Metabolic fate of amino acids in the gut of the postnatal developing pig

全体氮(N)利用效率在哺乳期较高，在断奶过渡期和生长-肥育期较低。然而，在组织器官、细胞和分子水平上，与出生后全身氮利用效率下降相关的机制和因素并不十分清楚。肠道具有代谢活性，肠内和动脉来源的氨基酸（AA）被肠道广泛利用，以各种氮化合物的形式在肠道内进行微生物分解代谢和生长、粘膜细胞分解代谢和生长以及胃肠道代谢内源性损失。氨基酸转运体是引导AA在器官和组织之间流动的通道，在全身水平上受到高度调节和协调。我的NSERC Discovery研究项目的长期目标是确定和理解与猪全身氮利用效率下降（重点是肠道）有关的AA利用和代谢主要途径的产后变化相关的因素和机制。我未来五年的具体目标是：(1)研究出生后肠道微生物分解代谢和生长对AA利用的变化；ii)检查出生后顶端、线粒体内膜的细胞和分子变化，以及中性（如谷氨酰胺、亮氨酸和甘氨酸）和酸性AA（如小肠中的谷氨酸）的基底外侧运输；iii)研究出生后AA分解代谢的变化及其对细胞谷胱甘肽、蛋白质、RNA和DNA生物合成的利用。综合研究工具将用于揭示产后规划和饮食类型的变化如何导致肠道对AA的总体利用增强和全身氮利用效率降低。本研究将提高我们在基础胃肠生理学和蛋白质营养与代谢方面的知识，培养高素质的人才，为提高仔猪生长和猪饲粮氮利用效率提供营养和生物技术策略。

Efficiency of whole-body nitrogen (N) utilization for growth is high during the suckling and becomes low during the weaning transition and growing-finishing phases in pigs. However, mechanisms and factors associated with the postnatal decreases in whole-body efficiency of N utilization are not very clear at the tissue-organ, cellular and molecular levels. The intestine is metabolic active and both enteral and arterial sources of amino acids (AA) are extensively utilized by the intestine for microbial catabolism and growth in the lumen, mucosal cellular catabolism and growth and the gastrointestinal metabolic endogenous losses as various nitrogenous compounds. Amino acid transporters are gateways in directing the AA fluxes across organs and tissues and these are highly regulated and coordinated at the whole body level. The long-term goal of my NSERC Discovery research program is to identify factors and to understand mechanisms that are associated with postnatal changes of the major pathways of AA utilization and metabolism responsible for the declining efficiency of the whole-body N utilization with emphasis on the gut in the pig. My specific objectives for the next five years are i) to investigate postnatal changes of AA utilization for microbial catabolism and growth in the lumen; ii) to examine cellular and molecular aspects of postnatal changes in the apical, mitochondrial inner membrane, and basolateral transport of neutral, e.g., glutamine, leucine and glycine, and acidic AA, e.g., glutamate in the small intestine; and iii) to study postnatal changes of AA catabolism and utilization for biosyntheses of cellular glutathione, proteins, RNA and DNA. Integrated research tools will be used to reveal how postnatal programming and changes of dietary types are responsible for an overall enhanced gut utilization of AA and the reduced efficiency of whole-body N utilization. The proposed research will improve our knowledge in basic gastrointestinal physiology and protein nutrition and metabolism and train highly qualified personnel, leading to nutritional and biotechnological strategies for improving neonate growth and the efficiency of N utilization in pig feeding.