Lipstatin, an inhibitor of pancreatic lipase, produced by Streptomyces toxytricini. I. Producing organism, fermentation, isolation and biological activity.
Lipstatin, a new and very potent inhibitor of pancreatic lipase (the key enzyme of intestinal fat digestion) was isolated from Streptomyces toxytricini. Lipstatin contains a beta-lactone structure that probably accounts for the irreversible lipase inhibition. The IC50 of lipstatin for pancreatic lipase is 0.14 microM. In mice triolein absorption was dose-dependently inhibited by lipstatin, whereas oleic acid was absorbed normally. Other pancreatic enzymes, such as phospholipase A2 and trypsin, were not inhibited even at an inhibitor concentration of 200 microM.
Weibel
E K
EK
Central Research Units, F. Hoffmann-La Roche & Co., Ltd., Basel, Switzerland.
Hadvary
P
P
Hochuli
E
E
Kupfer
E
E
Lengsfeld
H
H
D000818:Animals; D004041:Dietary Fats / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000096:biosynthesis* / Q000302:isolation & purification / Q000494:pharmacology; D005285:Fermentation; D007408:Intestinal Absorption / Q000187:drug effects; D007783:Lactones / Q000096:biosynthesis* / Q000302:isolation & purification / Q000494:pharmacology; D008049:Lipase / Q000037:antagonists & inhibitors*; D051379:Mice; D013302:Streptomyces / Q000032:analysis* / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D004041:Dietary Fats; D004791:Enzyme Inhibitors; D007783:Lactones; D014280:Triglycerides; C054164:lipstatin; D008049:Lipase