title: Inhibition of pancreatic lipase in vitro by the covalent inhibitor tetrahydrolipstatin.
abstract: Tetrahydrolipstatin inhibits pancreatic lipase from several species, including man, with comparable potency. The lipase is progressively inactivated through the formation of a long-lived covalent intermediate, probably with a 1:1 stoichiometry. The lipase substrate triolein and also a boronic acid derivative, which is presumed to be a transition-state-form inhibitor, retard the rate of inactivation. Therefore, in all probability, tetrahydrolipstatin reacts with pancreatic lipase at, or near, the substrate binding or active site. Tetrahydrolipstatin is a selective inhibitor of lipase; other hydrolases tested were at least a thousand times less potently inhibited.
authors.affiliation: F. Hoffmann-La Roche & Co., Ltd., Pharmaceutical Research Department, Basel, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Hadváry
authors.forename: H
authors.initials: H
authors.lastname: Lengsfeld
authors.forename: H
authors.initials: H
authors.lastname: Wolfer
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006867:Hydrolases / Q000037:antagonists & inhibitors; D007783:Lactones / Q000494:pharmacology*; D008049:Lipase / Q000037:antagonists & inhibitors*; D008066:Lipolysis / Q000187:drug effects; D009829:Oleic Acids / Q000378:metabolism; D000077403:Orlistat; D010179:Pancreas / Q000201:enzymology*; D013552:Swine; D013997:Time Factors; D014304:Triolein / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D007783:Lactones; D009829:Oleic Acids; D014304:Triolein; D000077403:Orlistat; D006867:Hydrolases; D008049:Lipase