Mucosal Peptide Hydrolase and Brush-Border Marker Enzyme Activities in Three Regions of the Small Intestine of Rats with Experimental Uraemia

Abstract

1. The activities of nine peptide hydrolases and three non-peptidase brush-border marker enzymes have been quantified in crude homogenates prepared from the proximal, mild and distal regions of small-intestinal mucosa for sham-operated (n = 9) and uraemic (n = 14) rats. Abnormalities in enzyme activities were observed in all regions studied in the uraemic group, although no reduction in food intake occurred. 2. The proximal region of the small intestine from uraemic rats showed a general fall in enzyme activities associated with the brush-border. This fall was combined with a decline in mucosal protein content. In contrast, the mid and distal regions showed increased activity against the dipeptide tyrosyl-glycine. 3. It is proposed that the fall in brush-border enzyme activities in the proximal small intestine of uraemic rats is a response to the increased water intake associated with this, and presumably other, rat models of uraemia. The increased enzyme activity against tyrosyl-glycine found in the mid and distal regions of the small intestine of uraemic rats may be caused by an increased small-intestinal transit rate, but could be an attempt to maximize tyrosine absorption in response to decreased plasma tyrosine levels. 4. This study casts doubt on specific activities being the most useful units of enzyme activity, when measured in crude homogenates prepared from the proximal small intestine of uraemic rats. It also demonstrates that enzyme activities measured at a single site in the small intestine of uraemic rats may not be representative of the enzymatic changes occurring in the small-intestinal mucosa as a whole.

Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3

“…Though peak levels of hydrolysis products are observed in the plasma of humans at one-to-two hours post-consumption, it takes up to 24 h for levels to become undetectable [ 67 , 68 , 69 ]. Aminopeptidase A, the enzyme that is key for aspartame hydrolysis [ 64 ], is predominantly expressed and active in the mid and distal regions of the small intestine [ 70 ]. Proximal sections of the small intestine, the duodenum, and early jejunum may therefore be exposed to unmetabolized aspartame, which is able to bind to the sweet taste receptor, T1R3, expressed in these regions [ 71 ].…”

Increased protein level of PEPT1 intestinal H+-peptide cotransporter upregulates absorption of glycylsarcosine and ceftibuten in 5/6 nephrectomized rats

“…1). Considering the present results as well as the previous findings (7,9,11,31), the increase of the intestinal PEPT1 may have occurred before other morphological and enzymatic alteration after nephrectomy. These results support the hypothesis that the increase of absorption of [ 14 C]Gly-Sar and ceftibuten in the early phase of CRF was a specific event caused by the upregulation of PEPT1.…”

“…For example, the activities of sucrase and maltase were reduced (9), and the expression of intestinal cytochrome P-450 was downregulated in rats at 6 wk after nephrectomy (11). However, the activity of some dipeptidases was significantly but weakly increased or unchanged in the isolated brush-border membranes from the nephrectomized rat intestinal mucosa at 8 wk after surgery (31).…”

“…In chronic renal failure (CRF), morphological and enzymatic abnormalities have been found in the small intestinal mucosa of patients (7) and model rats at 12 wk after nephrectomy (9). For example, the activities of sucrase and maltase were reduced (9), and the expression of intestinal cytochrome P-450 was downregulated in rats at 6 wk after nephrectomy (11).…”

Native Chemical Ligation: A Boon to Peptide Chemistry

“…One of the major hurdles in developing conopeptides as therapeutics is overcoming their low oral bioavailability [65]. Peptides and proteins have low oral bioavailability due to degradation caused by digestive enzymes present in the intestinal lumen [79,80,81]. Secondly, the inability of peptides to permeate through membranes owing to size and polarity also results in low bioavailability [79,82].…”