Under normal circumstances in humans 30% or more of the urea produced by the liver is not excreted in urine but is hydrolyzed by gut bacteria; a considerable portion of the resulting nitrogen (N) returned to the host as ammonia is incorporated into amino acids and proteins. The difference between urea production and excretion rates is termed urea N recycling. Since urinary urea is the major form by which N is released from the body, this process of recovering and recycling urea N makes a significant contribution toward the status of whole body N balance. Urea N recycling is altered in various physiologic states and varies with dietary protein intake in normal subjects. Urea N recycling has not thus far been examined in the protein catabolic state associated with cancer cachexia, a condition characterized by progressive muscle protein loss resulting from altered protein metabolism, chronic protein-calorie malnutrition and negative N balance. The changes in protein metabolism associated with cachexia are similar to those induced by sepsis in which urea N recycling appears to be absent; we therefore expect urea N recycling to be severely diminished in cachexia. A relative inability to recover and reutilize urea N, although not a direct cause of cachexia, would nonetheless contribute to negative N balance. We will compare the process of urea N recycling in cachectic cancer patients to normal subjects on high and low protein diets and in the presence of a glucose infusion which exhibits a nitrogen-sparing effect in normal subjects but not in cachectic patients. Non-cachectic cancer patients and anorectic subjects without cancer will also be studied to determine whether alterations in urea N metabolism result from the cancer itself or are secondary to malnutrition. Despite the potential significance of urea N recycling for overall N economy, there is almost no quantitative information regarding the distribution of recycled N between urea and various amino acids. We will for the first time quantify the incorporation of orally administered 15N- ammonia (the form in which urea recycles from the gut) into multiple plasma amino acids and urea to quantify this distribution pattern as a function of dietary protein and glucose infusion in all groups of subjects. Since cachectic subjects generally exhibit anorexia and malnutrition, it is imperative that nutritional support should have the requisite precursors to assist the urea N recycling process to recover and reutilize N which would otherwise be lost from the body. The knowledge gained from these studies will provide information which can ultimately aid in the formulation of nutritional therapies which will facilitate the recovery and reutilization of urea N in cachectic subjects and thereby improve their N metabolic economy.
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