Heparin-modulated binding of pancreatic lipase and uptake of hydrolyzed triglycerides in the intestine.
Utilizing small intestine membranes that contain heparin (50 micrograms/mg protein), binding of triglyceride lipase (homogeneous 52 kDa, specific activity, 70 nmol/mg.h) to membranes was shown to be concentration dependent and saturable, and it was characterized by a single dissociation constant (KD = 86 +/- 16 nM) with a maximal binding capacity of 54 +/- 8 pmol/mg of vesicle protein. Specific binding was decreased in a concentration-dependent manner by the addition of exogenous heparin, and binding was virtually eliminated (less than 6% control values) by pretreatment of membranes with bacterial heparinase. Cultured intestinal epithelial cells (CaCo-2), shown to possess membrane-associated heparin, also bound pancreatic triglyceride lipase in a specific and saturable manner, with KD = 77 +/- 12 nM and Bmax = 13.7 +/- 6 pmol/10(6) cells. Soluble heparin not only decreased binding, but it also diminished the enzyme-mediated cellular uptake of [14C]oleate from [14C]triolein by over 75%. Therefore, intestinal heparin, a component of the brush border membrane, localizes pancreatic triglyceride lipase in a receptor-like manner to the plasma membrane to promote the subsequent absorption of fatty acids derived from hydrolyzed triglycerides.
Bosner
M S
MS
Department of Medicine, Jewish Hospital of Saint Louis, Washington University Medical Center, Missouri 63110.
Gulick
T
T
Riley
D J
DJ
Spilburg
C A
CA
Lange
L G
LG
D000230:Adenocarcinoma; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D003110:Colonic Neoplasms; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008049:Lipase / Q000378:metabolism*; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism*; D010179:Pancreas / Q000201:enzymology*; D011485:Protein Binding; D011817:Rabbits; D014304:Triolein / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D009829:Oleic Acids; D014304:Triolein; D019301:Oleic Acid; D006493:Heparin; D008049:Lipase