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Supplement: Arginine Metabolism: Enzymology, Nutrition, and Clinical Significance

Arginine and Cancer¹

Department of Surgery, University of Florida College of Medicine, Surgical Services, North Florida South Georgia VA Health Care System, Gainesville, FL 32608

²To whom correspondence should be addressed. E-mail: lindds{at}surgery.ufl.edu.

Arginine is a dibasic, cationic, semiessential amino acid with numerous roles in cellular metabolism. It serves as an intermediate in the urea cycle and as a precursor for protein, polyamine, creatine and nitric oxide (NO) biosynthesis. Arginine is conditionally essential since it becomes necessary under periods of growth and after recovery after injury. Arginine also promotes wound healing and functions as a secretagogue stimulating the release of growth hormone, insulin-like growth factor 1, insulin, and prolactin. Furthermore, arginine has several immunomodulatory effects such as stimulating T- and natural killer cell activity and influencing pro-inflammatory cytokine levels. The discover that L-arginine is the sole precursor for the multifunctional messenger molecule nitric oxide (NO) led to investigation into the role of arginine in numerous physiologic and pathophysiologic phenomena including cancer. Although NO was first identified in endothelial cells, it is now recognized to be generated by a variety of cell types, including several tumor cell lines and solid human tumors. Unfortunately, the precise role of NO in cancer is poorly understood but it may influence tumor initiation, promotion, and progression, tumor-cell adhesion, apoptosis angiogenesis, differentiation, chemosensitivity, radiosensitivity, and tumor-induced immunosuppression. The biological effects of NO are complex and dependent upon numerous regulatory factors. Further research is necessary to enhance our understanding of the complex mechanisms that regulate NO’s role in tumor biology. A better understanding of the role of arginine-derived NO in cancer may lead to novel antineoplastic and chemopreventative strategies.

KEY WORDS: • arginine • nitric oxide • apoptosis • angiogenesis • cancer

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