Folate ( vitamin B9) – Source , Function

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Folate is a generic term which includes naturally occurring food folate and folic acid in supplements and fortified foods. Pteroylmonoglutamic acid and its derivatives are known as the folic acid group. Common structural features of the folate family include a pteridine bicyclic ring system, para-aminobenzoic acid (PABA) and one or more glutamic moieties .The term folic acid relates specifically to the fully oxidized monoglutamate form of the vitamin synthesized for commercial use in supplements and fortified foods. 

Food Source 

Folate occurs naturally in foods. Although folate is found in a wide variety of foods, it is present in a relatively low density except in the liver. Diets that contain adequate amounts of fresh green vegetables (i.e. in excess of twelve servings per day) will be good folate sources. Folate losses during harvesting, storage,’distribution and cooking can be considerable. Similarly, folate derived from animal products is subject to loss during cooking. Some staples, such as’ white rice are low in folate. 

  • Rich sources: Liver, dried yeast, leafy vegetables, wheat germ and rice polishings.
  • Good sources: Whole cereals, dried legumes (pulses have twice as much folic acid as cereals), nuts, fresh oranges, green leafy vegetables, 
  • Fair sources: Milled cereals, other vegetables, milk and fruits. 

It is important to remember that the natural folates found in foods are in a conjugated form, which reduces their bioavailability by perhaps as much as 50%. In addition, natural folates are much less stable. 

Absorption, Storage and Elimination

Folic acid is readily absorbed from the small intestines through the portal vein and passed into the tissues through general circulation. Naturally occurring food folate is converted into the monoglutamate form by the enzyme pteroyl polyglutamate hydrolase or folate conjugase or glutamate carboxypeptidase II, located in the jejunal brush border membrane. After deconjugation, the monoglutaniyl folate is transported across the membrane by a pH-dependent carrier-mediated mechanism.

Folic acid once absorbed is acted upon by hepatic dihydrofolate reductase to convert to its metabolically active form which is tetrahydrofolic acid (THF ). Following absorption, folic acid is largely reduced and methylated in the liver to ‘N-5 – methyltetrahydrofolic acid, which is the main transporting and storage form of folate in the body. Folate transport across membranes into cells in kidney, placenta and choroid plexus, occurs via membrane-associated folate binding proteins that act as folate receptors and facilitate cellular uptake of folate.

Larger doses of folate may escape metabolism by the liver and appear in the blood mainly as folic acid.

Function 

  • Folate in DNA synthesis

Folate, also known as folic acid, is essential for good health. Folate requiring reactions include those involved in phases of amino acid metabolism, DNA (purine and pyrimidine) biosynthesis and the formation of the primary methylating agent, S-adenosylmethionine (SAM).

Folate is involved in the DNA synthesis of purines (adenine and guanine), requiring the folate form, 10 formyl tetrahydrofolic acid (THF), which is produced from 5, 10-methylene THF reactions catalyzed by the enzyme THF synthetase. The 5,10- methylene THF molecule has several fates, one of which is the reconversion to 5- methyl THF, catalyzed by methylene tetra hydrojblate reductase (MTHFR).

Thus, folate in its reduced and polyglutamylated forms is essential for the DNA biosynthesis cycle. This conversion (5,10-methylene THF molecule reconversion to 5-methyl THF) forms methionine from homocysteine. Folate, especially helps in reducing the risk of heart disease and stroke by lowering the level of the amino acid homocysteine in the blood (by forming methionine).

At high levels, homocysteine can damage coronary arteries or make it easier for blood clotting cells to clump together and form a clot. This can increase the risk of heart attack or stroke. This methylation reaction requires the enzyme methionine synthase, cobalamin (vitamin B12) and 5-methyl THF.

 A methyl group is removed from 5 methyl THF and is sequentially transferred first to cobalamin coenzyme and then to homocysteine forming methionine and reconverting 5-methyl THF to tetrahydrofolate (THF). The dependency of methionine synthase on both folate and cobalamin explains why a single deficiency of either vitamin leads to the same megaloblastic changes in the bone marrow and other tissues, with rapidly dividing cells. 

Alternatively, 5,10-methylenetetrahydrofolate can be channeled to the methyltransferases cycle This cycle has two functions. It ensures that the cell always has an adequate supply of S-adenosyl methionine (SAM), an activated form of methionine which acts as a methyl donor to a wide range of methyltransferases. The methyltransferases methylate a wide range of substrates including lipids, hormones, DNA and proteins. One particularly important methylation is that of myelin basic protein, which acts as insulation for nerve cells.

When the methylation cycle is interrupted, as it is during vitamin B12 deficiency, one of the clinical consequences is the demyelination of nerve cells resulting in a neuropathy which leads to ataxia (lack of coordination), paralysis, and, if untreated, ultimately death. Other important methyltransferase enzymes down-regulate DNA and suppress cell division.

  • Folate In pregnancy 

Folate is also important for pregnant women. Low blood levels of folate during pregnancy can cause neural tube defects-anencephaly (a defect in the closure of the neural tube) and spina bifida (a congenital defect in which the spinal column is imperfectly closed so that part of the meninges or spinal cord protrudes, often resulting in hydrocephalus and other neurological disorders). And people with anaemia or at risk of anaemia need to be sure they consume enough folate as well. 

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