Metabolism 34

Front 1

What is Phosphatidylinositol (PIP2) hydrolyzed/degraded by and what is released?

Back 1

- PI-Phospholipase C (PI-PLC)
- DAG and IP3 are released (secondary messengers)
- IP3 releases intracellular stores of Ca

Front 2

What do DAG and Ca activate? What does this product do?

Back 2

- Calcium-Dependent Protein Kinase C (PKC)
- Phosphorylates multiple intracellular proteins

Front 3

How is DAG recycled back into PIP2?

Back 3

- DAG phosphorylated by ATP
- Produces Phosphatidic Acid
- CTP added to create CDP- Diglyceride
- Inositol added to create PI
- PI phosphorylated twice to create PIP2

Front 4

What are the major and minor pathways to liberate Arachindonic Acid from Membrane Phospholipid?

Back 4

Major:
- Stimulus binds to receptor
- PLA2, activated with Ca, modifies Phosphatidylcholine to Arachindonic Acid

Minor
- Stimulus binds to receptor
- PLC modifies Phosphatidylinositol bisphosphate to DAG
- DAG lipase creates Arachidonic Acid and Monoacylglycerol
- Monoacylglycerol lipase modifies monoacylglycerol to Aranchindonic Acid

Front 5

What are Cyclooxygenase's (COX) 2 Activities?

Back 5

Cyclooxygenase Activity: adds O2
Peroxidase Activity (synthesizes PGH2)

Front 6

What are Eicosanoids?

Back 6

Family of oxygenated arachidonic acid derivatives that interact with specific receptors to amplify/propagate flow of biological information

Front 7

Pathway to synthesize Prostacyclin (PGI2) from Arachindonic Acid

Back 7

- Add COX (O2 activity) to Arachidonic Acid
- PGG2
- Add COX (peroxidase activity) to PGG2
- PGH2
- Add PGI synthase to PGH2
- Prostacyclin

Front 8

Pathway to synthesize Thromboxane (TXA2) from Arachindonic Acid

Back 8

- Add COX (O2 activity) to Arachidonic Acid
- PGG2
- Add COX (peroxidase activity) to PGG2
- PGH2
- Add Thromboxane synthase to PGH2
- Thromboxane

Front 9

What does Prostacyclin (PGI2) do?

Back 9

- produced by endothelial cells (as is PGE2)
- increases vasodilation and decreases platelet aggregation

Front 10

What does Thromboxane (TXA2) do?

Back 10

- produced by platelets
- increases vasoconstriction and platelet aggregation

Front 11

NSAIDS
- Activity of Aspirin

Back 11

- Inhibits platelet COX 1 (prevents platelet aggregation, TXA2)
- creates irreversible covalent bond by acetylation, so COX is a dead end product

Front 12

NSAIDS
- Activity of Ibuprofen

Back 12

- Inhibits the binding of Arachidonic Acid to COX 1 and II (the O2 activity)
- competitive inhibition, thus reversible
- Celebrex/Vioxx works same way

Front 13

Activity of Acetominophen (not an NSAID)

Back 13

- Inhibits COX by acting on CNS
- Rapidly degraded, so not an anti-inflammatory

Front 14

NSAID uses and drawbacks

Back 14

- Treats inflammation and pain
- May cause ulcers

Front 15

Purpose of COX I and II in GI tract

Back 15

- mediate the secretion of bicarbonate and mucous

Front 16

Low doses of Aspirin

Back 16

- Inhibits the platelets from making thromboxane (doesn't effect endothelial cells)
- Less Thromboxane but high PIP2
- Increases platelet turnover and prevents MI

Front 17

PIP2 vs TXA2

Back 17

- Antagonistic properties regarding aggregation of platelets and vascular tone
- important in hemostatic response and atherosclerosis

Front 18

Synthetic Pathway for Leukotrienes

Back 18

- 5-Lipoxygenase modifies Arachidonic Acid into 5-HPETE
- 5-HPETE reduced to 5-HETE
-5-HETE to LTA4
- With addition of glutathione residue to LTA4 it breaks into LTC4 and LTB4
- LTC4 can break into its derivatives LTD4 and LTE4

Front 19

What are the Peptidoleukotrienes?

Back 19

LTC4
LTD4
LTE4

Front 20

What does LTB4 do in anaphylaxis?

Back 20

- Increases vascular permeability (swelling) and T-cell proliferation (inflammation), etc

Front 21

What does LTC4 and LTD4 do in anaphylaxis?

Back 21

- Increases bronchoconstriction and vascular permeability

Front 22

What biological function do leukotrienes (LT) participate in?

Back 22

anaphylaxis