Folate (Vitamin B9) deficiency

Folate deficiency is a clinical condition that occurs because of low level of folate or folic acid in the body. This can lead to a variety of problems ranging from anemia in individuals from all age groups to neural tube malformation in fetuses.

Folate, also known as vitamin B9, mainly comes from eating leafy greens and citrus fruits like oranges and lemons and, nowadays, many countries fortify foods like grains and cereals with folate.

Now, folic acid present in these food items is generally in polyglutamate form, which are basically chains of an amino acid called glutamic acid.

Because of the carboxyl group present in its structure, the chain is negatively charged making it polar and soluble in water, which is a polar molecule but not soluble in lipids which are nonpolar molecules.

So the polyglutamate residues of folic acid are almost non-absorbable from the GI tract, where all the cells are surfaced with lipid cell membranes.

So, to make them absorbable, when polyglutamate residues reach a portion of the small intestine called the jejunum, special enzymes present at the jejunal mucosa cut down the polyglutamate residues into monoglutamate.

Monoglutamate is smaller, and is less negatively charged, so these monoglutamate residues of folic acids can pass through the cell membrane and enter the jejunal cells, where they are converted into tetrahydrofolic acid or in short THF by the enzyme tetrahydrofolate reductase.

These THFs then get methylated into a more stable form called methyl-THF. Once formed, the methyl-THF then leaves the jejunal cell and enters the bloodstream.

Some of it goes to the liver and get stored for a short period of 2-3 months, while most of it is used up for metabolic activity inside various cells around the body.

Folic acid is used to synthesize DNA precursors, which is essential for DNA replication and cell division.

On target cells, there’s a specialized membrane protein called Folic Acid Transporter or FAT, which moves the circulating methyl-THF inside the cell.

Once inside, methyl-THF transfers its methyl group to vitamin B12, ultimately making methylcobalamin and free THF in the process.

THF then gets an extra “methylene” group from serine, an amino acid found within the cells.

THF quickly transfers the methylene to a nucleotide called deoxyuridine monophosphate, or d-UMP for short. As a result, d-UMP becomes d-TMP or deoxythymidine monophosphate, which can then be converted to thymidine, one of the nucleotides used to build DNA.