Arginases and arginine deficiency syndromes.
OBJECTIVE
Many physiologic and pathophysiologic processes are modulated by arginine availability, which can be regulated by arginase. An understanding of the conditions that result in elevated arginase activity as well as the consequences of arginine deficiency is essential for design of effective nutritional support for disease. This review will emphasize recent findings regarding effects of plasma arginase and arginine deficiencies in disease.


RESULTS
Elevations in plasma arginase, derived primarily from hemolysis of red blood cells or liver damage, that are associated with arginine deficiency have been identified in an increasing number of diseases and conditions. Arginine insufficiency not only can activate a stress kinase pathway that impairs function of T lymphocytes but it also can inhibit the mitogen-activated protein kinase signaling pathway required for macrophage production of cytokines in response to bacterial endotoxin/lipopolysaccharide.


CONCLUSIONS
There are at least two broad categories of arginine deficiency syndromes, involving either T-cell dysfunction or endothelial dysfunction, depending on the disease context in which arginine deficiency occurs. There is limited information regarding the safety and efficacy of supplementation with arginine or its precursor citrulline in ameliorating arginine deficiency in specific diseases, indicating the need for further studies.
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. smorris@pitt.edu
Sidney M
SM
Morris
D001119:Arginase / Q000097:blood*; D001120:Arginine / Q000172:deficiency*; D016207:Cytokines / Q000096:biosynthesis*; D003677:Deficiency Diseases / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism*; D015398:Signal Transduction; D013577:Syndrome; D013601:T-Lymphocytes / Q000378:metabolism*
D016207:Cytokines; D001120:Arginine; D010770:Phosphotransferases; D001119:Arginase