The objectives of this project are to study amino acid transport and metabolism, fatty acid metabolism, their relationships to gluconegenesis and ketogenesis, and their metabolic control. We will use the sheep as the basic animal model to continue our broad and long-standing studies on ruminant and comparative metabolism. Adult ruminants normally absorb little or no glucose since the rumen ferments dietary carbohydrates to volatile fatty acids. Further, ketone bodies are produced by the rumen epithelium. A unique site of ketogenesis thus is present in ruminants and they must rely upon gluconeogenesis for nearly all of their metabolic glucose needs. Acidosis and also hypoglycemia together with hypoaminoacidemia and ketosis is a common problem during pregnancy and lactation. It thus is believed that the ruminant is an excellent animal model for a variety of metabolic studies. In addition, this study should aid in clarifying the basic metabolic adaptations the body undergoes in adapting to starvation, pregnancy, parturition and lactation. In this project, the metabolism and unidirectional fluxes of branched-chain amino acids, glycine-serine, and other amino acids are being stressed since they are important in N transport between various tissues of the body. They also are important under conditions of trauma, muscle wasting diseases, and chronic renal failure. The metabolism and recycling of ketogenic and glucogenic substrates (such as propionate) through ketone bodies and glucose, respectively, will be investigated. A deal of emphasis is being placed on measuring venoarterial concentration and 14C differences and rates of blood flow across the brain, liver, kidneys, gut and lower extremities (muscle). The simultaneous uptake and release of metabolites and their interconversions thus are measured and compared with the turnover in the whole body. The effects of feeding, acidosis, various hormonal perturbations, starvation, pregnancy and lactation are being investigated.