The Facts About Protein Our bodies and those of companion animals are orchestrated by cellular machinery, which is directed according to blueprints of DNA. To do so, DNA is transcribed into RNA and then further translated into functional proteins or enzymes. These proteins or enzymes are present in all living cells, are critical for growth and maintenance of the body, and are essential to the well being of both humans and animals. For example, vital body functions, such as blood clotting, fluid balance, visual processes, hormone balance, enzyme activity as well as energy production, all involve proteins or enzymes. Proteins are also important structural constituents of muscle, hair, bone and organs. Our survival relies on constant adjustments to the cellular machinery, which is accomplished by fine-tuning the conversion of DNA into functional proteins. The translation of functional proteins and their ability to perform optimally require a readily available supply of amino acids, which are the building blocks of protein. Although proteins are considered essential for healthy dogs and cats, it is not actually dietary proteins that are utilized by the body, but rather the constituent amino acids, which make up dietary protein. Proteins are made up of hundreds of amino acids. The body utilizes twenty (in dogs) or 21 (in cats) common amino acids in various combinations. While each of these amino acids are important for growth, maintenance and health of the body, some of are considered essential amino acids and others non- essential. Essential amino acids cannot be manufactured by the body from precursors and, therefore, must be provided by the diet. Only ten of the required 20 amino acids are considered essential in dogs, while eleven are essential in cats. Non-essential amino acids are synthesized in the body from precursors and, therefore, need not be present in the diet if adequate amounts of essential amino acids and energy are provided to the animal. Non-essential amino acids are just as vital to the makeup of proteins and crucial for metabolic reactions in the body as essential amino acids. Once dietary protein is consumed, its digestion begins in the stomach where enzymes break down proteins into individual or small groups of amino acids. The amino acids are then absorbed by the intestine and eventually enter the bloodstream to be distributed to the body’s cells and tissues. The fate of absorbed amino acids falls into three general categories: 1) synthesis of tissue protein, 2) manufacture of enzymes, albumin, hormones or other nitrogen-containing compounds and 3) manufacture of energy (or fuel) for the body. Additionally, body proteins are continuously being broken down and new ones manufactured. This process is referred to as protein turnover and is a key physiological process for humans, dogs and cats alike. Protein turnover helps us adapt to our ever-changing environment by maintaining a readily available supply of amino acids necessary to manufacture proteins or enzymes needed at any given time. An optimal level of dietary protein, or rather amino acids, is important in order to maximize the rate of protein turnover, maintain strength and function of skeletal muscle, and support a healthy immune system. Not only is an optimal level of dietary protein important, so is the quality of protein. That is, dietary protein must contain the right balance of amino acids required by the animal and must be highly digestible. Without adequate levels of high quality dietary protein the body compensates by slowing down the rate of protein turnover, thus, decreasing the body’s ability to respond quickly to changes in its environment. For example, to effectively protect and defend the body, the immune system must be able to respond rapidly to potential infections, pathogens and environmental stresses. Amino acids supplied by protein turnover are critical in the manufacture of cells and components of the immune system, such as T-cells and immunoglobulins, respectively. When protein turnover rates are reduced in animals because of low dietary protein intake, the animal is more sensitive to infections and other environmental stresses. Also, without an adequate level of dietary protein to meet the animal’s needs, a protein deficiency may occur. A severe protein deficiency can cause poor food intake, slow growth, weight loss, rough or dull hair coat, or hair loss, impaired immune function and decreased resistance to disease and infection. Chronic, marginal protein deficiency may result in decreased protein reserves, and those animals with inadequate protein reserves may appear healthy but are more susceptible to infectious and cancer causing agents [Allison et al., 1954, McCoy et al., 1956]. A more detailed description of the function of proteins follows. Making up more than 50% of the dry weight of animals, proteins are vital to the proper regulation, function and maintenance of the body. Amino acids absorbed from the gut are rebuilt into new proteins, such as for the: • manufacture of enzymes which are catalysts (e.g., speed up) of all metabolic functions, including