[khanar]

In an animal model of myocardial ischemia, morphological and biochemical changes of the myocardial cells are studied after ligation of a branch of the coronary artery. Degredation of lipid bilayers and cytoskeletal proteins occurs following activation of intracellular phospholipase A2 and proteases. An increase in which of the following is most directly responsible for activation of those enzymes?

A- Calcium ion concentration
B- Creatinine kinase activity
C- Endonuclease activity
D- Sodium ion concentration
E- Water content

 

[ath.pantelis]

coronary ligation --> no O2 supply to myocardial cells --> no aerobic respiration --> insufficiency of ATP --> no functioning of the Sarcoplasmic Reticulum Ca2+ ATPase (SERCA) --> high concentration of Ca2+ in the cytoplasm --> activation of Phospholipase A2. So, the correct answer is A.

By the way, I would like to take advantage of the reference to SERCA and indicate that phospholamban, an inhibitor of SERCA, is being studied as a potential target in the therapeutics of Congestive Heart Failure.

 

[khanar]

What about phospholipase C

Dear ath,

Thank you for the great explanation. But would you please tell me what things that we should look for to differentiate phospholipase A2 and phospholipase C, am really confused here.

 

[ath.pantelis]

Thank you for your support, Dr. JAREDR!

This a common area of confusion, but it actually is simple (I also had this problem when I was studying for Step 1!!!). Phospholipase C is related to the signal transduction pathway of G-proteins. Thus, PLC is found on the inner side of the cell membrane bilayer and the molecules that activate it have first to interact with a receptor coupled to a G-protein, and more specifically through the Gq pathway (i.e. a1 adrenergic, M1/3/5 muscarinic, 5HT2 serotonergic, H1 histaminic, V1 of ADH).

Gq proteins activate phospholipase C (PLC), which in turn produces diacyl-glycerol (DAG) & inositol triphosphate + calcium (IP3 & Ca2+); DAG & Ca2+ activate protein kinase C (PKC). [--> this is a copy-paste mnemonic from my personal notes for Step 1: C(ue)-(PL)C-C(a2+)-(PK)C].

However, in the present case we have neither a molecule activating the Gq signaling pathway, nor a reference to PLC. On the contrary, the triggering event is the arrest of O2 & energy supply to the myocardial cell, due to blockade of the blood supply. In other words, we have phenomena similar to those observed in the context of rigor mortis. The hallmark of cell death is the release of calcium in the intracellular compartment, because the mechanism that is responsible to put Ca2+ back inside the sarcoplasmic reticulum has been ablated.

I hope this has been made clear!

 

[Seetal]

coronary ligation --> no O2 supply to myocardial cells --> no aerobic respiration --> insufficiency of ATP --> no functioning of the Sarcoplasmic Reticulum Ca2+ ATPase (SERCA) --> high concentration of Ca2+ in the cytoplasm --> activation of Phospholipase A2. So, the correct answer is A.

By the way, I would like to take advantage of the reference to SERCA and indicate that phospholamban, an inhibitor of SERCA, is being studied as a potential target in the therapeutics of Congestive Heart Failure.

wow so simply put. i love it! thanks dude.