Intro to Pharm and Tox Topics   

Lipases and IP3

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).

Hey! DON'T PEEK!!! Finish the questions fist!

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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