Arginine, a semi-essential amino acid, is involved in numerous areas of human biochemistry, including ammonia detoxification, hormone secretion, and immune modulation. Arginine is also well known as a precursor to nitric oxide (NO), a key component of endothelial-derived relaxing factor, an endogenous messenger molecule involved in a variety of endothelium-dependent physiological effects in the cardiovascular system. Because of arginine's NO-stimulating effects, it can be utilized in therapeutic regimens for angina pectoris, congestive heart failure, hypertension, coronary heart disease, preeclampsia, intermittent claudication, and erectile dysfunction. In addition, arginine has been studied in the treatment of HIV/AIDS, athletic performance, burns and trauma, cancer, diabetes and syndrome X, gastrointestinal diseases, male and female infertility, interstitial cystitis, immunomodulation, and senile dementia. Toxicity, dosage considerations, and contraindications are also reviewed.
(Altern Med Rev 2002;7(6):512-522)
Arginine is a semi-essential amino acid involved in multiple areas of human physiology and metabolism. It is not considered essential because humans can synthesize it de novo from glutamine, glutamate, and proline. However, dietary intake remains the primary determinant of plasma arginine levels, since the rate of arginine biosynthesis does not increase to compensate for depletion or inadequate supply. (1,2)
Arginine contains four nitrogen atoms per molecule, making it the most abundant nitrogen carrier in humans and animals (Figure 1). Although it is not a major inter-organ shuttle of nitrogen, arginine nevertheless plays an important role in nitrogen metabolism as an intermediate in the urea cycle, making it essential for ammonia detoxification. (3)
Arginine is synthesized in mammals from glutamine via pyrroline 5-carboxylate (P5C) synthetase and proline oxidase in a multi-step metabolic conversion. (4) In adults, most endogenous arginine is derived from citrulline, a by-product of glutamine metabolism in the gut or liver. Citrulline is released into the circulation and taken up primarily by the kidney for conversion into arginine. (5)
Supplemental arginine in enteral feeding is readily absorbed (6) About half of ingested arginine is rapidly converted in the body to ornithine, primarily by the enzyme arginase. (7) Ornithine, in turn, can be metabolized to glutamate and proline, or through the enzyme ornithine decarboxylase into the polyamine pathway for degradation into compounds such as putrescine and other polyamines.
In addition to the above-mentioned metabolic activity, arginine is a precursor for the synthesis of proteins, as well as nitric oxide, urea, creatine, and agmatine. (8) Arginine that is not metabolized by arginase to ornithine is processed by one of four other enzymes: nitric oxide synthase (to become nitric oxide); arginine:glycine amidinotransferase (to become creatine); arginine decarboxylase (to become agmatine); or arginyl-tRNA synthetase (to become arginyl-tRNA, a precursor to protein synthesis). Arginine is also an allosteric activator of N-acetylglutamate synthase, which synthesizes N-acetylglutamate from glutamate and acetyl-CoA. (9)
Mechanisms of Action
Arginine has significant effects on endocrine function--particularly adrenal and pituitary secretion--in humans and animals. Arginine administration has long been known to stimulate the release of catecholamines, (10) insulin and glucagon, (11) prolactin, (12) and growth hormone (GH). (13,14) Little is known, however, about the exact mechanism by...
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