lipase, any enzyme capable of degrading lipid molecules. The bulk of dietary lipids are a class called triacylglycerols and are attacked by lipases to yield simple fatty acids and glycerol, molecules which can permeate the membranes of the stomach and small intestine for use by the body. Gastric lipase, secreted by the stomach lining, has a pH value for optimal activity around neutrality and would appear, therefore, to be essentially inactive in the strongly acid environment of the stomach. It is suggested that this enzyme is more important for infant digestion since the gastric pH in infancy is much less acid than later in life. Most lipid digestion in the adult occurs in the upper loop of the small intestine and is accomplished by a lipase secreted by the pancreas. Phospholipases are the enzymes that degrade phospholipids.

A lipase is a water-soluble enzyme that catalyzes the hydrolysis of ester bonds in water–insoluble, lipid substrates. Lipases thus comprise a subclass of the esterases.

Lipases perform essential roles in the digestion, transport and processing of dietary lipids (e.g. triglycerides, fats, oils) in most- if not all- living organisms. Genes encoding lipases are even present in certain viruses.

Function

Most lipases act at a specific position on the glycerol backbone of a lipid substrate (A₁, A₂ or A₃).

In the example of human pancreatic lipase (HPL), which is the main enzyme responsible for breaking down fats in the human digestive system, a lipase acts to convert triglyceride substrates found in oils from food to monoglycerides and free fatty acids.

Myriad of other lipase activities exist in nature, especially when the phospholipases and sphingomyelinases are considered.

Structure

While a diverse array of genetically distinct lipase enzymes are found in nature, and represent several types of protein folds and catalytic mechanisms, most are built on an alpha/beta hydrolase fold (see image) and employ a chymotrypsin-like hydrolysis mechanism involving a serine nucleophile, an acid residue (usually aspartic acid), and a histidine.

Physiological distribution

Lipases are involved in diverse biological processes ranging from routine metabolism of dietary triglycerides to cell signaling and inflammation. Thus, some lipase activities are confined to specific compartments within cells while others work in extracellular spaces.

• In the example of lysosomal lipase, the enzyme is confined within an organelle called the lysosome.
• Other lipase enzymes, such as pancreatic lipases, are secreted into extracellular spaces where they serve to process dietary lipids into more simple forms that can be more easily absorbed and transported throughout the body.
• Fungi and bacteria may secrete lipases to facilitate nutrient absorption from the external medium (or in examples of pathogenic microbes, to promote invasion of a new host).
• Certain wasp and bee venoms contain phospholipases that enhance the "biological payload" of injury and inflammation delivered by a sting.
• As biological membranes are integral to living cells and are largely composed of phospholipids, lipases play important roles in cell biology.

Lipases of humans

The main lipases of the human digestive system are human pancreatic lipase (HPL) and pancreatic lipase related protein 2 (PLRP2), which are secreted by the pancreas. Humans also have several other related enzymes, including hepatic lipase (HL), endothelial lipase, and lipoprotein lipase. Not all of these lipases function in the gut (see table).

Name	Gene	Location	Description	Disorder
pancreatic lipase		digestive juice	In order to exhibit optimal enzyme activity in the gut lumen, HPL requires another protein, colipase, which is also secreted by the pancreas.	-
lysosomal lipase		interior space of organelle: lysosome	Also referred to as lysosomal acid lipase (LAL or LIPA) or acid cholesteryl ester hydrolase	Cholesteryl ester storage disease (CESD) and Wolman disease are both caused by mutations in the gene encoding lysosomal lipase.
hepatic lipase		endothelium	Hepatic lipase acts on the remaining lipids carried on lipoproteins in the blood to regenerate LDL (low density lipoprotein).	-
lipoprotein lipase	or "LIPD"	endothelium	Lipoprotein lipase functions in the blood to act on triacylglycerides carried on VLDL (very low density lipoprotein) so that cells can take up the freed fatty acids.	Lipoprotein lipase deficiency is caused by mutations in the gene encoding lipoprotein lipase.
hormone-sensitive lipase		intracellular	-	-
gastric lipase		digestive juice	Functions in the infant at a near-neutral pH to aid in the digestion of lipids	-
endothelial lipase		endothelium	-	-
pancreatic lipase related protein 2	or "PLRP2" -	digestive juice	-	-
pancreatic lipase related protein 1	or "PLRP1"	digestive juice	Pancreatic lipase related protein 1 is very similar to PLRP2 and HPL by amino acid sequence (all three genes probably arose via gene duplication of a single ancestral pancreatic lipase gene). However, PLRP1 is devoid of detectable lipase activity and its function remains unknown, even though it is conserved in other mammals.	-
lingual lipase	?	digestive juice	-	-

Other lipases include , , , , , , , , , and .

There also are a diverse array of phospholipases, but these are not always classified with the other lipases.

Industrial Uses

Lipases from fungi and bacteria serve important roles in human practices as ancient as yogurt and cheese fermentation. However, lipases are also being exploited as cheap and versatile catalysts to degrade lipids in more modern applications. For instance, a biotechnology company has brought recombinant lipase enzymes to market for use in applications such as baking, laundry detergents and even as biocatalysts in alternative energy strategies to convert vegetable oil into fuel.

Additional images

References

External links

• Selective Inhibitors of Monoacylglycerol Lipase as a Treatment for Neurological Disorders 2004-637
• - Phospholipases A2
• - Outer membrane phospholipase A
• - Cytosolic phospholipase A2 and patatin
• - Bacterial and mammalian phospolipases C
• - α-toxin (a bacterial phospholipase C)

See also

• Triglyceride lipase
• Phospholipase A
• Phospholipase C
• Alpha toxin
• Peripheral membrane proteins