Amino acid metabolism in parenterally and enterally fed piglets : how important is gut metabolism?
The small intestine has generally been viewed as a digestive organ responsible for the absorption of dietary nutrients for delivery to other organs for metabolism. However, the small intestine is also a metabolic organ responsible for the synthesis, interconversion and catabolism of several amino acids. Therefore, this thesis investigated the role of the neonatal small intestine in the metabolism of the urea cycle amino acids. The first study found that dietary glutamate may replace glutamine as a primary fuel for the small intestine because no benefit to gut growth or nitrogen retention was observed from feeding a glutamine-rich diet. Subsequently, when piglets were fed identical diets via the vena cava, portal vein or stomach, overall metabolic responses to route of feeding suggested that small intestinal atrophy affects nitrogen metabolism to a greater extent than liver bypass. Furthermore, analyses of amino acid pools in the plasma, liver, small intestinal mucosa and kidney revealed that dramatic alterations in P5C amino acid metabolism were effected by feeding via different routes. The role of the neonatal small intestine in arginine synthesis from proline was then investigated. Arginine deficiency-induced hyperammonemia was exacerbated by the removal of dietary proline in orally fed piglets only; parenterally fed piglets experienced severe hyperammonemia whether or not proline was present. Thus, de novo arginine synthesis is inadequate in the piglet and proline can be converted to arginine only when gut metabolism is maintained. To quantify the interconversions between arginine and profine, kinetic analysis was used in fed piglets because the fasting state was found to be unsuitable for kinetic analysis of amino acids. Bolus infusion experiments were first conducted to determine pool size, half-life and primed to constant dose ratio for the constant infusion experiment. The constant infusion of amino acid tracers via the portal vein or stomach demonstrated that arginine and ornithine syntheses from proline were completely dependent on gut first pass metabolism because the enzyme ornithine aminotransferase is localized to the gut. Therefore, the small intestine is an important metabolic organ in the neonate and its role in amino acid metabolism is essential to whole body homeostasis.