Lipase
|
A computer-generated image of a type of pancreatic lipase (PLRP2) from the guinea pig. . |
A
lipase is a
water-soluble enzyme that
catalyzes the
hydrolysis of
ester bonds in waterâ€"insoluble,
lipid substrates. Most lipases act at a specific position on the
glycerol backbone of a lipid substrate (A
1, A
2 or A
3). 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 mono
glycerides and free
fatty acids. Myriad 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 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.
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, 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 [
1].
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 [
2].
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