ABSTRACT

Arginine is an amino acid which is not considered essential for adult mammals as it can be synthesized in vivo via urea cycle intermediates. Arginine plays an important role in protein synthesis, urea cycle metabolism and the synthesis of the high-energy compounds, creatine and creatine phosphate. Two pathways of arginine metabolism have been identified as potential sources of critical mediators of arginine immunomodulatory actions in vivo. The so-called “arginase” pathway, in which arginine is converted to urea and ornithine, generates polyamines by the action of ornithine decarboxylase on the latter compound. This route of polyamine synthesis was proposed as the mechanism whereby arginine augments lymphocyte mitogenesis.2 Induction of arginase was also proposed as the effector pathway in arginine-dependent macrophage-mediated tumor cell cytotoxicity.3 A second more recently described pathway of arginine metabolism leads to the generation of reactive nitrogen intermediates-principally nitric oxide and its peroxynitrite derivatives. These reactive nitrogen intermediates are derived from arginine through the action of nitric oxide synthase.4 It is postulated that macrophage-mediated tumor cytotoxicity and fungistasis are mediated through this pathway.5 Over the last few years, extensive research has been conducted on the biology and pathology of nitric oxide and its role in cellular metabolism. Nitric oxide serves as a messenger in the central and peripheral nervous system and as a mediator of cerebral hypoxic injury under ischemic conditions.6,7 In the vascular endothelium nitric oxide is thought to be the active moiety of the endothelium-derived relaxation factor which mediates vascular vasodilatation.8 Nitric oxide is

Nutritional Support in Cancer and Transplant Patients, edited by Rifat Latifi and Ronald C. Merrell. ©2001 Eurekah.com.