Inhibition of pancreatic lipase in vitro by the covalent inhibitor tetrahydrolipstatin

Biochem J. 1988 Dec 1;256(2):357-61. doi: 10.1042/bj2560357.


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.

MeSH terms

  • Animals
  • Enzyme Inhibitors / pharmacology*
  • Hydrolases / antagonists & inhibitors
  • Lactones / pharmacology*
  • Lipase / antagonists & inhibitors*
  • Lipolysis / drug effects
  • Oleic Acids / metabolism
  • Orlistat
  • Pancreas / enzymology*
  • Swine
  • Time Factors
  • Triolein / metabolism


  • Enzyme Inhibitors
  • Lactones
  • Oleic Acids
  • Triolein
  • Orlistat
  • Hydrolases
  • Lipase