Peptide absorption: a review of current concepts and future perspectives. K E Webb Jr, J C Matthews, D B DiRienzo. Journal of Animal Science, 1992, 70(10): 3248–3257.
Absorption of di- and tripeptides from the gastrointestinal tract is accepted as being an important biological phenomenon. The extent to which peptides are absorbed and the nutritional and metabolic significance of peptide absorption remain unclear. Evidence is strong for the existence of multiple peptide transport systems, including one type that is electrogenic in nature and that requires a proton motive force and cotransports two H+ for every peptide transported. The rate of absorption of peptides can be responsive to level of dietary intake and level of dietary protein. Peptide absorption seems to be an important physiological process in ruminants, and this process may account for a large portion of absorbed amino acids. An important new observation is that the nonmesenteric portion of the portal-drained viscera of the ruminant is a major site of peptide absorption. These new observations may result in a reshaping of the currently accepted theory concerning protein utilization by ruminants.
Board-invited review: Peptide absorption and utilization: Implications for animal nutrition and health. E. R. Gilbert, E. A. Wong, K. E. Webb Jr. Journal of Animal Science, 2008, 86(9):2135-2155.
Over the last 50 yr, the study of intestinal peptide transport has rapidly evolved into a field with exciting nutritional and biomedical applications. In this review, we describe from a historical and current perspective intestinal peptide transport, the importance of peptides to whole-body nutrition, and the cloning and characterization of the intestinal peptide transporter, PepT1. We focus on the nutritional significance of peptide transport and relate these findings to livestock and poultry. Amino acids are transported into the enterocyte as free AA by a variety of AA transporters that vary in substrate specificity or as di- and tripeptides by the peptide transporter, PepT1. Expression of PepT1 is largely restricted to the small intestine in most species; however, in ruminants, peptide transport and activity is observed in the rumen and omasum. The extent to which peptides are absorbed and utilized is still unclear. In ruminants, peptides make a contribution to the portal-drained visceral flux of total AA and are detected in circulating plasma. Peptides can be utilized by the mammary gland for milk protein synthesis and by a variety of other tissues. We discuss the factors known to regulate expression of PepT1 including development, diet, hormones, diurnal rhythm, and disease. Expression of PepT1 is detected during embryological stages in both birds and mammals and increases with age, a strategic event that allows for the immediate uptake of nutrients after hatch or birth. Both increasing levels of protein in the diet and dietary protein deficiencies are found to upregulate the peptide transporter. We also include in this review a discussion of the use of dietary peptides and potential alternate routes of nutrient delivery to the cell. Our goal is to impart to the reader the nutritional implications of peptide transport and dietary peptides and share discoveries that shed light on various biological processes, including rapid establishment of intestinal function in early neonates and maintenance of intestinal function during fasting, starvation, and disease states.
The effect of peptide absorption on PepT1 gene expression and digestive system hormones in rainbow trout (Oncorhynchus mykiss). Teresa Ostaszewska, Maciej Kamaszewski, Piotr Grochowski, Konrad Dabrowski, Tiziano Verri, Ercüment Aksakal, Iwona Szatkowska, Zuzanna Nowak, Stefan Dobosz. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 2010, 155(1): 107–114.
The present study evaluates the effect of protein source (dipeptides, free amino acids, and intact protein) on development and growth of Salmonid fish alevin. Specifically, we follow the expression of oligopeptide transporter protein PepT1 in the intestine of rainbow trout (Oncorhynchus mykiss). Fish were fed exogenously one of four diets: three formulated (lysyl–glycine dipeptide supplemented diet — PP, free lysine and glycine supplemented diet — AA, control diet with no lysine — CON) or commercial starter (Aller Futura — AF). Fish increased mean body weight 8 fold with PP- and AA-supplemented diets resulting in significantly higher weight gain than fish fed CON. Statistical analysis revealed a significant increase in relative PepT1 expression of fish fed experimental diets. Immunohistochemical staining with PepT1 antibody showed the presence of the transporter protein in the brush border membrane of the proximal intestinal enterocytes of fish from all experimental groups. Leptin immunoreactivity occurred not only in the gastric glands but also in proximal intestine and pyloric caeca of fish fed PP, AA and AF diets. Leptin immunoreactivity was also observed in hepatocyte cytoplasm and pancreatic acinar cells. Gastrin/CCK immunoreactive cells were present in the proximal intestine and pyloric caeca.
