Grant: Discovery Grants Program - Individual

LONG TERM OBJECTIVE: Many essential amino acids are used for non-protein functions that can consume a substantial amount of dietary amino acids. My long term objective is to quantify the impact of these maintenance functions and optimize diets by improving amino acid utilization for growth in young animals. In particular, this Discovery Grant will focus on the non-protein roles of arginine and methionine, as precursors for creatine synthesis in young pigs. BACKGROUND: In young pigs, both arginine and methionine are essential amino acids, and both have several important metabolic roles other than protein synthesis. For example, both amino acids are necessary for creatine synthesis which is very demanding in young growing pigs. Arginine is converted to guanidinoacetic acid (GAA) in the kidney and then methylated by methionine to form creatine in the liver. We have shown that when dietary arginine or methionine is limiting, creatine synthesis is particularly impaired. Creatine serves as a key energy buffer in animals and is known to promote growth and cognitive performance. In growing animals, the demand for creatine cannot be met by this de novo synthesis and must be consumed. Creatine and GAA can potentially be very effective as growth-promoting feed supplements, especially in creatine-free all-grain diets. Their use in the swine industry has enormous potential as supplements in young pigs, given the essentiality of arginine early in life and their potential for improved growth and health. In this respect, the potential of creatine and GAA as supplements in young pig diets warrants further research and the mechanism of sparing essential amino acids needs to be better understood. SPECIFIC OBJECTIVES: Overall, we want to understand how creatine synthesis affects arginine and methionine requirements in young growing pigs. Using our well established surgically altered piglet model, we will use isotope kinetics to determine: 1a) How much dietary arginine is required to synthesize creatine; 1b) How much arginine and methionine are spared if creatine or GAA is supplemented; 2a) How is the absorbed creatine and GAA used by tissues; 2b) Is citrulline a better precursor than arginine for creatine synthesis; 3a) How bioavailable are creatine and GAA supplements: 3b) How much extra methionine is required to facilitate creatine synthesis from GAA supplements. IMPACT: This research will: 1) enhance understanding of the metabolic fate of essential amino acids to more precisely design amino acid supply to young pigs and reduce environmental waste; 2) characterize the benefits of creatine and GAA as supplements in swine production; 3) further train exceptional HQP. This program is well suited for training of HQP (15 directly funded over next 5 years) with mechanistic and applied questions, sophisticated techniques, and presentation opportunities that will augment their graduate skills and prepare them to contribute to the broader Canadian community.