Phospholipase A2 (PLA2) liberates arachidonic acid by cleaving at the second position of glycerol. It also liberates other fatty acids but arachidonic is the most important:
When PLA2 hydrolyses phosphatidic acid, lysophosphatidic acid is formed:
Lysophosphatidic acid can act as a first messenger by leaving the cell and activating EDG receptors (a G-protein coupled receptor).
Some PLA2 isozymes are soluble but the most important are mebrane-bound. They are directly activated by Ca2+ and PKC, and indirectly activated by PLC trough PKCa nd Ca2+.
PLC
PIP2
IP3
IP3 receptor
Ca2+
PLA2
PLC
DAG PKC
PLA2
PLA2 isbloked by steroids.
There are four possible fates of arachidonic acid:
Ecosanoids, the metabolic products of arachidonic acid, act as paracrine and autocrine hormoes that activate other transduction cascades by activation of G-protein coupled receptors. They are not stored but synthesized on demand. In some instances may be second messengers. They are not stored but synthesized on demand. In some intances, may act as second messengers.
Arachidonic acid is metabolized by cyclooxygenases into prostaglandings and thromboxanes. There are at least two cyclooxygenase isoforms: constitutive (COX1) and inducible (COX2). Both isoforms are irreversibly inhibited by aspirin. COX2 selective inhhibitors have been developed.
Lipoxygenases make hydroperoxyecosatetraenoic acids (HPETES) from arachidoniic acid, then reduce them to hydroecosatetraenoic acids (HETS). 12'lipoxygenase is found mostly in the central nervous system and its product is thought to be a second messenger. Lypoxygenases require Ca2+, ATP and hydroperoxy acid.
Arachidonic acid is metabolized by P450 into epoxyeicosatrienoic acids (EETS) which regulate vasodilation and blood pressure.
Continue to "Kinases
and Phosphatases" or take a quiz: [Q1]
[Q2] [Q3] [Q4].
Need more practice? Answer the review questions below (after sponsor).
1- How is lysophosphatidic acid formed?
2- What is the activity of lysophospatidic acid?
3- How is PLA2 blocked?
4- How is PLA2 activated
5- List 4 fates of arachidonic acid.
6- What are ecosanoids?
7- What is the activity of ecosanoids?
8- List 2 cyclooxygenase isozymes.
9- List 2 cyclooxygenase inhibitors andtheir activity.
10- What is the activity opf lipoxygenases?
11- Where is 12'lipoxigenase founds and what is its activity?
12- What is the activity of cyclooxygenases?
13- What is the activity of P450 on arachidonic acid?
Continue scrolling to answers below (after sponsor).
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Answers:
1- How is lysophosphatidic acid
formed?
By hydrolysis of phosphatidic acid by PLA2.
2- What is the activity of lysophospatidic
acid?
Acts a a first messenger by leaving the cell and activating EDG receptors (a
G-protein coupled receptor).
3- How is PLA2
blocked?
By steroids.
4- How is PLA2
activated
Directly by PKC and Ca2+, indirectly by PLC through DAG-->PKC and IP3-->Ca2+.
5- List 4 fates of arachidonic
acid.
reincorporatyed into plasma membrane
metabolyzed by cyclooxygenase
mtabolized by lipoxygenases
metabolized by cytochrome P450
6- What are ecosanoids?
Metabolic products of arachidonic acid: prostaglandings, thremboxanes and leukotrienes.
They are not stored but syntesized on demend.
7- What is the activity of ecosanoids?
Act as paracrine and autocrine hormones that initiate transduction cascades
by activating G-protein coupled receptors. In some instances may be second mesengers.
8- List 2 cyclooxygenase isozymes.
constitutive, COX1
inducible (COX2)
9- List 2 cyclooxygenase inhibitors
andtheir activity.
aspirin irreversibly inhibits both COX1 and COX 2
COX2 selective inhibitors
10- What is the activity opf lipoxygenases?
Make HPETES from arahidonic acid, the reduces them (?) to HETES, the precursors
of leukotrienes. They require Ca2+, ATPase and hydroperoxy acid.
11- Where is 12'lipoxigenase founds
and what is its activity?
Mostly in the central nervous system and its product is thought to be a second
messenger.
12- What is the activity of cyclooxygenases?
Metabolize arachidonic acid into prstaglandings and thromboxanes.
13- What is the activity of P450
on arachidonic acid?
It is metabolized to EETS, which regulates vasodilation and blood pressure.
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