energy production, neurological function, immune response and maintenance and health of entire body • manufacture of special blood proteins that serve as carriers for vitamins and minerals and are critical for the general health of animals • manufacture of hormones such as insulin which are necessary to regulate metabolic functions • manufacture of energy (or fuel) for intestinal cells and skeletal muscle. In fact, proteins yield the same amount of usable energy as do carbohydrates • manufacture of structural proteins such as collagen, elastic, keratin, actin and myosin 2 Purina’s Pioneering Research in the Nutritional Management of Canine Food Allergies Introduction It has been estimated that 15% of dogs suffer from allergic diseases [Baker, 1990]. The two most common types of canine allergies are flea allergy dermatitis (or hypersensitivity to fleabites that causes the skin to react via itching and/or the formation of papules) and atopy (allergic reaction against common environmental antigens such as pollen, molds, house dust, mites, etc). Food hypersensitivity (or allergy) ranks third. In fact, it is estimated that food hypersensitivity may be responsible for pruritus (or itching) in up to 62% of dogs presenting with non-seasonal allergic skin disease [Leib and August, 1989]. In addition to causing dermatologic problems in canines, food hypersensitivity may contribute to chronic gastrointestinal diseases [Halliwell and Gorman, 1989]. Specifically, food hypersensitivity appears to be involved in some types of inflammatory bowel disease, which is currently the most common cause of diarrhea and vomiting in dogs [Hall et al., 1989]. What are food allergens? Food consists of a variety of allergenic and nonallergenic components. Food allergens, however, are almost exclusively proteins. Because they are recognized as foreign by the body’s immune system, all dietary proteins have the potential to elicit an allergic response. In fact, most food allergens are very stable molecules that are resistant to food processing, cooking and the digestive process [Taylor, 1992]. Because of this, the specific amino acids sequences that make up the reactive sites (or epitopes) of the allergen are protected. In animals predisposed to food allergy, these reactive sites (or epitopes) are recognized by the immune system as foreign and stimulate the immune system to produce antibodies that target the specific protein. In order for a protein to be considered an allergen, it must be able to stimulate an immune response by the body. The ability to elicit such a response appears to be dependent on the size (also called the molecular weight) and structure of the protein. Most food allergens are reported to be proteins with a molecular weight between 18,000 – 36,000 daltons [Ackerman, 1990]. In soy, for example, the major allergens are reported to be between 20,000 and 78,000 daltons [Awazuhara et al., 1997]. Dietary proteins smaller or larger than 18,000-70,000 daltons size range are not as likely to cause a food allergy because of the physical reactions involved. Potential solutions to food hypersensitivity Companion animals suffering from food hypersensitivity may be managed through nutritional modifications. A major tenant in nutritional management of food hypersensitivity involves the identification and avoidance of the offending antigenic protein. A serious drawback is that the identification of the specific dietary protein responsible for the hypersensitivity requires a substantial commitment by both the 3 veterinarian and pet owner. This approach requires an extensive dietary history on the dog in order to identify all protein sources in the dog’s diet. Then, the dog is fed an elimination diet containing ingredients that have not been previously consumed by the dog. This can be a frustrating experience as it often requires the owner to prepare a homemade diet, often not nutritionally complete and balanced, that contains one protein source and one source of carbohydrate. For up to twelve weeks, this elimination diet must be fed to the dog in order to resolve or reduce the symptoms. If symptoms remain after this period of time, then food hypersensitivity can usually be ruled out. If symptoms are resolved, then food hypersensitivity may be the culprit. In order to confirm the specific offending protein(s), each protein source previously ingested by the dog, must be individually re-introduced into the dog’s diet for a pre-determined time period. If symptoms reappear then the dog likely has a hypersensitivity to that particular protein. After identification of the protein causing the hypersensitivity, the dog is maintained on a diet that is devoid of the offending protein. Until recently, veterinarians managed the food allergic dog by feeding “novel- protein” diets, which are formulated with proteins not normally found in pet foods, such as venison or rabbit meat. These “novel-protein” products should be carefully examined because many commercial diets based on “novel-proteins” may contain other ingredients that contribute significant amounts of non-novel proteins.