The oligopeptide transporter (Pept-1) in human intestine: biology and function.
The oligopeptide transporter (Pept-1), which is located in the intestinal brush border membrane, provides a major mechanism for protein absorption in the human intestine. Expression cloning of the gene encoding Pept-1 has predicted a 78,810-kilodalton protein consisting of 708 amino acid residues and possessing 12 putative membrane-spanning domains. The characterization of its function by in vivo and in vitro studies has shown that (1) it transports dipeptides and tripeptides but not free amino acids or peptides with more than three amino acid residues, and (2) its driving force for uphill transport requires proton binding and presence of an inside-negative membrane potential. There has also been cloning of a membrane protein (HPT-1) which appears to be associated with the oligopeptide transporter. However, the nature of association has not yet been determined. A human intestinal cell line (Caco-2), which expresses Pept-1, has been used to investigate the effects of metabolic and pathological factors on dipeptide transport. These studies suggest that the insulin stimulates dipeptide transport by increasing membrane insertion of oligopeptide transporter from a preformed cytoplasmic pool, and cholera toxin decreases dipeptide transport by inhibiting the activity of Pept-1 through an increase in the intracellular concentration of adenosine 3',5'-cyclic monophosphate. Lastly, Pept-1 seems to play important roles in nutritional and pharmacological therapies; for example, it has allowed the use of oligopeptides as a source of nitrogen for enteral feeding and the use of oral route for delivery of peptidomimetic drugs such as beta-lactam antibiotics.
Adibi
S A
SA
Department of Medicine, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA.
D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D000074011:Peptide Transporter 1; D027981:Symporters
D002352:Carrier Proteins; D000074011:Peptide Transporter 1; C082186:SLC15A1 protein, human; D027981:Symporters