Answer to Biochemistry Question AM-05
Structure of arginine
Arginine is for humans a conditional essential amino acid, since we can synthesize, but it may not be enough for our requirements, depending of the health status and the stage of development. For infants, arginine is nutritionally essential, and in adults some must still be consumed through diet, especially in some conditions as trauma, burn injury, small-bowel resection and renal failure.
Arginine is synthesized from citrulline. Citrulline is formed mainly in the small intestine and is recovered from circulation by the kidney, that converts most of it in arginine (it explains the increased requirement of arginine in patients with renal failure of small-bowel resection).
Not only the kidney and the liver, where Urea Cycle occurs, can produce arginine. In fact, several tissues can synthesize, in lower quantities, this amino acid, since it can yield important biologically active compounds.
As mentioned before, an important source of arginine is the diet. Arginine is found in a variety of foods including meats, dairy products and seafood. It appears also in vegetarian food as wheat germ, nuts, seeds, soybeans and others. Some energy drinks and body builder supplements are enriched with arginine.
Arginine, as stated in the question, is the precursor of Nitric Oxide and Urea.
The synthesis of Nitric Oxide occurs in a two steps reaction catalyzed by Nitric Oxide Synthase (NOS) that produces NwHydroxy-L Arginine (NOHLA) as an intermediary:
L-Arg + NADPH.H+ + O2 à [Nw-hydroxy-Larginine] + NADP+ +H2O
[Nw-hydroxy-Larginine] + NADPH.H+ + O2 à citrulline + NO + NADP+
Nitric oxide synthase contains as cofactors FMN, FAD, tetrahydrobiopterin and Fe+++ Hem. There are three isoforms of this enzyme and it is present in many tissues and cell types: neurons, macrophages, hepatocytes, myocytes of smooth muscle, endothelial cells of the blood vessels and epithelial cells of the kidneys.
The synthesis of urea from arginine occurs in the last reaction of the Urea Cycle:
L-Arg + H2O —-à ornithine + Urea
This reaction is catalyzed by Arginase, an enzyme with two isoforms: Arginase I, expressed in the cytoplasm of the liver, and related to Urea Cycle, and Arginase II, that appears in several tissues and apparently act, as a competing enzyme for the same substrate, like some kind of regulator of the arginine available for the action of Nitric Oxide Synthase.
Besides the importance of Arginine as a precursor of Nitric Oxide and Urea, and its obvious role as one of the 20 amino acids that constitute the “building blocks” of proteins, Arginine is also precursor of Creatine, and can be interconverted with other amino acids as proline and glutamate. Arginine also can yield other nitrogenated compounds, depending on the specific tissue.
More information about Arginine and Arginine metabolism in:
Morris, S.M. JR.: Arginine, Beyond Protein, Amer J Clin Nutr 83(2) 508S-512S, 2006
Good graphics about Urea synthesis in:
For the uses of Arginine based on scientific evidence: