Pancreatic enzymes lipase

Seligson, D. Nephelometric determination of pancreatic enzymes. II lipase. Clin. Chim. Acta (1973), 173-178. 

Pancreatic enzyme doses are initiated at 500 to 1000 units/kg per meal of lipase component with half-doses given with snacks. Infants are typically started at 1500 to 2500 units of... 

Supplementation with pancreatic enzymes may reduce the pain and fatty diarrhea associated with chronic pancreatitis (Table 20-3). Best results are achieved in patients who have mild non-alcoholic pancreatic disease. Common pancreatic enzyme supplements contain lipase, amylase, and protease in varying proportions. Thus, the dose can be tailored to the patient s requirement for exogenous enzyme supplementation and response to therapy. 

Non-enteric-coated pancreatic enzyme supplements can be used for initial therapy. The relative dose of amylase, lipase, and protease may be increased until control of pain and fatty diarrhea is achieved or the patient experiences intolerable side effects. If pain and diarrhea control are achieved, the patient can be transitioned to an enteric-coated supplement to maximize compliance. A reasonable example starting regimen is Viokase-8, six tablets with each meal and at bedtime, given with famotidine 20 mg at bedtime. 

Pancreatic enzyme supplements should be taken immediately prior to meals to aid in the digestion and absorption of food. Alternately, patients can supplement their diet with medium chain triglycerides (MCTs) or ingest foods rich in MCTs since they do not require pancreatic enzymes for absorption. An appropriate regimen incorporates the successful doses of each enzyme (amylase, lipase, and protease) from the starting non-enteric-coated regimen. As with the previous example, a patient stabilized on Viokase-8, six tablets with each meal, can be transitioned to Pancrease MT-16 three tablets with meals. The famotidine can then be discontinued. 

Lipase A pancreatic enzyme that cleaves lipids. 

Pancreatic enzyme activity is very low in premature neonates. Lipase activity increases 20-fold in the first 9 months of life. Since concentration of bile salts is also... 

Some of the pancreatic enzymes in the lumen include pancreatic amylase, pancreatic lipase, elastase, trypsin, a-chymotrypsin, and carboxypeptidase A. For example, the aspirin derivatives aspirin phenylalanine ethyl ester, aspirin phenyllactic ethyl ester, and aspirin phenylalanine amide have been studied as substrates for carboxypeptidase A [67,68], with the phenylalanine ethyl ester derivative proving to be the best substrate. This study indicated that the carboxypeptidase A may serve as a reconversion site for many drug derivatives. 

Release of active pancreatic enzymes directly causes local or distant tissue damage. Trypsin digests cell membranes and leads to the activation of other pancreatic enzymes. Lipase damages fat cells, producing noxious substances that cause further pancreatic and peripancreatic injury. 

Most patients with malabsorption require pancreatic enzyme supplementation (Fig. 28-2). The combination of pancreatic enzymes (lipase, amylase, and protease) and a reduction in dietary fat (to less than 25 g/meal) enhances nutritional status and reduces steatorrhea. An initial dose containing about 30,000 international units of lipase and 10,000 international units of trypsin should be given with each meal. 

Oral pancreatic enzyme supplements are available as powders, uncoated or coated tablets, capsules, enteric-coated spheres and microspheres, or enteric-coated microtablets encased in a cellulose or gelatin capsule (Table 28-2). Microencapsulated enteric-coated products are not superior to recommended doses of conventional non-enteric-coated enzyme preparations. The quantity of active lipase delivered to the duodenum appears to be a more important determinant in pancreatic enzyme replacement therapy than the dosage form. GI side effects appear to be dose related but occur less frequently with enteric-coated products. 

The presence or absence of pancreatic enzymes can only be satisfactorily decided by intraduodenal intubation and direct examination of samples of small intestinal contents after the administration of a suitable stimulus to pancreatic secretion (Fll). It is not sufficient to look at one enzyme only, such as trypsin, since a specific deficiency of lipase can occur (Sll). Assessment of the degree of hydrolysis of fat in the stools is quite unreliable as a guide to pancreatic enzyme activity (CIO). 

Pancreatic enemies (B) from slaughtered animals are used to relieve excretory insufficiency of the pancreas ( disrupted digestion of fats steatorrhea, inter alia). Normally, secretion of pancreatic enzymes is activated by cholecystokinin ancreozymin, the en-terohormone that is released into blood from the duodenal mucosa upon contact with chyme. With oral administration of pancreatic enzymes, allowance must be made for their partial inactivation by gastric acid (the lipases, particularly). Therefore, they are administered in acid-resistant dosage forms. 

Various pancreatic enzymes hydrolyze lipids, including lipase with its auxiliary protein colipase (see p. 270), phospholipase A2, and sterol esterase. Bile salts activate the lipidcleaving enzymes through micelle formation (see below). 

Triacylglycerol Upases [EC 3.1.1.3] (also known as triglyceride lipases, tributyrases, or simply as lipases) catalyze the hydrolysis of a triacylglycerol to produce a diac-ylglycerol and a fatty acid anion. The pancreatic enzyme acts only on an ester-water interface the outer ester links in the substrate are the ones which are preferentially... 

Cystic fibrosis can obstruct pancreatic ducts due to mucous plugging and impaired secretion of pancreatic enzymes such as lipase and phospholipases, which decreases hydrolysis and uptake oftri-acylglycerols. 

Mecfianism of Action A gastric and pancreatic lipase inhibitor that inhibits absorption of dietary fats by inactivating gastric and pancreatic enzymes. Therapeutic Effect Resulting caloric deficit may positively affect weight control. 

Steatorrhea occurs in patients whose lipase output is at 10% or less of normal. Lipase and other pancreatic enzyme insufficiencies are observed in cystic fibrosis and chronic alcoholic pancreatitis. Patients with various liver diseases may also present with steatorrhea [18]. For these patients, pancreatic enzymes—mainly lipase, protease, and amylase—extracted with alcohol from porcine pancreases have been shown to provide amelioration of diarrhea. These enzymes are enriched and formulated in... 

Gastrointestinal enzyme activities tend to be lower in the newborn than in the adult. Activities of -amylase and other pancreatic enzymes in the duodenum are low in infants up to 4 months of age. Neonates also have low concentrations of bile acids and lipase, which may decrease the absorption of lipid-soluble drugs. 

Exocrine pancreatic insufficiency is most commonly caused by cystic fibrosis, chronic pancreatitis, or pancreatic resection. When secretion of pancreatic enzymes falls below 10% of normal, fat and protein digestion is impaired and can lead to steatorrhea, azotorrhea, vitamin malabsorption, and weight loss. Pancreatic enzyme supplements, which contain a mixture of amylase, lipase, and proteases, are the mainstay of treatment for pancreatic enzyme insufficiency. Two major types of preparations in use are pancreatin and pancrelipase. Pancreatin is an alcohol-derived extract of hog pancreas with relatively low concentrations of lipase and proteolytic enzymes, whereas pancrelipase is an enriched preparation. On a per-weight basis, pancrelipase has approximately 12 times the lipolytic activity and more than 4 times the proteolytic activity of pancreatin. Consequently, pancreatin is no longer in common clinical use. Only pancrelipase is discussed here. 

Pancreatic enzyme supplements are well tolerated. The capsules should be swallowed, not chewed, because pancreatic enzymes may cause oropharyngeal mucositis. Excessive doses may cause diarrhea and abdominal pain. The high purine content of pancreas extracts may lead to hyperuricosuria and renal stones. Several cases of colonic strictures were reported in patients with cystic fibrosis who received high doses of pancrelipase with high lipase activity. These high-dose formulations have since been removed from the market. 

In the duodenum, dietary lipids are degraded by pancreatic enzymes triacylglycerol by pancreatic lipase, phospholipids by phospholipase A2 and lysophospholipase, and cholesteryl esters by cholesterol esterase. Enzyme release from the pancreas is controlled by cholecystokinin, produced by cells in the intestinal mucosa. 

These agents are administered to aid in the digestion of food. The primary digestant preparations contain pancreatic enzymes or bile salts. Pancreatic enzymes such as amylase, trypsin, and lipase are responsible for digestion of carbohydrates, proteins, and lipids, respectively. These enzymes are normally synthesized in the pancreas and secreted into the duodenum via the pancreatic duct. Bile salts are synthesized in the liver, stored in the gallbladder, and released into the duodenum via the common bile duct. Bile salts serve to emulsify lipids in the intestinal tract and are important in lipid digestion and absorption. 

The search for intestinal cholesterol transporters extended for many years, beginning with a debate about whether or not it was even a protein-facilitated process (4, 5). The pancreatic enzyme carboxyl ester lipase (CEL, also called cholesterol esterase) was believed to be important to this process (6,7) and several companies devoted considerable resources to the development and testing of compounds to inhibit CEL, with mixed results (8-10). These efforts were abandoned in the mid-1990s, however, after studies with gene-knockout mice demonstrated that the enzyme was important only for absorption of cholesteryl ester (11, 12), which is a minor component of dietary cholesterol and is present at very low levels in bile. Interestingly, CEL is also found in liver where it has been shown to affect HDL metabolism (13). Thus, it may ultimately play an important role in cholesterol metabolism and may yet prove to be a useful drug target for CVD treatment (Camarota and Howies, unpublished). 

