Pancreatic lipase
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Triglyceride lipases () are a
family Family (from la, familia) is a group of people related either by consanguinity (by recognized birth) or affinity (by marriage or other relationship). The purpose of the family is to maintain the well-being of its members and of society. Idea ...
of lipolytic enzymes that hydrolyse ester linkages of triglycerides. Lipases are widely distributed in animals, plants and prokaryotes. At least three tissue-specific
isozyme In biochemistry, isozymes (also known as isoenzymes or more generally as multiple forms of enzymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. Isozymes usually have different kinetic parameters (e.g. dif ...
s exist in higher vertebrates, pancreatic, hepatic and gastric/lingual. These lipases are closely related to each other and to lipoprotein lipase (), which hydrolyses triglycerides of chylomicrons and very
low density lipoprotein Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall densit ...
s (VLDL). The most conserved region in all these proteins is centred on a serine residue which has been shown to participate, with a histidine and an aspartic acid residue, in a charge relay system. Such a region is also present in lipases of prokaryotic origin and in lecithin-cholesterol acyltransferase () (LCAT), which catalyzes fatty acid transfer between phosphatidylcholine and cholesterol.


Human pancreatic lipase

''Pancreatic lipase'', also known as ''pancreatic triacylglycerol lipase'' or ''steapsin'', is an
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
secreted from the
pancreas The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an en ...
. As the primary lipase enzyme that hydrolyzes (breaks down) dietary
fat In nutrition, biology, and chemistry, fat usually means any ester of fatty acids, or a mixture of such compounds, most commonly those that occur in living beings or in food. The term often refers specifically to triglycerides (triple est ...
molecules in the human digestive system, it is one of the main
digestive enzyme Digestive enzymes are a group of enzymes that break down polymeric macromolecules into their smaller building blocks, in order to facilitate their absorption into the cells of the body. Digestive enzymes are found in the digestive tracts of anima ...
s, converting
triglyceride A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from ''wikt:tri-#Prefix, tri-'' and ''glyceride''). Triglycerides are the main constituents of body fat in humans and other ...
substrates like 1 found in ingested oils to
monoglyceride Monoglycerides (also: acylglycerols or monoacylglycerols) are a class of glycerides which are composed of a molecule of glycerol linked to a fatty acid via an ester bond. As glycerol contains both primary and secondary alcohol groups two differen ...
s 3 and
free fatty acid In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, fr ...
s 2a and 2b.Peter Nuhn: ''Naturstoffchemie'', S. Hirzel Wissenschaftliche Verlagsgesellschaft, Stuttgart, 2. Auflage, 1990, S. 308−309, .
Bile salts Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts. Primary b ...
secreted from the
liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
and stored in
gallbladder In vertebrates, the gallbladder, also known as the cholecyst, is a small hollow organ where bile is stored and concentrated before it is released into the small intestine. In humans, the pear-shaped gallbladder lies beneath the liver, although ...
are released into the duodenum, where they coat and emulsify large fat droplets into smaller droplets, thus increasing the overall surface area of the fat, which allows the lipase to break apart the fat more effectively. The resulting
monomers In chemistry, a monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization. Classification Mo ...
(2 free fatty acids and one 2-monoacylglycerol) are then moved by way of
peristalsis Peristalsis ( , ) is a radially symmetrical contraction and relaxation of muscles that propagate in a wave down a tube, in an anterograde direction. Peristalsis is progression of coordinated contraction of involuntary circular muscles, whic ...
along the small intestine to be absorbed into the lymphatic system by a specialized vessel called a lacteal. Unlike some pancreatic enzymes that are activated by
proteolytic cleavage Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called proteases, ...
(e.g.,
trypsinogen Trypsinogen () is the precursor form (or zymogen) of trypsin, a digestive enzyme. It is produced by the pancreas and found in pancreatic juice, along with amylase, lipase, and chymotrypsinogen. It is cleaved to its active form, trypsin, by ent ...
), pancreatic lipase is secreted in its final form. However, it becomes efficient only in the presence of colipase in the duodenum. In humans, pancreatic lipase is encoded by the PNLIP
gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.


Human proteins containing this domain

* LIPC *
LIPG Endothelial lipase (LIPG) is a form of lipase secreted by vascular endothelial cells in tissues with high metabolic rates and vascularization, such as the liver, lung, kidney, and thyroid gland. The LIPG enzyme is a vital component to many biologic ...
* LIPH * LIPI * LPL * PLA1A *
PNLIP Triglyceride lipases () are a family of lipolytic enzymes that hydrolyse ester linkages of triglycerides. Lipases are widely distributed in animals, plants and prokaryotes. At least three tissue-specific isozymes exist in higher vertebrates, ...
* PNLIPRP1 * PNLIPRP2 * PNLIPRP3


Diagnostic importance

Pancreatic lipase is secreted into the duodenum through the duct system of the pancreas. Its concentration in serum is normally very low. Under extreme disruption of pancreatic function, such as pancreatitis or pancreatic adenocarcinoma, the pancreas may begin to autolyse and release pancreatic enzymes including pancreatic lipase into serum. Thus, through measurement of serum concentration of pancreatic lipase, acute pancreatitis can be diagnosed.


Inhibitors

Lipase inhibitors such as
orlistat Orlistat, sold under the brand name Xenical among others, is a medication used to treat obesity. Its primary function is preventing the absorption of fats from the human diet by acting as a lipase inhibitor, thereby reducing caloric intake. It ...
can be used as a treatment for obesity. For label updates se
FDA index page for NDA 020766
/ref> One peptide selected by phage display was found to inhibit pancreatic lipase.


See also

*
Orlistat Orlistat, sold under the brand name Xenical among others, is a medication used to treat obesity. Its primary function is preventing the absorption of fats from the human diet by acting as a lipase inhibitor, thereby reducing caloric intake. It ...
(a pancreatic lipase inhibitor marketed as an anti-
obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
medication)


References


Further reading

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