Title:The Medicinal Chemistry of Nitrite as a Source of Nitric Oxide Signaling
Volume: 17
Issue: 15
Author(s): Arlin B. Blood*
Affiliation:
- 11175 Campus Street, Coleman 11121, Loma Linda, CA 92354,United States
Keywords:
Nitrite, Nitrate, nitric oxide, nitrosothiol, iron-nitrosyl, dinitrosyl iron complex.
Abstract: Conventional understanding of nitric oxide (NO) signaling in biology is commonly based
on the premise that it simply diffuses randomly from its site of production by NO synthases to its site
of action or inactivation. This notion has been challenged on a systemic cardiovascular scale with the
realization that NO has endocrine effects despite being unable to exist in blood for more than a few
milliseconds. Investigation of this phenomenon has led to the understanding that many of the chemical
pathways that consume NO may not render it inactive as once thought. Instead, many of NO’s
metabolic products are still capable of carrying out NO signaling, or participate in NO-independent
signaling in their own right.
Nitrite and nitrate are two such products of NO metabolism that were once thought to be inert at
physiological concentrations but are now known to contribute to NO bioactivity. The activity of nitrate
is dependent upon its reduction to nitrite by bacterial nitrate reductase activity in the mouth. Nitrite
can be reduced to NO by several metal-containing proteins under hypoxic conditions, or by nonenzymatic
reactions under acidic conditions. Reduction and oxidation products of nitrite metabolism
may also result in the production of NO adducts with a wide array of biological functions. The following
review provides a general overview of the basic pathways underlying the physiological activity
of nitrate and nitrite, as well as insight into the therapeutic potential of these pathways.