Arginase: an old enzyme with new tricks.
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.
Veterans Affairs Medical Center, One Freedom Way, Augusta, GA 30904, USA; Vision Discovery Institute, Medical College of Georgia, Georgia Regents University, 1459 Laney Walker Boulevard, Augusta, GA 30912, USA; Vascular Biology Center, Medical College of Georgia, Georgia Regents University, 1459 Laney Walker Boulevard, Augusta, GA 30912, USA. Electronic address: rcaldwel@gru.edu.
Ruth B
RB
Caldwell
Department of Pharmacology and Toxicology, Medical College of Georgia, Georgia Regents University, 1459 Laney Walker Boulevard, Augusta, GA 30912, USA.
Haroldo A
HA
Toque
Vision Discovery Institute, Medical College of Georgia, Georgia Regents University, 1459 Laney Walker Boulevard, Augusta, GA 30912, USA; Vascular Biology Center, Medical College of Georgia, Georgia Regents University, 1459 Laney Walker Boulevard, Augusta, GA 30912, USA; Department of Occupational Therapy, School of Allied Health Sciences, Medical College of Georgia, Georgia Regents University, 1459 Laney Walker Boulevard, Augusta, GA 30912, USA.
S Priya
SP
Narayanan
Vision Discovery Institute, Medical College of Georgia, Georgia Regents University, 1459 Laney Walker Boulevard, Augusta, GA 30912, USA; Department of Pharmacology and Toxicology, Medical College of Georgia, Georgia Regents University, 1459 Laney Walker Boulevard, Augusta, GA 30912, USA. Electronic address: wcaldwel@gru.edu.
R William
RW
Caldwell
D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D009422:Nervous System Diseases / Q000201:enzymology / Q000378:metabolism*; D018384:Oxidative Stress
D001119:Arginase
arginase; neurodegeneration; nitric oxide; oxidative stress; peroxynitrite; polyamine; superoxide; vascular dysfunction