Pancreatic lipase, function

Goldstein, N. P. Epstein, J. H. and Roe, H. J. Studies of pancreatic function IV. A simplified method for determination of pancreatic lipase using aqueous tributyrin as substrate, with one hundred normal values by this method. J. Lab. Clin. Med. (1948), 33, 1047-1051. 

Figure 26-5. Principle of the 13C-mixed triglyceride breath test. Absorption of 13C-mixed triglycerides requires prior hydrolysis by pancreatic lipase (1), which leads to production of free fatty acids (stearic acid) and monoacylglycerol [2-(l-13C)octanoylglycerol]. These metabolites are incorporated into micelles, absorbed, and transported to the liver (2). Further degradation by hepatic enzymes and P-oxidation results in formation of 13C02, which is absorbed into the bloodstream, transported to the lung, and exhaled (3). Thus, exhalation of 13C02 reflects intestinal lipolysis and is a marker of pancreatic exocrine function.

Chlorotetaine is an irreversible inhibitor of glucosamine-6-phosphate synthetase and thereby interferes with ceil wall biosynthesis. The terminal steps of a synthesis of Chlorotetaine are shown in Scheme 6.15 in which deprotection of an iV-terminal amino group is a prelude to the final enzymatic hydrolysis of a methyl ester function.43 Critical to the success of the synthesis was the suppression of easy racemisation at the ring juncture in the ester hydrolysis step by using porcine pancreatic lipase. 

Bile is produced by hepatocytes from several essential components, including water, bile acids, cholesterol, phospholipids and bilirubin. Most of these substances are absorbed in the distal ileum and delivered to the hepatocyte via the portal vein. The liver excretes approximately 500-600 mL of bile each day, most of which is stored in the gallbladder. Bile acids have an important function in emulsifying lipids in the digestive tract, which improves digestion by pancreatic lipases. 

It is, however, the role of colipase, a cofactor unique to the pancreatic enzyme, that is of particular significance. CLP was originally believed to function by anchoring the lipase molecule to the bile salt-covered surface of the lipid micelle (Canioni et al., 1977 Verger et al., 1977), thereby playing a key role in the interfacial activation. The enhancement of activity of hPL in the presence of CLP is approximately 10-fold. Abousalham et al. (1992) used limited proteolytic degradation of pancreatic lipases by chymotrypsin as a tool to obtain information re-... 

As indicated in Fig. 9.20, lipase activities were measured as a function of the orlistat surface molar fraction. With aU lipases tested, the hydrolysis of dicaprin decreased sharply as the surface molar fraction of orlistat increased. The surface molar fractions of orlistat, which reduces lipase activity to 50% (uso), are 0.013%, 0.025% and 0.25% with PPL, RGL and HGL, respectively (Fig. 9.20 A) and 0.00025% with HPL (Fig. 9.20B). On the one hand, it should be remembered that the turnover rates of gastric and pancreatic lipases are quite different [115]. Consequently, the amounts of each hpase injected into the reaction compartment of the zero-order trough were different (see legend of Fig. 9.20), leading to various orh-stat/hpase molar ratios. On the other hand, we know that monolayer systems are characterized by a low specific surface (around 1 cm /cm ). As a consequence, only a small fraction of the injected enzyme is bound to the monomolecular film. 

Inhibition of Pancreatic Lipase on Oil Drop Pre-poisoned with Orlistat Tiss et al. [117] studied the partitioning of orhstat between the core and the surface of an oil drop, as a function of the orhstat concentration in the oil. The molar fraction of orhstat at the oil drop surface was eshmated using the Gibbs surface excess equation. With these data it becomes possible to express orhstat con-... 

Lowe, M.E. (2000) Properties and function of pancreatic lipase related protein 2. Bio-chimie 82, 997—1004. 

The present work investigates the action of pancreatic lipase on spread monolayers of ethylene glycol adipate oligomers. The tritiated hydrolysis products of the uniformly labeled substrate escape into the subphase. Surface radioactivity measurements allow us to determine the substrate concentration at the interface (2, 3) and the extent of the enzymic reaction. The kinetics were investigated as a function of subphase pH and temperature and substrate length and concentration. By... 

Lipases are another important group of hydrolases. The most commonly used example is porcine pancreatic lipase (PPL). Lipases tend to function best at or above the solubility limit of the hydrophobic substrate. In the presence of water, the substrate forms an insoluble phase (micelles) the concentration at which this occurs is called the critical micellar concentration. The enzyme is activated by a conformational change that occurs in the presence of the micelles and results in the opening of the active site. Lipases work best in solvents that can accommodate this activation process. PPL is often used as a relatively crude preparation called pancreatin or steapsin. The active site in PPL has not been as precisely described as the one for PLE. There are currently two different models, but they sometimes make contradictory predictions. It has been suggested that the dominant factors in binding are the hydrophobic and polar pockets (sites B and C in Figure 2.29), but that the relative location of the catalytic site is somewhat flexible and can accommodate to the location of the hydrolyzable substituent. ... 

Although the concentrations of pancreatic lipase and bile salts are low in the intestinal lumen of the newborn infant, the fat of human milk is still readily absorbed. This is true because lingual and gastric lipases produced by the infant partially compensate for the lower levels of pancreatic lipase. The human mammary gland also produces lipases that enter the milk. One of these lipases, which requires lower levels of bile salts than pancreatic lipase, is not inactivated by stomach acid and functions in the intestine for a number of hours. 

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