folate metabolism.

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