Morphological and functional changes in the enterocyte induced by fructose.
In the presence of 10-50 mM-fructose, enterocytes of organ-cultured pig intestinal-mucosal explants fail to glycosylate correctly their newly synthesized microvillar enzymes, and instead degrade them [Danielsen (1989) J. Biol. Chem. 264, 13726-13729]. In the present work, this degradation was shown to occur extremely rapidly as the microvillar enzyme aminopeptidase N (EC 3.4.11.2) was hardly detectable after a 10 min pulse with [35S]methionine. The abnormal biosynthesis of membrane glycoproteins affected both the morphology and the function of the Golgi complex as well as the microvillar membrane. Thus the stack of Golgi cisternae was condensed and devoid of dilated rims, and the secretion of a non-glycosylated protein, apolipoprotein A-1, was almost completely blocked in the presence of fructose, showing that transport through the secretory pathway is disturbed even for proteins unaffected by the defective glycosylation. The microvilli of the brush-border membrane were markedly shortened (by about 40%) in the presence of fructose, and incorporation of newly made actin into the microvillar cytoskeleton was similarly decreased. By affecting membrane glycoprotein synthesis, the common dietary sugar fructose thus profoundly perturbs the exocytic membrane traffic in the enterocyte.
Department of Biochemistry C, The Panum Institute, University of Copenhagen, Denmark.
E M
EM
Danielsen
G H
GH
Hansen
L L
LL
Wetterberg
D000626:Aminopeptidases / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D018826:CD13 Antigens; D002458:Cell Fractionation; D004591:Electrophoresis, Polyacrylamide Gel; D005632:Fructose / Q000378:metabolism / Q000494:pharmacology*; D006031:Glycosylation; D006056:Golgi Apparatus / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D007976:Leupeptins / Q000378:metabolism; D008358:Mannose / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D008871:Microvilli / Q000201:enzymology; D009924:Organ Culture Techniques; D013552:Swine
D016632:Apolipoprotein A-I; D007976:Leupeptins; D008565:Membrane Proteins; D005632:Fructose; D000626:Aminopeptidases; D018826:CD13 Antigens; C032854:leupeptin; D008358:Mannose