ZIEL Research Center of Nutrition and Food Sciences, Abteilung Biochemie, Technische Universität München, Freising, Germany.
Am J Physiol Gastrointest Liver Physiol. 2011 Jul;301(1):G128-37. doi: 10.1152/ajpgi.00017.2011. Epub 2011 Feb 24.
The intestinal peptide transporter PEPT1 mediates the uptake of di- and tripeptides derived from dietary protein breakdown into epithelial cells. Whereas the transporter appears to be essential to compensate for the reduced amino acid delivery in patients with mutations in amino acid transporter genes, such as in cystinuria or Hartnup disease, its physiological role in overall amino acid absorption is still not known. To assess the quantitative importance of PEPT1 in overall amino acid absorption and metabolism, PEPT1-deficient mice were studied by using brush border membrane vesicles, everted gut sacs, and Ussing chambers, as well as by transcriptome and proteome analysis of intestinal tissue samples. Neither gene expression nor proteome profiling nor functional analysis revealed evidence for any compensatory changes in the levels and/or function of transporters for free amino acids in the intestine. However, most plasma amino acid levels were increased in Pept1(-/-) compared with Pept1(+/+) animals, suggesting that amino acid handling is altered. Plasma appearance rates of (15)N-labeled amino acids determined after intragastric administration of a low dose of protein remained unchanged, whereas administration of a large protein load via gavage revealed marked differences in plasma appearance of selected amino acids. PEPT1 seems, therefore, important for overall amino acid absorption only after high dietary protein intake when amino acid transport processes are saturated and PEPT1 can provide additional absorption capacity. Since renal amino acid excretion remained unchanged, elevated basal concentrations of plasma amino acids in PEPT1-deficient animals seem to arise mainly from alterations in hepatic amino acid metabolism.
肠肽转运蛋白 PEPT1 介导源自膳食蛋白质分解的二肽和三肽进入上皮细胞。虽然该转运蛋白似乎对于补偿氨基酸转运蛋白基因突变患者（如胱氨酸尿症或 Hartnup 病）氨基酸输送减少至关重要，但它在整体氨基酸吸收中的生理作用仍不清楚。为了评估 PEPT1 在整体氨基酸吸收和代谢中的定量重要性，使用刷状缘膜囊泡、外翻肠囊和 Ussing 室以及对肠组织样本进行转录组和蛋白质组分析，研究了 PEPT1 缺陷型小鼠。基因表达、蛋白质组谱分析或功能分析均未显示出肠道中游离氨基酸转运体水平和/或功能发生任何代偿性变化的证据。然而，与 Pept1(+/+)动物相比，Pept1(-/-)小鼠的大多数血浆氨基酸水平升高，表明氨基酸处理发生改变。胃内给予低剂量蛋白质后，（15）N 标记氨基酸的血浆出现率保持不变，而经胃管给予大量蛋白质负荷时，选定氨基酸的血浆出现率存在明显差异。因此，PEPT1 似乎仅在高膳食蛋白质摄入后对整体氨基酸吸收很重要，此时氨基酸转运过程饱和，PEPT1 可以提供额外的吸收能力。由于肾氨基酸排泄保持不变，PEPT1 缺陷型动物基础血浆氨基酸浓度升高似乎主要源于肝氨基酸代谢的改变。
