Nitrite-NO bailout for a NOS complex too big to fail

Cellular production of nitric oxide (NO) by nitric oxide synthase (NOS) in the face of limiting pools of arginine requires the intracellular citrulline-to-NO pathway, catalyzed by the enzyme argininosuccinate lyase (ASL). People with the urea cycle disorder argininosuccinic aciduria, caused by a deficiency of ASL, have systemic NO deficiency, which can be rescued by the use of an alternative, NOS-independent, nitrite-to-NO pathway.