Physiology 534 Exam Iv: Eicosanoid Hormones

Front 1

What is the general scheme on how eicosanoids are produced?

Back 1

Stimulus: thrombin-->receptor on PM-->activates phospholipase A2-->releases FA from membrane-->-->-->eicosanoids

Front 2

What 3 molecules are known as the eicosanoids?

Back 2

1. Prostaglandins
2. Thromboxanes
3. Leukotriens

Front 3

Thromboxanes

Back 3

Stimulus: thrombin
Target: Platelet cells
Response: Aggregation via thromboxane

Front 4

Leukotrienes

Back 4

Stimulus: Antigen Ig-E
Target: Mast cells
Response: anaphylactic shock via leukotriene

Front 5

Prostaglandins

Back 5

Stimulus: pyrogens
Target: hypothalmus cells
Response: Fever via Prostaglandins

Front 6

Characteristics of eicosanoids?

Back 6

1. All derived from FA, 20 C long
2. Made on many cell types, act on many tissues
3. Bind to specific receptors
4. Many biological responses
5. Act on nearby cells (autocrine/paracrine)
6. Short-lived & very potent

Front 7

Are eicosanoids endogenous?

Back 7

No, need to ingest because body can only insert double bonds up to carbon 9.

Front 8

How is linoleic acid a precursor to eicosanoids?

Back 8

diet-->linoleic acid-->desaturation-->elongation-->desaturation-->arachidonyl CoA-->inserted into membrane phospholipids & becomes a starting point for eicosanoid synthesis.

Front 9

Synthesis of eicosanoids

Back 9

Membrane phospholipids taken from membrane via phosholipase A2 enzyme-->arachidonate

Now, there are 2 pathways: lipooxygenase & cyclooxygenase pathway

Front 10

Lipooxygenase Pathway

Back 10

Arachidonate-->HETE-->Leukotrienes

Front 11

Cyclooxygenase Pathway

Back 11

Arachidonate-->prostanoids-->prostaglandins & thromboxane

Front 12

What are the + and - regulators of phospholipase A2 enzyme?

Back 12

+ stimulated by thrombin
- regulated by anti-inflammatory corticosteroids (cortisone)

Front 13

What does Asprin do?

Back 13

Asprine is a negative regulator of PGH synthase of the cyclooxygenase pathway-->more arachidonate-->more lipooxygenase pathway-->inc. leukotrienes

Front 14

Characteristics of Leukotrienes

Back 14

-20C FA
-3 conjugated double bonds
-isolated from leukocytes

Front 15

Characteristics of prostaglandins

Back 15

-20 C FA
-5 C ring
-Isolated in prostate

Front 16

Characteristics of thromboxane

Back 16

-20C FA
-6 member ether ring
-Isolated from thrombocytes

Front 17

What is the common intermediate in the cyclooxygenase pathway?

Back 17

PGH2

Front 18

PGH2 with the enzyme Prostacyclin synthase in the cox pathway produces?

Back 18

PGI2

Endothelial cells express prostacyclin synthase

Front 19

PGH2 with enzyme thromboxane synthase in the cox pathway produces?

Back 19

TXA2

from platelets

Front 20

Physiological effects of Leukotrienes

Back 20

-muscle contractant of non-vascular smooth muscle
-constrict small airways of lungs
-slow reacting substances of anaphylaxis (not already made or stored)
-main culprit: anaphylactic shock

Front 21

Production of PGI2 & TXA2?
PGI2 & TXA2 have antagonistic effects.

Back 21

PGI2: produced by endothelial cells

TXA2: produced by platelets

Front 22

Which (PGI2 or TXA2) is short/long-lived?

Back 22

PGI2: long-lived

TXA2: short-lived

Front 23

Which (PGI2 or TXA2) contains nuclei & protein synthesis machinery?

Back 23

PGI2: contains

TXA2: does not contain

Front 24

How does PGI2 regulate BP?

How does TXA2 regulate BP?

Back 24

Vasodilating

Vasoconstricting

Front 25

Which (PGI2 or TXA2) inhibits/promotes platelet aggregation?

Back 25

PGI2: inhbits platelet aggregation

TXA2: promotes platelet aggregation

Front 26

Physiological effects of prostaglandins?

Back 26

-Protects against excess gastric acidity "cytoprotection"
Housekeeping function

-Inducible function

Front 27

How does prostaglandins protect against excess acidity?

Back 27

it inhibits incr. cAMP production which causes inc. stomach acidity

Front 28

Inducible function of prostaglandins

Back 28

-Inducible bc PGE's induced by the outside signal (lipopolysacchride LPS)-->hypothalamus-->regulates T-->arteriolar vasodilation & inc. capillary permeability

-inflammation, edema, heat/skin redness

Front 29

What happens if we have an inhbition of phospholipase A2?

Back 29

Stop of eicosanoid production

Front 30

What happens if we have an inhbition of PGH Synthase?

Back 30

Occurs via Asprin, a NSAID, affects Cox pathway

Front 31

What does this mean when pharmacueticals say, "drug A is easier on the stomach than drug B?"

Back 31

There are 2 isozymes for PGH Synthase

Want to find drugs that will inhbit inflammatory respones cox 2 without affecting housekeeping functions of cox 1

Front 32

Cox 1

Back 32

-Channel narrower therefore bulky molecules cannot pass

fxn: housekeeping, GI integrity, vascular homeostatis, "constitutive"

Front 33

Cox 2

Back 33

channel larger

fxn: inflammatory response, macrophages

Front 34

Ibuprofin

Back 34

cox 1 = cox 2

Front 35

Indomethacin

Back 35

cox 1 > cox 2

Front 36

6-MNA

Back 36

Cox 1 < cox 2

Front 37

Aspirin overdose

Back 37

Conjugation system is overwhelmed leading to hepatocellular damage

Front 38

Aspirin overdose leads to clear evidence of hepatocellular damage. What are the evidence?

Back 38

1. failure to maintain blood glucose level
2. poor conjugation of bilirubin for excretion
3. bile acids for absorption and transport of vitamin k (prothrombin time lower)
4. Leakage of liver enzymes in plasma