Regulation of intestinal peptidases by nutrients in human fetuses and children.
Nutrient interactions during intestinal digestion has been established in animals. The present study investigated the effect of different nutrients on intestinal dipeptidase, tripeptidase, carboxypeptidase (EC 3.4.12.-) and aminopeptidase N (ApN) (EC 3.4.11.2) activities in human fetuses and children. The effect of nutrients on isolated porcine kidney ApN was also studied. Sucrose, lactose and tributyrin had no effect on di-, tri-, and carboxypeptidase activities of mucosal homogenates, but tributyrin significantly (20-50%) inhibited both fetal and postnatal ApN activity in the small intestine and colon. The pH-independent inhibition of ApN is specific for tributyrin and to the product of its hydrolysis, butyric acid. Glycerol, triolein, and natural oils did not affect ApN activity. The inhibition of ApN by tributyrin was dose and time dependent and occurred in enterocyte brush border membranes as well as in the purified enzyme from porcine kidney. The kinetics of the purified ApN showed that the tributyrin effect is primarily competitive and associated mainly with an increase in K(m). These observations demonstrate the possibility of intestinal and kidney ApN regulation by lipids and products of their hydrolysis. We speculate that nutrient interactions arose quite early in the evolution and represent a mechanism for the regulation of food digestion.
Kushak
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RI
Combined Program of Pediatric Gastroenterology and Nutrition, Harvard Medical School, Boston University School of Medicine, Massachusetts General Hospital 02114-2698, USA. kushak.rafail@mgh.harvard.edu
Winter
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HS
D002648:Child; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005333:Fetus / Q000201:enzymology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007421:Intestine, Small / Q000196:embryology / Q000201:enzymology* / Q000502:physiology; D007700:Kinetics; D009747:Nutritional Physiological Phenomena; D010447:Peptide Hydrolases / Q000378:metabolism*; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology; D014220:Trialkyltin Compounds / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism
D004791:Enzyme Inhibitors; D014220:Trialkyltin Compounds; D014280:Triglycerides; C011559:tributyltin; D010447:Peptide Hydrolases