Arginine
Arginine, 2-amino-5-guanidinovaleric acid, is a basic amino acid with a positively charged guanidinium group. Arginine is considered to be a semi-essential amino acid. It can be synthesized in animal tissues at a rate sufficient for maintenance in the adult but not rapidly enough to support growth in the young animal. It is thus an essential amino acid for growth but not for maintenance. In the mammalian body, arginine takes part in the formation of urea yielding ornithine. Arginine may be synthesized in the mammalian body from alpha-ketoglutaric acid, glutamic acid or proline. While arginine can be synthesized by these mammals, it cannot be synthesized at a rate sufficient to meet the demands of normal growth. L-arginine is the precursor amino acid critical to the synthesis of nitric oxide by nitric oxide synthase (cNOS or eNOS), the enzyme responsible for constitutive production of nitric oxide (NO) by vascular endothelial and neural cells. The L-arginine acts to prolong vasodilatation by inducement of the nitric-oxide synthase pathway. The L-arginine also acts to induce vascular neogenesis through action of endothelial growth factor (EGF) and it acts to induce sensory neogenesis through action of nerve growth factor (NGF). Nitric oxide (NO) has many beneficial effects, including vasodilation and inhibiting smooth muscle cell hyperproliferation. However, the temporal, optical and hydrolytic instability of nitric oxide donor moieties has rendered them inefficient for use in reducing restenosis. Nitric oxide is synthesized from L-arginine, or its polymeric and/or oligomeric derivatives, by the enzyme nitric oxide synthase, a homodimeric flavo-hemoprotein that catalyzes the 5-electron oxidation of L-arginine to produce NO and L-citrulline. L-Arginine is desirable for stimulating the immune system and assisting in the utilization of other amino acids. L-arginine has several other advantages, including blocking the formation of tumors, causing release of
growth hormone, forming citrulline and ornithine by hydrolysis, detoxification of ammonia, assisting in liver regeneration, wound healing, growth and sperm formation, and lowering cholesterol. Among other therapeutic properties, nitric oxide relaxes vascular smooth muscle cells and inhibits the cells' proliferation. Inhibition of proliferation of vascular smooth muscle cells is believed to contribute to the reduction or elimination of restenosis.
L-arginine is an amino acid that can be loaded to a higher total effective dose of Nitric oxide than a conventional Nitric oxide donor. One of the advantages of using L-arginine as an NO donor is that the rate of Nitric oxide release from L-arginine is controlled and sustained, which is an improvement over using conventional NO donors. In addition, several molecular components are required in the biosynthesis of nitric oxide from L-arginine including the enzymes iNOS and eNOS, with L-arginine often being the limiting reagent in this reaction scheme. When L-arginine is absorbed by a cell in the presence of eNOS, nitric oxide is produced. Arginine has a special role in the physiology of mammals. The main pathway for elimination of excess nitrogen is the urea cycle, whereby liver cells use a set of enzymes which turn arginine into ornithine, ornithine into citrulline, and citrulline back into arginine with the net effect of releasing nitrogen from ammonia (which is produced by ultimate degradation of amino acids) as a constituent of urea. The synthetic pathway for arginine commences with ornithine. Ornithine is combined with carbamyl phosphate to produce citrulline, which in turn is combined with aspartate, in the presence of adenosine triphosphate (ATP), to produce argininosuccinate. In the final step, fumarate is split from argininosuccinate, to produce arginine. The degradative pathway for arginine is by the hydrolytic action of arginase, to produce ornithine and urea. All of the reactions described above form the urea cycle. Arginine's best-studied functions are in the urea cycle and as an essential amino acid for the synthesis of proteins. However, other functions for arginine have been found. L-arginine is a precursor to the natural endogenous analgesic substance, kyotorphin. L-arginine can be used in the treatment of a number of high vascular resistance disorders including hypertension, primary or secondary vasospasm, angina pectoris, cerebral ischemia and preeclampsia of pregnancy (toxemia).
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