Mechanism
Recent discoveries in the field of nitrate and nitrite biology not only emphasized on understanding their potential beneficial roles, but have also shed light on mechanistic insights. Thus, better understanding of biology of NO synthesis has further helped nutritionists and health professionals in realizing the importance of dietary nitrate and nitrite, especially in the field of sports and exercise.
It was believed that ‘NO’ — a ubiquitous physiological signaling molecule, was synthesized exclusively via oxidation of L-arginine—resulting in the endogenous production of nitrate and nitrite, a reaction that is catalyzed by a family of NO synthase (NOS) enzymes. However, an alternative ‘nitrate–nitrite–NO’ pathway has been discovered recently, wherein, nitrate and nitrite can be reduced back to NO and other bioactive nitrogen oxides in vivo.
This pathway complements the conventionally believed ‘L-arginine–NOS–NO’ pathway, especially in conditions of oxygen deficiency in which NOS activity, which is oxygen-dependent, may be reduced—helps facilitate NO synthesis.
Apart from endogenous NOS system, exogenously dietary intake of various green leafy vegetables also helps the body to store nitrate and nitrite.
Physiologically, it is believed that dietary nitrate is absorbed rapidly from the stomach and small intestine, and ~25% of ingested nitrate enters the entero-salivary circulation, where it gets reduced to nitrite by bacterial nitrate reductases from symbiotic anaerobic bacteria on the surface of the tongue.
Further, this nitrite is either reduced to NO in the acidic environment of the stomach or is absorbed via the gastrointestinal tract and re-enters the circulation.
Biological Pathways of NO synthesis
(Reproduced from: Jones AM., Sports Med. 2014)
This pathway complements the conventionally believed ‘L-arginine–NOS–NO’ pathway, especially in conditions of oxygen deficiency in which NOS activity, which is oxygen-dependent, may be reduced—helps facilitate NO synthesis.
Apart from endogenous NOS system, exogenously dietary intake of various green leafy vegetables also helps the body to store nitrate and nitrite.
Physiologically, it is believed that dietary nitrate is absorbed rapidly from the stomach and small intestine, and ~25% of ingested nitrate enters the entero-salivary circulation, where it gets reduced to nitrite by bacterial nitrate reductases from symbiotic anaerobic bacteria on the surface of the tongue.
Further, this nitrite is either reduced to NO in the acidic environment of the stomach or is absorbed via the gastrointestinal tract and re-enters the circulation.
Biological Pathways of NO synthesis
(Reproduced from: Jones AM., Sports Med. 2014)
It has also been found that numerous enzymes and proteins, including deoxyhemoglobin, are involved in the reduction of nitrite to NO in blood and other tissues. This course of action takes place predominantly in conditions of low oxygen availability (e.g. ischemia and hypoxia) and low pH—enabling NO synthesis, where it is most required.