Drugs online research references
Biochim Biophys Acta. 1988 Oct 14;962(3):308-16.
Mode of action of tetrahydrolipstatin: a derivative of the naturally occurring lipase inhibitor lipstatin.
Borgstrom B.
Department of Physiological Chemistry, University of Lund, Sweden.
Tetrahydrolipstatin is a specific lipase inhibitor derived from lipstatin, a lipid produced by Streptomyces toxytricini. In addition to pancreatic lipase, it is shown in the present study that tetrahydrolipstatin also inhibits human gastric lipase, carboxyl ester lipase (cholesterol esterase) of pancreatic origin and the closely related bile-salt-stimulated lipase of human milk. It does not inhibit the exocellular lipase from Rhizopus arrhizus or a lipase recently isolated from Staphylococcus aureus. In the presence of a water-insoluble substrate, such as tributyrin, the inhibition has the characteristics of an irreversible inactivation of the uncompetitive type, thus indicating that an enzyme.substrate.inhibitor complex is formed, which cannot undergo further reaction to yield the normal product. This reaction probably takes place at the aqueous/oil interface of the substrate. In aqueous solution, in the absence of substrate, the inhibition of carboxyl ester lipase by tetrahydrolipstatin has the characteristics of being reversible, and finally becomes of a temporary nature analogues to the trypsin-trypsin inhibitor system. It is suggested that an enzyme-inhibitor complex of an acyl-enzyme type is formed that is slowly hydrolysed, with water as the final acceptor, leaving an intact enzyme and an inactive form of the inhibitor. The enzyme thus consumes the inhibitor, which undergoes a chemical conversion, as indicated by a change in mobility in an appropriate thin-layer chromatographic system, indicating an increase in hydrophilicity. Evidence is presented that the reaction product is an acid and that the functional group of tetrahydrolipstatin is the beta-lactone reacting with the active site of the enzyme.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3167082&dopt=Abstract
word match xenical online literature
Biochem J. 1988 Dec 1;256(2):357-61.
Inhibition of pancreatic lipase in vitro by the covalent inhibitor tetrahydrolipstatin.
Hadvary P, Lengsfeld H, Wolfer H.
F. Hoffmann-La Roche & Co., Ltd., Pharmaceutical Research Department, Basel, Switzerland.
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.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3223916&dopt=Abstract
word match xenical online literature
Int J Obes. 1987;11 Suppl 3:35-42.
Studies on the antiobesity activity of tetrahydrolipstatin, a potent and selective inhibitor of pancreatic lipase.
Hogan S, Fleury A, Hadvary P, Lengsfeld H, Meier MK, Triscari J, Sullivan AC.
Hoffmann-La Roche Inc., Nutley, NJ 07110.
In summary, THL is a potent inhibitor of pancreatic lipase, which is both selective and irreversible in its action in vitro. It is also likely that THL inhibits pancreatic lipase in vivo, since its acute administration to mice and squirrel monkeys suppresses absorption of dietary triglycerides, without an apparent alteration in the absorption of fatty acids. The marked loss in body weight and carcass fat of DIO rats with subchronic administration of THL strongly suggests that inhibition of pancreatic lipase is a feasible strategy for the treatment of obesity. Whether obese humans will overeat in response to a reduction in body energy stores is not known. However, it is probable that compliance to a therapy which maintains the present level of food intake while inducing excretion of dietary fat, will be greater than a reducing diet alone or conjunction with the currently available antiobesity drugs.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3440690&dopt=Abstract
word match xenical online literature
Herbs and Pharmaceuticals Online ||
Hair Million herbal formula for hair loss and hair growth ||
Antibiotics and prescription medications online literature ||