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==1. What is Arginine?==

==What is Arginine?==

Arginine is an '''essential amino acid''' for dogs and cats. It is classified as a '''gluconeogenic''' amino acid and contains a positively charged nitrogen side chain that can be used as a binding site for other molecules. Dietary arginine is absorbed by a dibasic amino acid transporter in the small intestine (particularly the jejunum) and plasma arginine is actively reabsorbed in the proximal tubule of the kidney. Species that do not require dietary arginine (such as humans) are able to endogenously synthesise adequate amounts of this amino acid through the conversion of glutamate into ornithine; ornithine is ultimately converted into arginine in the urea cycle through the activity of pyrroline-5-carboxylate synthase and ornithine aminotransferase. Low activity of these enzymes are found in dogs and cats<ref name="Burns">Burns RA, et al.  Arginine: An Indispensable Amino Acid for Mature Dogs. J Nutr 1981; 111:1020-1024.</ref><ref name="Morris">Morris JG. Nutritional and Metabolic Responses to Arginine Deficiency in Carnivores J Nutr 1985;115:524-531.</ref>. '''Dogs and cats have an absolute requirement for dietary arginine'''.

Arginine is an '''essential amino acid''' for dogs and cats. It is classified as a '''gluconeogenic''' amino acid and contains a positively charged nitrogen side chain that can be used as a binding site for other molecules. Dietary arginine is absorbed by a dibasic amino acid transporter in the small intestine (particularly the jejunum) and plasma arginine is actively reabsorbed in the proximal tubule of the kidney. Species that do not require dietary arginine (such as humans) are able to endogenously synthesise adequate amounts of this amino acid through the conversion of glutamate into ornithine; ornithine is ultimately converted into arginine in the urea cycle through the activity of pyrroline-5-carboxylate synthase and ornithine aminotransferase. Low activity of these enzymes are found in dogs and cats<ref name="Burns">Burns RA, et al.  Arginine: An Indispensable Amino Acid for Mature Dogs. J Nutr 1981; 111:1020-1024.</ref><ref name="Morris">Morris JG. Nutritional and Metabolic Responses to Arginine Deficiency in Carnivores J Nutr 1985;115:524-531.</ref>. '''Dogs and cats have an absolute requirement for dietary arginine'''.

==2. Why is it Important?==

==Why is it Important?==

Arginine plays a critical role in the detoxification of ammonia, resulting from the turnover and breakdown of proteins. It is an important intermediate in the urea cycle which converts ammonia to urea. <span style="color:red">In cats the arginine dietary protein in order to handle the increased need for detoxifying ammonia released from amino acid catabolism a<ref name="Taylor">Taylor TP, et al. Increasing dispensable amino acids in diets of kittens fed essential amino acids at or below their requirement increases the requirement for arginine. Amino Acid 1997;13:257-272.</ref><SENTENCE NEEDS REVIEW</span>. Cats are also highly sensitive to dietary arginine deficiency, feeding an arginine free diet to cats can result in hyperammonemia and death within a few hours<ref>Morris JG and Rogers QR. Ammonia intoxication in the near-adult cat as a result of a dietary deficiency of arginine. Science 1978 Jan 27;199(4327):431-2</ref>.

Arginine plays a critical role in the detoxification of ammonia, resulting from the turnover and breakdown of proteins. It is an important intermediate in the urea cycle which converts ammonia to urea. <span style="color:red">In cats the arginine dietary protein in order to handle the increased need for detoxifying ammonia released from amino acid catabolism a<ref name="Taylor">Taylor TP, et al. Increasing dispensable amino acids in diets of kittens fed essential amino acids at or below their requirement increases the requirement for arginine. Amino Acid 1997;13:257-272.</ref><SENTENCE NEEDS REVIEW</span>. Cats are also highly sensitive to dietary arginine deficiency, feeding an arginine free diet to cats can result in hyperammonemia and death within a few hours<ref>Morris JG and Rogers QR. Ammonia intoxication in the near-adult cat as a result of a dietary deficiency of arginine. Science 1978 Jan 27;199(4327):431-2</ref>.

==3. Roles in the Body==

==Roles in the Body==

Arginine is a structural component of proteins; serves as a key substrate for the detoxification of ammonia; stimulates the release of hormones, such as insulin, glucagon, and gastrin; and is a precursor to nitric oxide (NO), which is used as a cell signalling mediator<ref>National Research Council (NRC). Protein and Amino Acids. In Nutrient Requirements for Dogs and Cats. 2006 Washington, DC: National Academies Press p. 120-122.</ref>.

Arginine is a structural component of proteins; serves as a key substrate for the detoxification of ammonia; stimulates the release of hormones, such as insulin, glucagon, and gastrin; and is a precursor to nitric oxide (NO), which is used as a cell signalling mediator<ref>National Research Council (NRC). Protein and Amino Acids. In Nutrient Requirements for Dogs and Cats. 2006 Washington, DC: National Academies Press p. 120-122.</ref>.

==4. Consequences of Arginine Deficiency==

==Consequences of Arginine Deficiency==

===Dogs:===

===Dogs:===

Feeding of an arginine deficient diet to kittens results in diarrhoea, weight loss, food refusal, ataxia, hyperammonemia, and urinary orotic aciduria<ref name="Morris"/>. Feeding a diet that has no arginine but contains substantial levels of other amino acids can result in death within a few hours<ref name="Taylor"/>.

Feeding of an arginine deficient diet to kittens results in diarrhoea, weight loss, food refusal, ataxia, hyperammonemia, and urinary orotic aciduria<ref name="Morris"/>. Feeding a diet that has no arginine but contains substantial levels of other amino acids can result in death within a few hours<ref name="Taylor"/>.

==5. Toxicity==

==Toxicity==

There are no studies on either acute or chronic toxicity related to feeding high doses of arginine to dogs and no reports of safe upper limits. Kittens fed purified diets containing arginine at 5-10 times above the requirement had a decrease in growth rate<ref>Taylor TP, et al. Optimizing the pattern of essential amino acids as the sole source of dietary nitrogen supports near maximal growth in kittens. J Nutr 1996;126:2243-2252.</ref>, but immediate adverse effects were not noted. Toxicity studies in adult cats are lacking.

There are no studies on either acute or chronic toxicity related to feeding high doses of arginine to dogs and no reports of safe upper limits. Kittens fed purified diets containing arginine at 5-10 times above the requirement had a decrease in growth rate<ref>Taylor TP, et al. Optimizing the pattern of essential amino acids as the sole source of dietary nitrogen supports near maximal growth in kittens. J Nutr 1996;126:2243-2252.</ref>, but immediate adverse effects were not noted. Toxicity studies in adult cats are lacking.

==6. Dietary Sources==

==Dietary Sources==

Sufficient arginine is found in plant and animal protein sources, such as muscle meat, eggs, dairy protein (i.e., casein), cereal grains, and pulses (i.e., legumes).

Sufficient arginine is found in plant and animal protein sources, such as muscle meat, eggs, dairy protein (i.e., casein), cereal grains, and pulses (i.e., legumes).

==7. Diagnosing Arginine Deficiency==

==Diagnosing Arginine Deficiency==

Diagnosis of arginine deficiency is based on fasting plasma amino acid levels and the presence of urinary orotic acid.

Diagnosis of arginine deficiency is based on fasting plasma amino acid levels and the presence of urinary orotic acid.

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