An Assessment on the Metabolism of Folate

METABOLISM OF FOLATE

Metabolism of Folate

Bailey and Gregory suggest that reactions that require folate occur as a one-carbon metabolism. Essentially, a polyglutamyl which happens to be in form of tetrahydrofolate (THF) is the central folate acceptor. In these processes, the main function of folate happens to be donation and acceptance of one carbon units in metabolic pathways.1 The first step in metabolism involves the conversion of tetrahydrofolate to 5, 10-methyltetrafolate. The said step is important in metabolism which uses the 3- carbons from serine as their source of carbon. 5, 10-methyltetrahydrofolate is then transferred to tetrahydrofolate from serine through the pyridoxal phosphate (PLP). PLP is a dependent serine hydromethyltransferase (SHMT) which forms glycine and 5, 10 methylene-TPF.1 Part of the 5, 10 methylenetetrahyhrofolate which was produced is then reduced by methylenetetrahydrofolate reductase (MTHFR) through an irreversible enzymatic reaction to 5-methyl-THF. MTHFR is only used in metabolism to methylation in synthesis of homocysteine. More than 50% of homocysteine which is generated is remethylated dependent upon the content of choline and methionine in the diet.1 In methionine synthesis, a methyl group from 5-methyl-THF is removed and transferred to vitamin B-12 prior homocysteine to form methionine. Methionine synthesis is also involved in regeneration of THF which is used in formation of 10-formyl-THF and 5, 10-methylene-THF which are used in purine and thymidylate synthesis. It is important to note that folate is involved in various biochemical processes and thus its metabolism is crucial for the said processes. The said biochemical processes are inclusive of, but they are not limited to; methionine regeneration, mitochondrial protein translation, thymidine monophosphate biosynthesis, and purine synthesis.2 The said processes are important in humans given that they support crucial cellular processes which are inclusive of, but they are not limited to; epigenetic regulation, mitochondrial respiration, cell proliferation, and homeostasis.1,2

As was explained earlier, folate is an essential vitamin in biochemical processes. Therefore, when its amount is lower than the normal amount in the blood, then it means that there is a deficiency. There are various causes of folic acid deficiency. To begin with, Khan and Jialal found that folic deficiency is caused by inadequate intake of folic acid in the diet.3 Second, when food is heated during cooking, the folic acid in the food is destroyed. Third, during active and passive mechanisms in the small intestines, the jejunum absorbs folate. Therefore, diseases which are inclusive of, but they are not limited to gastric bypass, amyloidosis, short bowel syndrome, and celiac disease cause deficiency by inhibiting the absorption of folate.3 In addition, drugs such as trimethoprim, sulfasalazine, phenytoin, and methotrexate can cause folate deficiency by antagonizing its utilization, thus inhibiting its conversion or absorption. Further, folate metabolism requires congenital enzymes, and their deficiencies causes deficiency of folate.3 Folate deficiency can also result from its excretion in urine owing to deficiency of vitamin B-12. Essentially, when methionine synthase is impaired, it causes the folate in the blood to be trapped in form of methyltetrahydrofolate which builds in the serum trapping folate.3 Conditions such as hemolytic anemia, pregnancy, and alcoholism can also cause deficiency of folate in the blood.

Deficiency of folate in humans is associated with various consequences. During pregnancy, lack of folate may lead to an increased risk of diabetes which may be associated with autism and congenital disabilities such as neural tube defects.1,3 Apart from the said disabilities, folate deficiency is associated with pregnancy complications which are inclusive of, but they are not limited to; severe language deficits, spontaneous abortion, and placenta abruption. It is important to note that when folate is trapped as methyltetrahydrofolate, it results to impartment of methylation reactions which are required in the process of regulating gene expression. In addition, the said trapping leads to accumulation of toxic metabolites and impairment of cell division.3 Deficiency of folate may also lead to macrocytic anemia. Essentially, deficiency of folic acid in the blood leads to a decrease in hematocrit and hemoglobin leading to anemia. Moreover, deficiency of folate may lead to increased risk of some types of cancer. If left untreated, it is important to note that the said deficiency can result to psychosis, fatigue, cognitive decline, insomnia, irritability, depression, oral ulcers, angular stomatitis, glossitis, pancytopenia, and megaloblastic anemia.3 To a large extent, the knowledge we have at present about these processes described above could be used towards the betterment of human wellbeing. As has been pointed out in Is. 48:17, this knowledge has been given to us by God for our own good.