Daniel Hannelore
Molecular Nutrition Unit, Technical University of Munich, D-85350 Freising-Weihenstephan, Germany.
Annu Rev Physiol. 2004;66:361-84. doi: 10.1146/annurev.physiol.66.032102.144149.
Intestinal protein digestion generates a huge variety and quantity of short chain peptides that are absorbed into intestinal epithelial cells by the PEPT1 transporter in the apical membrane of enterocytes. PEPT1 operates as an electrogenic proton/peptide symporter with the ability to transport essentially every possible di- and tripeptide. Transport is enantio-selective and involves a variable proton-to-substrate stoichiometry for uptake of neutral and mono- or polyvalently charged peptides. Neither free amino acids nor peptides containing four or more amino acids are accepted as substrates. The structural similarity of a variety of drugs with the basic structure of di- or tripeptides explains the transport of aminocephalosporins and aminopenicillins, selected angiotensin-converting inhibitors, and amino acid-conjugated nucleoside-based antiviral agents by PEPT1. The high transport capacity of PEPT1 allows fast and efficient intestinal uptake of the drugs but also of amino acid nitrogen even in states of impaired mucosal functions. Transcriptional and post-transcriptional regulation of PEPT1 occurs in response to alterations in the nutritional status and in disease states, suggesting a prime role of this transporter in amino acid absorption.
肠道蛋白质消化会产生种类繁多、数量巨大的短链肽,这些短链肽通过肠上皮细胞顶端膜上的肽转运体1(PEPT1)被吸收进入肠道上皮细胞。PEPT1作为一种生电质子/肽同向转运体,能够转运几乎所有可能的二肽和三肽。转运具有对映体选择性,对于中性及单价或多价带电肽的摄取,质子与底物的化学计量比各不相同。游离氨基酸以及含有四个或更多氨基酸的肽均不被视为底物。多种药物与二肽或三肽基本结构的结构相似性,解释了氨基头孢菌素、氨基青霉素、某些血管紧张素转换酶抑制剂以及氨基酸共轭核苷类抗病毒药物可通过PEPT1进行转运的现象。PEPT1的高转运能力使得即使在黏膜功能受损的状态下,药物以及氨基酸氮仍能快速、高效地被肠道摄取。PEPT1的转录和转录后调控会随着营养状况和疾病状态的改变而发生,这表明该转运体在氨基酸吸收中起着重要作用。