Small intestinal MUC2 synthesis in human preterm infants.

Mucin 2 (MUC2) is the structural component of the intestinal protective mucus layer, which contains high amounts of threonine in its peptide backbone. MUC2 synthesis rate might be a potential parameter for intestinal barrier function. In this study, we aimed to determine whether systemic threonine was used for small intestinal MUC2 synthesis and to calculate the MUC2 fractional synthetic rate (FSR) in human preterm infants. Seven preterm infants with an enterostomy following bowel resection for necrotizing enterocolitis received intravenous infusion of [U-(13)C]threonine to determine incorporation of systemic threonine into secreted MUC2 in intestinal outflow fluid. Small intestinal MUC2 was isolated using cesium chloride gradient ultracentrifugation and gravity gel filtration chromatography. MUC2-containing fractions were identified by SDS-PAGE/periodic acid-Schiff staining and Western blot analysis and were subsequently pooled. Isotopic enrichment of threonine, measured in MUC2 using gas chromatography isotopic ratio mass spectrometry, was used to calculate the FSR of MUC2. Systemically derived threonine was indeed incorporated into small intestinal MUC2. Median FSR of small intestinal MUC2 was 67.2 (44.3-103.9)% per day. Systemic threonine is rapidly incorporated into MUC2 in the small intestine of preterm infants, and thereby MUC2 has a very high synthesis rate.

[1]  D. Tibboel,et al.  A novel method to determine small intestinal barrier function in human neonates in vivo , 2006, Gut.

[2]  H. Barle,et al.  Synthesis rates of total liver protein and albumin are both increased in patients with an acute inflammatory response. , 2006, Clinical science.

[3]  B. Stoll,et al.  Threonine utilization is high in the intestine of piglets. , 2005, The Journal of nutrition.

[4]  T. Rossi,et al.  Small intestinal mucosa changes, including epithelial cell proliferative activity, of children receiving total parenteral nutrition (TPN) , 1993, Digestive Diseases and Sciences.

[5]  H. Offner,et al.  Improved sensitivity for detection and quantitation of glycoproteins on polyacrylamide gels , 1984, Experientia.

[6]  R. Harvey,et al.  Necrotizing Enterocolitis in Preterm Pigs Diet-Dependent Effects of Minimal Enteral Nutrition , 2003 .

[7]  B. Stoll,et al.  Parenteral nutrition results in impaired lactose digestion and hexose absorption when enteral feeding is initiated in infant pigs. , 2003, The American journal of clinical nutrition.

[8]  D. Breuillé,et al.  Development of a rapid and convenient method to purify mucins and determine their in vivo synthesis rate in rats. , 2002, Analytical biochemistry.

[9]  W. Walker Development of the Intestinal Mucosal Barrier , 2002, Journal of pediatric gastroenterology and nutrition.

[10]  B. Stoll,et al.  The pattern of intestinal substrate oxidation is altered by protein restriction in pigs. , 2001, Gastroenterology.

[11]  R. Wolfe,et al.  Basal muscle amino acid kinetics and protein synthesis in healthy young and older men. , 2001, JAMA.

[12]  M. Caplan,et al.  New concepts in necrotizing enterocolitis , 2001, Current opinion in pediatrics.

[13]  B. Stoll,et al.  Adaptive regulation of intestinal lysine metabolism. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[14]  J. Holst,et al.  Minimal enteral nutrient requirements for intestinal growth in neonatal piglets: how much is enough? , 2000, The American journal of clinical nutrition.

[15]  F. Schildberg,et al.  Determination of protein synthesis in human ileum in situ by continuous [1-(13)C]leucine infusion. , 2000, American journal of physiology. Endocrinology and metabolism.

[16]  M. Rennie,et al.  Rates of small intestinal mucosal protein synthesis in human jejunum and ileum. , 1999, American journal of physiology. Endocrinology and metabolism.

[17]  B. Stoll,et al.  Substrate oxidation by the portal drained viscera of fed piglets. , 1999, The American journal of physiology.

[18]  B. Stoll,et al.  Dietary and systemic phenylalanine utilization for mucosal and hepatic constitutive protein synthesis in pigs. , 1999, American journal of physiology. Gastrointestinal and liver physiology.

[19]  R. Ball,et al.  Threonine requirement of neonatal piglets receiving total parenteral nutrition is considerably lower than that of piglets receiving an identical diet intragastrically. , 1998, The Journal of nutrition.

[20]  B. Stoll,et al.  Catabolism dominates the first-pass intestinal metabolism of dietary essential amino acids in milk protein-fed piglets. , 1998, The Journal of nutrition.

[21]  B. Stoll,et al.  Enteral glutamate is the preferential source for mucosal glutathione synthesis in fed piglets. , 1997, The American journal of physiology.

[22]  D. Burrin,et al.  Enteral glutamate is almost completely metabolized in first pass by the gastrointestinal tract of infant pigs. , 1996, The American journal of physiology.

[23]  J. Dekker,et al.  Mucin gene structure and expression: protection vs. adhesion. , 1995, The American journal of physiology.

[24]  J. Dekker,et al.  Biosynthesis of human colonic mucin: Muc2 is the prominent secretory mucin. , 1994, Gastroenterology.

[25]  M. Fukuzawa,et al.  Total parenteral nutrition decreases luminal mucous gel and increases permeability of small intestine. , 1994, JPEN. Journal of parenteral and enteral nutrition.

[26]  D. Burrin,et al.  Growth and metabolism of gastrointestinal and skeletal muscle tissues in protein-malnourished neonatal pigs. , 1994, The American journal of physiology.

[27]  L. Johnson,et al.  Physiology of the gastrointestinal tract , 2012 .

[28]  P. Essén,et al.  Temporal responses of protein synthesis in human skeletal muscle to feeding , 1993, British Journal of Nutrition.

[29]  J. Patience,et al.  L-threonine transport in pig jejunal brush border membrane vesicles. Functional characterization of the unique system B in the intestinal epithelium. , 1992, The Journal of biological chemistry.

[30]  J. F. Burke,et al.  Splanchnic and whole body L-[1-13C,15N]leucine kinetics in relation to enteral and parenteral amino acid supply. , 1992, The American journal of physiology.

[31]  G J Strous,et al.  Mucin-type glycoproteins. , 1992, Critical reviews in biochemistry and molecular biology.

[32]  D. I. Edelstone,et al.  Oxygen consumption by the gastrointestinal tract and liver in conscious newborn lambs. , 1981, The American journal of physiology.

[33]  G. Lobley,et al.  Whole body and tissue protein synthesis in cattle , 1980, British Journal of Nutrition.

[34]  Portland Press Ltd Contribution of rat liver and gastrointestinal tract to whole-body protein synthesis in the rat , 1980 .

[35]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[36]  R. D. Marshall,et al.  Carbohydrates in protein. 4. The determination of mannose in hen's-egg albumin by radioisotope dilution. , 1962, The Biochemical journal.

[37]  A. Neuberger Carbohydrates in protein: The carbohydrate component of crystalline egg albumin. , 1938, The Biochemical journal.