Lipases are enzymes that hydrolyze triacylglycerols or diacylglycerols to liberate various second messengers ad fatty acids:
There are at least four kinds of lipases: phospholipases C, D and A2, and diacylglycerol lipase.
Phospholipase C (PLC) generates two intracellular messengers: inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), from the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2):
PLC can also hydrolyze phosphatidylserine and phosphatidylethanolamine.
Phospholipase D (PLD) catalyzes the hydrolysis of phospholipids at a terminal phosphodiester bond, for example phosphatidylcholine, producing phosphatidic acid (PA).
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Phospholipase A2 (PLA2) liberates arachidonic acid by cleaving the second position of glycerol:
PLA2
also liberates other fatty acids, but arachidonic is the most important. A summary
of cleavage sites for phospholipases on a phospholipid follows:
Diacylglycerol lipase is a catabolic enzyme of diacylglycerol which forms monoacylglycerol, most of the time cleaving at the second position, and usually liberating arachidonic acid:
There are at least 10 mammalian isoforms of PLC, divided into three types: beta, gamma and delta. Two regions of high homology between the isozymes contain the catalytic activity.
PLCbeta is usually activated by the alpha subunit of a Gq class of heterotrimeric G-protein. Some isozymes can be activated by the beta/gamma complex.
PLCgama is activated by tyrosine phosphorylation. Several polypeptide growth factors like platelet-derived growth factor, nerve growth factor and epidermal growth factor activate PLCgama by phosphorylation of tyrosine kinase receptors.
As a second messenger, IP3 liberated by PLC diffuses into the cytoplasm and binds intracellular receptors that release Ca2+. There are at least four different IP3 receptor genes (splice variants?). The receptor has three domains: an N-terminus IP3 binding domain, a regulatory domain with ATP binding and phosphorylation sites, and a six transmembrane region. IP3 is catabolized by phosphatases into inositol, which can be recycled into the membrane phospholipids.
Continue to "Diacylglycerol
and PKC" or take a quiz: [Q1] [Q2]
[Q3] [Q4].
Need more practice? Answer the review questions below (after sponsor).
1- What are lipases?
2- List 4 classes of lipases.
3- What is the activity of phospholipase C?
4- What is the activity of phospholipase D?
5- What is the activity of phospholipase A2?
6- What is the activity of diacylglycerol lipase?
7- List 3 types of phospholipase C
8- What is the common structure between phospholipase isozymes?
9- How is PLCbeta activated?
10- How is PLCgamma activated?
11- What is the activity of IP3?
12- What is the structure of the IP3 receptor?
13- How is IP3 catabolized?
Continue scrolling to answers below (after sponsor).
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Answers:
1- What are lipases?
Enzymes that hydrolyze triacylglycerols or diacylglycerols to liberate various
second messengers and fatty acids.
2- List 4 classes of lipases.
phospholipase A2
phospholipase C
phospholipase D
diacylglycerol lipase
3- What is the activity of phospholipase
C?
Generates inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) from the
membrane lipid phosphatidylinositol 4,5 bisphosphate (PIP2). It can also hydrolyze
phosphatidylserine and phosphatidylethanolamine.
4- What is the activity of phospholipase
D?
Catalyzes the hydrolysis of phospholipids at a terminal phosphodiester bond,
producing phosphatidic acid.
5- What is the activity of phospholipase
A2?
Liberates fatty acids, especially arachidonic acid, by cleaving at the second
position of glycerol.
6- What is the activity of diacylglycerol
lipase?
Catabolic enzyme of diacylglycerol, forms a monoacylglycerol, most of the time
by cleaving at the second position. Usually liberates arachidonic acid.
7- List 3 types of phospholipase
C
phospholipase C beta (PLCbeta)
phospholipase C gamma (PLCgamma)
phospholipase C delta (PLCdelta)
8- What is the common structure
between phospholipase isozymes?
Two regions of high homology contain the catalytic activity.
9- How is PLCbeta
activated?
Usually by the alpha subunit of a Gq class of heterotrimeric
G-protein, but some can be activated by the beta/gamma complex.
10- How is PLCgamma
activated?
By tyrosine phosphorylation catalyzed by several polypeptide growth factors
like platelet-derived growth factor, nerve growth factor and epidermal growth
factor
11- What is the activity of IP3?
It diffuses into the cytoplasm
and binds intracellular receptors that release calcium
12- What is the structure of the
IP3 receptor?
Has three domains: an IP3 binding domain at the N-terminus, a regulatory domain
with ATP binding and phosphorylation sites, and a six transmembrane region.
13- How is IP3
catabolized?
By phosphatases into inositol, which can be recycled into the membrane phospholipids.
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