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

猪的氮素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，与出生后氮利用效率降低相关的机制和因素还不是很清楚。肠是代谢活性的，并且肠内和动脉来源的氨基酸（AA）被肠广泛用于管腔中的微生物催化和生长、粘膜细胞催化和生长以及胃肠道代谢内源性损失（作为各种含氮化合物）。氨基酸转运蛋白是引导AA通量穿过器官和组织的门户，并且这些在全身水平上受到高度调节和协调。我的NSERC发现研究计划的长期目标是确定因素，并了解与AA利用和代谢的主要途径的出生后变化相关的机制，这些变化导致猪全身N利用效率下降，重点是肠道。我在未来五年的具体目标是：i）研究AA利用率在出生后的变化，以促进微生物的代谢和管腔中的生长; ii）研究出生后在顶端、线粒体内膜和基底侧中性转运中的细胞和分子方面的变化，例如，谷氨酰胺、亮氨酸和甘氨酸，以及酸性AA，例如，iii）研究生后AA催化剂的变化以及对细胞谷胱甘肽、蛋白质、RNA和DNA的生物合成的利用。综合研究工具将被用来揭示如何出生后编程和饮食类型的变化是负责整体增强肠道利用AA和降低效率的全身N利用。拟议的研究将提高我们在基础胃肠道生理学和蛋白质营养和代谢方面的知识，培养高素质的人才，从而制定营养和生物技术策略，以改善新生儿的生长和猪饲养中氮的利用效率。

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.