Lipase

A Lipase is a water-soluble enzyme that catalyzes the hydrolysis of ester bonds in waterinsoluble, lipid substrates. 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 convert triglyceride substrates found in oils from food to monoglycerides and free fatty acids. A myriad of other lipase activities exist in nature, especially when the phospholipases and sphingomyelinases are considered.

Lipases are ubiquitous throughout living organisms, and genes encoding lipases are even present in certain viruses. While a diverse array of genetically distinct lipase enzymes are found in nature, and represent distinct types of protein folds [1] and catalytic mechanisms, most are built on a alpha/beta hydrolase fold (see image below) and employ a chymotrypsin-like hydrolysis mechanism involving a serine nucleophile, an acid residue (usually aspartic acid), and a histidine.

Some lipases work within the interior spaces of living cells to degrade lipids. In the example of lysosomal lipase, the enzyme is confined within an organelle called the lysosome. Other lipase enzymes, such as pancreatic lipases, are found in the spaces outside of cells and have roles in the metabolism, absorption and transport of lipids throughout the body. As biological membranes are integral to living cells and are largely composed of phospholipids, lipases play important roles in cell biology. Furthermore, lipases are involved in diverse biological processes ranging from routine metabolism of dietary triglycerides to cell signaling and inflammation. Several different types of lipases are found in the human body, including pancreatic lipase, hepatic lipase, lysosomal lipase, hepatic lipase, gastric lipase, endothelial lipase, as well as various different phospholipases.

At least three human genetic diseases are caused by mutations in lipase genes. Lipoprotein Lipase Deficiency is caused by mutations in the gene encoding lipoprotein lipase [2]. Cholesteryl Ester Storage Disease (CESD) and Wolman Disease are both caused by mutations in the gene encoding lysosomal lipase, also referred to as lysosomal acid lipase (LAL or LIPA) or acid cholesteryl ester hydrolase [3].

Below is a computer generated image of a type of pancreatic lipase (PLRP2) from the guinea pig, it is a 3-D model from structure coordinates submitted to the Protein Data Bank from: Withers-Martinez, C., F. Carriere, R. Verger, D. Bourgeois, and C. Cambillau. 1996. A pancreatic lipase with a phospholipase A1 activity: crystal structure of a chimeric pancreatic lipase-related protein 2 from guinea pig. Structure 4:1363-74.

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