Arginase: an old enzyme with new tricks

• Arginase is the enzyme that converts L-arginine to urea and L-ornithine, functions important for protection against NH3 toxicity and for cell growth and repair.
• Excessive arginase activity has been linked to cardiovascular diseases because it reduces the supply of L-arginine needed by nitric oxide (NO) synthase to produce NO.
• Excessive activity of the arginase/ornithine pathway can also contribute to vascular structural problems and neural toxicity.
• Recent research has identified inflammatory agents and reactive oxygen species as drivers of the pathologic elevation of arginase activity and expression.

Arginase has roots in early life-forms. It converts L-arginine to urea and ornithine. The former provides protection against NH3; the latter serves to stimulate cell growth and other physiological functions. Excessive arginase activity in mammals has been associated with cardiovascular and nervous system dysfunction and disease. Two relevant aspects of this elevated activity may be involved in these disease states. First, excessive arginase activity reduces the supply of L-arginine needed by nitric oxide (NO) synthase to produce NO. Second, excessive production of ornithine leads to vascular structural problems and neural toxicity. Recent research has identified inflammatory agents and reactive oxygen species (ROS) as drivers of this pathologic elevation of arginase activity and expression. We review the involvement of arginase in cardiovascular and nervous system dysfunction, and discuss potential therapeutic interventions targeting excess arginase.