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PEPTIDE ASSIMILATION IN MALNUTRITION AND MALABSORPTION

营养不良和吸收不良中的肽同化

基本信息

批准号：
3150980
负责人：
SIAMAK A ADIBI
金额：
$ 12.36万
依托单位：
MONTEFIORE UNIVERSITY HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
1978
资助国家：
美国
起止时间：
1978-06-15 至 1986-11-30
项目状态：
已结题

项目摘要

Previous studies have shown that dipeptides, when introduced into the lumen of human intestine are taken up intact by a peptide transport system, and are partly hydrolyzed to amino acids by brush-border membrane enzymes. The positioning of glycine in the N-terminal position appears to increase the opportunity for intact transport of dipeptides at the expense of reducing brush-border membrane hydrolysis. In a preliminary study, we have compared absorption rates of amino acids from a mixture of dipeptides and a corresponding amino acid mixture. The dipeptide mixture consisted of a series of dipeptides all having glycine in the N-terminal position and either an essential or non-essential amino acid in the C-terminal position. These results have shown: a) the rates of amino acid absorption are considerably greater from the dipeptide than amino acid mixtures, and b) the competition for absorption is minimized or abolished when amino acids are presented in dipeptide rather than in free form. We believe these findings may have useful clinical application in the practice of enteral nutrition, which currently utilizes either amino acid mixtures or protein hydrolysates as the source of nitrogen. We believe a dipeptide mixture may be superior to either free amino acids or protein hydrolysates. To investigate our hypothesis, we have proposed a series of experiments to determine the efficacy of absorption from the dipeptide mixture in the conditions which usually may require enteral nutrition therapy, such as short bowel syndrome, intestinal disease, pancreatic insufficiency, and malnutrition. In view of the fact that very little information is available on the kinetics of peptide absorption or hydrolysis in conditions of malnutrition and intestinal disease in man, we have designed a series of experiments to investigate this problem. Finally, a series of experiments is designed to investigate parameters of nutrition and metabolism and parameters of intestinal morphology, composition, metabolism, and function when a dipeptide mixture replaces an amino acid mixture as the source of nitrogen for enteral nutrition.

以前的研究表明，二肽，当引入到管腔，被肽转运系统完整吸收，被刷状缘膜酶部分水解成氨基酸。的甘氨酸在N-末端位置的定位似乎增加了二肽的完整运输的机会，以减少刷状缘膜水解在初步研究中，我们比较了氨基酸的吸收速率从二肽和相应的氨基酸混合物。二肽混合物由以下组成：一系列二肽，在N-末端位置均具有甘氨酸， C-末端的必需或非必需氨基酸位置这些结果表明：a）氨基酸吸收速率来自二肽的比来自氨基酸混合物的大得多，并且 B）当氨基取代时，酸以二肽而不是游离形式存在。我们认为这些发现可能在实践中具有有用的临床应用，肠内营养，目前利用氨基酸混合物或蛋白质水解产物作为氮源。我们认为一种二肽混合物可能上级游离氨基酸或蛋白质水解产物。为了研究我们的假设，我们提出了一系列确定从二肽吸收的功效的实验在通常需要肠内营养的条件下，治疗，如短肠综合征，肠道疾病，胰腺营养不足和营养不良。鉴于很少有关于肽吸收的动力学的信息是可获得的，或者在人类营养不良和肠道疾病条件下水解，设计了一系列实验来研究这个问题。最后，设计了一系列的实验来研究营养和代谢以及肠形态学参数，当二肽混合物替代多肽时，氨基酸混合物作为肠内营养的氮源。