Molecule of the Day: Folic acid
Folic acid (C19H19N7O6), also known as Vitamin B9, is a yellow powder that is insoluble in water under standard conditions. It is essential to metabolism and cell division, and is found in many fruits and vegetables.
Folic acid (in the form of tetrahydrofolate [THF], a metabolite) plays an integral role in methylation and other metabolic reactions by carrying one-carbon groups that react with other substrates. Additionally, it also is a key intermediate in the synthesis of purines and hence DNA via N10-formyl-THF (see diagram below).
It is also essential in the process of cell division, since the methylation and demethylation of DNA, which controls gene expression, and the synthesis of nitrogenous bases, which is required for DNA replication, are absolutely key to this process.
Folic acid is commonly found as a food additive, as it lowers the probability of neural tube defects occurring in pregnant women. These are characterised by openings in the spinal cord or brain which fail to close during pregnancy, and can result in the death of the foetus. Hence, the fortification of cereal grains and other foods with folic acid is mandated by many governments.
The inhibition of dihydropteroate synthase, an enzyme that synthesises tetrahydrofolate, is one of the key mechanisms that antibacterial agents can target. Sulfonamides, which are similar in structure to 4-aminobenzoic acid, the natural substrate, are reversible inhibitors of the enzyme. As a result, insufficient folic acid is produced in bacteria, and they either stop dividing or die.
This makes sulfonamides seem dangerous - wouldn’t this affect human cells as well? However, bacterial cells produce their own folic acid, whereas human cells do not; instead, we absorb it from our diet, while bacterial cells lack the ability to do so. As a result, sulfonamides selectively kill bacterial cells, leaving our cells intact and healthy.