Nitrate Metabolism: A Curse or Blessing to Humanity?

Nitrate (NO3ˉ) is a metabolic waste produced in humans during the detoxification of nitric oxide (NO). Nitric oxide is responsible for the regulation of blood flow, cell signaling and host defense in a number of mammalian tissues. Shortly after synthesis, nitric oxide is oxidized to nitrate in order to terminate its effect. NO can also be synthesized by an alternative mechanism that relies on the sequential reduction of nitrate to nitrite (NO2ˉ); thereby making nitrite a storage pool that can be reduced to NO under appropriate condition with a concomitant increase in the methemoglobin (metHb) concentration. The NO and metHb produced can result to adverse health effects if not detoxified. NADH-methemoglobin reductase accounts for most metHb reduction. Nitric oxide dioxygenases (NODs) catalyze the conversion of NO to NO3ˉ­­­­­ which help to protect cells from NO poisoning. Nitrate and its reduction products are involved in the modification of the body’s physiological functions. We are exposed to nitrate from dietary intake and nitric oxide oxidation. Nitrate metabolism becomes a threat when nitrate is consumed in excess and the body lacks the enzymes that catalyze the detoxification of its byproducts. During such condition, the hemoglobin, nucleic acids, dietary amines and glycoproteins acts as the primary molecule that mediates its effects. Nitrate is a potential therapeutic agent in the prevention of cardiovascular diseases and improving cell viability. This review serves to reevaluate nitrate metabolism in human with the intentions of understanding its role in NO homeostasis and its metabolic effect due to excess intake.