Intestinal assimilation of a proline-containing tetrapeptide. Role of a brush border membrane postproline dipeptidyl aminopeptidase IV.

Abstract

A B S T R A C T The mechanism of hydrolysis and absorption of a proline-containing tetrapeptide, Leu-ProGly-Gly (10 mM) by rat intestine was examined in vivo by using jejunal perfusion methods. The peptide substrate and hydrolysis products were analyzed by use of an automated amino acid analyzer. Leucine, proline, and glycine were absorbed by the intestine at a significantly higher rate from the tetrapeptide than from an equivalent amino acid mixture. The analysis of the hydrolytic products in the lumen during in vivo perfusion of the tetrapeptide showed that two dipeptides, Leu-Pro and Gly-Gly, were the major products. These two dipeptides were also the major hydrolytic products when a purified rat intestinal brush border membrane preparation was incubated with Leu-ProGly-Gly. The rate of hydrolysis of the tetrapeptide was much higher than that for several other proline-containing peptides (Leu-Pro, Pro-Leu, and Pro-Gly-Gly) that were tested. Studies using Gly-Pro-,B-naphthylamide, a specific substrate for postproline dipeptidyl aminopeptidase IV, showed that this enzyme is mainly localized to the brush border membrane and is responsible for the hydrolysis of the tetrapeptide into the two dipeptides Leu-Pro and Gly-Gly. Thus, brush border membrane dipeptidyl aminopeptidase IV very likely plays an important role at the intestinal mucosal cell surface in the final stages of digestion of prolinecontaining peptides.

Human dipeptidyl peptidase IV gene promoter: tissue-specific regulation from a TATA-less GC-rich sequence characteristic of a housekeeping gene promoter

“…Our laboratory has long been interested in the structure and function of intestinal brush-border-membrane peptidases and other hydrolases [1][2][3][4]. Analysis of these enzymes has contributed greatly to our understanding of the overall processes involved in digestion and absorption in the small bowel.…”

“…Thus DPP IV is expressed in a select range of tissues. Several functional roles have been proposed for DPP IV, including digestion [1][2][3][4], participation in the thymocyte-activation cascade [8,9], participation in HIVinduced apoptosis [10], interactions with the substratum [11], modulation of hormonal activity [12], and hydrolysis of renal peptides [13].…”

Disturbed intestinal nitrogen homeostasis in a mouse model of high-fat diet-induced obesity and glucose intolerance

“…Smaller peptides are then cleaved by brush-border peptidases at the surface of epithelial cells to produce free amino acids (AA) (30%) and di-and tripeptides (70%). Among the peptidases that take part in the last step of protein catabolism, the dipeptidyl peptidase IV (DPPIV) plays a major role in the breakdown of oligopeptides into AAs (36). In the small intestine, various specific systems facilitate the transfer of AA across the brush-border membrane of the absorptive enterocytes.…”

Clinical relevance of intestinal peptide uptake

“…In particular, prolinecontaining oligopeptides are poorly hydrolyzed by most peptidases, yet are very important for assimilation of many normal dietary proteins with a high proline content (e.g., gliadin). Prolinespecific dipeptidases are also located in the brush border membrane and cytoplasmic portion of the cell and these serve to hydrolyze most prolinecontaining peptides (e.g., dipeptidyl aminopeptidase Ⅳ) [7] . Particularly important was the early observation that amino acids infused into human intestine in peptide form are more readily absorbed than if infused into the intestinal lumen as free amino acids [8] .…”