Improvement of intestinal peptide absorption by a synthetic bile acid derivative, cholylsarcosine. Susanne Michael, Marc Thöle, Ruth Dillmann, Alfred Fahr, Jürgen Drewe, Gert Fricker. European Journal of Pharmaceutical Sciences, 2000,10(2): 133–140.
The potential of the nontoxic bile salt derivative, cholylsarcosine, to enhance the intestinal absorption of peptides was investigated in vitro and in situ. The permeation of the two model peptides octreotide and vasopressin-[arg8] (desmopressin) and the paracellular marker FITC–Dextran 4000 across Caco-2 cell (originally derived from a human colorectal carcinoma) monolayers was studied in the absence and in the presence of bile acids, including cholylsarcosine (CS). The absorption of the peptides was also determined in situ in rats. The absolute absorption efficiency was calculated by determination of plasma levels after intravenous administration of the peptides. Cytotoxic properties of the bile acids were studied using the following assays: WST-1-transformation measuring mitochondrial dehydrogenase activity as an indicator of cell proliferation and cell viability, lactate dehydrogenase (LDH) release by the Caco-2 cells and assessment of the transepithelial electrical resistance. CS, cholyltaurine (CT) and chenodeoxycholic acid (CDCA) showed an enhancing effect on peptide permeation across Caco-2 cell monolayers with the rank order CDCA>CT≥CS, whereas ursodeoxycholic acid exhibited no absorption enhancement. Determination of the cytotoxic potential of the bile salts revealed the same rank order. In rats, octreotide and desmopressin were absorbed from the gastrointestinal-tract with moderate absorption efficiency. Coadministration of bile salts resulted in an increased absorption efficiency. The effect of CS was similar to that of CT. In conclusion, CS shows absorption enhancement properties and a relatively low cytotoxicity. It offers an alternative as absorption enhancer as compared to conventional bile acids which may have a potential cocarcinogenic risk.
Amino acid and peptide absorption from the gastrointestinal tract. Webb KE Jr. Federation proceedings, 1986, 45(8): 2268–71.
Dietary proteins are digested and amino acids from these are utilized by animals to meet body needs for maintenance and production. The form in which these amino acids are absorbed and how they may be transported in the blood seem less certain than once thought. Free amino acids are absorbed and transported in the plasma as well as possibly in the blood cells. These two pools may serve unique functions and therefore deserve individual attention. Peptides are absorbed by the enterocytes. Amino acids in the peptide form appear to be absorbed more readily than free amino acids. The question of whether these peptides are hydrolyzed in the cytosol of the enterocyte or whether they can pass intact into the circulation needs more attention. Evidence suggests that the portal appearance of peptides ranges from negligible contributions to as much as 70% of the amino acids appearing in plasma.
Intestinal absorption of protein hydrolysis products: a review. Webb KE Jr, Journal of Animal Science, 1990, 68(9): 3011–22.
Many experimental techniques have allowed researchers to probe the fate of hydrolysis products from proteins in the small intestine. An overview of amino acid and peptide absorption from the small intestine is presented with attention given to historical perspectives that have led to current concepts. Speculation about nutritional significance of these processes is offered. Species differences exist in site of amino acid absorption. Numerous mechanisms are available for the transport of amino acids, including Na(+)-dependent carriers (energy-requiring), Na(+)-independent carriers and diffusion. The relative contribution each transport system makes to absorption is dependent on substrate concentration. Individual amino acids are not absorbed with equal efficiency; methionine usually is absorbed in the greatest proportion. There are interactions among amino acids for transports by specific transport systems. Small peptides (mostly di- and tripeptides) are absorbed from the small intestine more rapidly than are free amino acids; peptides are transported by systems independent of those responsible for transporting free amino acids. Evidence exists that the active transport of these peptides is via a proton gradient. Although the concept that peptides are absorbed intact into the circulation is not universally accepted, evidence supporting the possibility of tissue utilization of these small peptides is accumulating.