PARENTERAL NUTRITION AND MUCOSAL AMINO ACID METABOLISM

肠外营养和粘膜氨基酸代谢

• 批准号: 2674127
• 负责人: PETER J. REEDS
• 金额: $ 5.1万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-18 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2674127
• 关键词: aminoacid metabolism; arginine; cysteine; dietary aminoacid; glutamates; glutathione; glycine; intestinal mucosa; intravenous administration; membrane permeability; nutrition related tag; parenteral feedings; protein biosynthesis; radiotracer; swine; tube feeding

DESCRIPTION: The goal is to quantify the roles of enteral amino acids in intestinal mucosal function, and identify the basis of compromised gut function during parenteral nutrition. Recent isotopic evidence suggests that dietary glutamate is the preferred substrate for mucosal glutathione (GSH) and arginine synthesis. The investigators hypothesize 1: Mucosal GSH and arginine synthesis requires enteral precursors. 2: There is a disproportionate decrease in mucosal GSH and arginine synthesis during TPN. 3: Mucosal GSH and arginine synthesis can be increased by giving enteral supplements of glutamate, glycine and cysteine to animals otherwise maintained by TPN. 4: Omission of these amino acids from enteral feeds will lower mucosal GSH and arginine synthesis but maintain mucosal mass at a higher value than that found in TPN-fed animals. These hypotheses will be tested by achieving the following specific aims: 1: Quantify mucosal GSH and arginine synthesis in animals maintained by enteral elemental diets. 2: Quantify mucosal GSH and arginine synthesis in animals maintained by TPN. 3: Determine whether mucosal GSH and arginine synthesis are increased in animals, maintained by TPN, that are given enteral glutamate, glycine and cysteine. 4: Compare mucosal mass, GSH and arginine synthesis in animals receiving enteral diets that are deficient in glutamate, glycine and cysteine. Multiply-catheterized piglets will receive intravenous or intragastric infusions of [U-13C]glutamate, glutamine and glycine, [2H]-cysteine and [15N]-arginine , to measure the whole body fluxes, portal balances and mucosal uptake of the amino acids. Mass isotopomer distribution analysis of mucosal free and GSH-bound glutamate and mucosal and systemic arginine will be used to identify the source of their precursors. The arginine labeling results will be compared with the mucosal activities of the key enzymes in its synthetic pathway. Identifying the role of specific oral amino acids in mucosal biosynthetic pathways associated with host defenses will aid the development of supplements to help support the nutrient needs and metabolic function of patients receiving TPN.

描述：目标是量化肠道氨基酸在 肠粘膜功能，并找出肠道受损的基础 在肠外营养过程中的作用。最近的同位素证据表明 谷氨酸是粘膜谷胱甘肽的首选底物 (GSH)和精氨酸合成。研究人员假设1：粘膜中的GSH 精氨酸的合成需要肠道前体。他说：有一个 TPN期间粘膜GSH和精氨酸合成不成比例的减少。 3.肠内给药可增加粘膜GSH和精氨酸的合成 谷氨酸、甘氨酸和半胱氨酸对动物的补充 由TPN维护。4：肠道饲料中不含这些氨基酸 会降低粘膜GSH和精氨酸的合成，但维持粘膜质量在 比用TPN喂养的动物的值要高。这些假设将是 通过实现以下具体目标进行测试：1：量化粘膜GSH 和肠道元素饮食维持的动物精氨酸合成。2： 量化全胃肠外营养维持的动物的粘膜谷胱甘肽和精氨酸合成。 3：确定胃黏膜GSH和精氨酸合成是否增加。 由TPN维持的动物，给予肠内谷氨酸、甘氨酸和 半胱氨酸。4：比较动物的粘膜质量、谷胱甘肽和精氨酸合成 接受缺乏谷氨酸、甘氨酸和 半胱氨酸。多管仔猪将接受静脉注射或 [U-13C]谷氨酸、谷氨酰胺和甘氨酸灌胃， [2H]-半胱氨酸和[15N]-精氨酸，测量全身流量，门脉 氨基酸的平衡和粘膜摄取。质量同分异构体 游离谷氨酸和谷胱甘肽结合的谷氨酸和粘膜的分布分析 和全身性精氨酸将被用来确定它们的来源 先驱物。精氨酸标记结果将与粘膜 其合成途径中关键酶的活性。识别 特定的口腔氨基酸在粘膜生物合成途径中的作用 与宿主防御相关的将有助于开发补充剂 帮助支持患者的营养需求和代谢功能 TPN。