Lipase (EC 3.1.1.3). Among the pancreatic enzymes applied to diagnose AP is lipase, which is released to blood similarly to amylase after the pancreas epithelial structure has been damaged. The determination of lipase activity has a higher diagnostic sensitivity (87.2-98%) in AP diagnosis than amylase (G12, L16) (Table 1). A five-to sixfold increase in the enzyme activity is observed... 

Four major enzyme groups are secreted lipolytic, proteolytic, amylolytic, and nucleic acid splitting enzymes. These pancreatic enzymes, some of which are secreted in multipile forms, possess specificities complementary to die intestinal membrane-bound enzymes (Tabic 1). Fresh, uncontsnkinated pancreatic juice is without proteolytic activity because these enzymes am in the form of inactive zymogens. An important fraction of the calcium in pancreatic juice accompanies the enzymes, especially ct-amylase. Human pancreatic juice is moat dose to that of the pig, with high proportions of lipase and a-amylase in comparison with other mammals [1]. Therefore, pig pancreas extract, pancreatin, has up to now been die oreferred enzvme source for therapeutic tuncreas substitution. 

Pancreatic lipase is rapidly inactivated at pH values less than 4 [25] (Figs. 3 and 5], which has important consequences in the development of galenic formulations for pancreatic enzyme replacement. 

Like pancreatic lipase, this enzyme is clearly dependent on a lipid/water interface for maximal activity, where it also may reach a very high catalytic rale, Abo like pancreatic lipase, it is not inhibited by serine esterase inhibitors like DFP orPMSF. 

Abstract The major enzymatic barrier to the absorption of macromolecules, particularly therapeutic peptides, is the pancreatic enzymes the peptidases, nucleases, lipases and esterases that are secreted in considerable quantities into the intestinal lumen and rapidly hydrolyse macromolecules and lipids. In the case of the peptidases, they work in a co-ordinated fashion, whereby the action of the pancreatic enzymes is augmented by those in the brush borders of the intestinal cells. The sloughing-off of mucosal cells into the lumen also furnishes a mixture of enzymes that are a threat to macromolecules. As the specificity and activity of the enzymes are not always predictable, during pharmaceutical development it is important to test the stability of therapeutic macromolecules, and novel macromolecular-containing or lipid-containing formulations, in the presence of mixtures of pancreatic enzymes and bile salts, or in animal intestinal washouts or ideally, aspirates of human intestinal contents. 

Triglycerides are hydrolyzable into their component fatty adds and glycerol. They are espedally susceptible to alkaline hydrolysis. If KOH or NaOH is used, the process is saponification and the products, sodium and potassium salts of fatty adds, are called soaps. In the human organism, triglycerides are hydrolyzed by various esterases called lipases. These enzymes are quite spedfic, and they do not necessarily remove all three fatty add molecules from a triglyceride molecule. Thus, pancreatic lipase, the main lipid digestive enzyme of the small intestine, catalyzes the removal of fatty acids from positions 1 and 3 only. 

Dietary triglycerides are hydrolyzed in the small intestine by pancreatic lipase. This enzyme action is associated with a cofactor, colipase, also a pancreatic protein, molecular weight (MW) 12,000, which helps to anchor lipase to the fat droplets. Without colipase, lipase is rapidly denatured. Colipase is apparently secreted by the pancreas as a zymogen and is activated to its active form in the small intestine by trypsin. Pancreatic lipase appears in the circulation in large amounts during acute pancreatitis. 

The patient also was advised to change his dietary habits by avoiding large meals and eating several smaller or medium meals. He was treated with pancreatin, a medication containing a mixture of porcine pancreatic enzymes, including lipase, amylase, and proteases, with the dosage determined by units of lipase activity (Layer and... 

Small quantities of pancreatic enzymes are released from the pancreas into the bloodstream even physiologically and are detectable as low serum activities and/or concentrations of lipase, amylase, trypsinogen, and chymotrypsino-gen, respectively. Since progressive destruction of the organ occurs in chronic pancreatitis, this should theoretically be reflected by decreased serum enzymes, but so far these tests are not clinically useful because of their low accuracy. 

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