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NEET PG 2018 Recall Question - Nitric Oxide - Mechanism of Action - Biochemistry

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The correct answer is c. Guanylate cyclase Pathway. To understand why this is the case, it's essential to delve into the role of nitric oxide (NO) in physiological processes and how it interacts with various signaling pathways.
Nitric Oxide (NO)
Nitric oxide is a gaseous signaling molecule involved in numerous physiological and pathological processes. It is unique among signaling molecules because it is a gas and diffuses freely across cellular membranes. NO is synthesized in the body by nitric oxide synthases (NOS), which convert L-arginine into NO and L-citrulline. Once produced, NO plays critical roles in vascular regulation, neurotransmission, and immune responses. Its mechanism of action is primarily through the activation of soluble guanylate cyclase (sGC), leading to the production of cyclic guanosine monophosphate (cGMP), a second messenger involved in various cellular responses.
Answer Options Analysis
a. Adenyl Cyclase Pathway involves the conversion of ATP to cyclic AMP (cAMP) by the enzyme adenyl cyclase. cAMP is another important second messenger that regulates many different cellular processes, including metabolism and calcium channel regulation. While cAMP and its pathway are crucial in many signaling processes, they are not the primary pathway through which NO exerts its effects.
b. Phosphatidylinositol Pathway involves the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into two secondary messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), by the enzyme phospholipase C (PLC). This pathway is involved in the regulation of intracellular calcium levels and activation of protein kinase C (PKC). Though important for many signaling processes, it is not the main pathway for NO action.
c. Guanylate Cyclase Pathway is the most relevant pathway for NO action. NO activates soluble guanylate cyclase (sGC), an enzyme that converts guanosine triphosphate (GTP) into cyclic guanosine monophosphate (cGMP). cGMP acts as a second messenger in various physiological processes, such as smooth muscle relaxation, which is crucial in vasodilation and thus in controlling blood pressure. This pathway is directly activated by NO and is responsible for many of its physiological effects.
d. MAP Kinase Pathway involves a series of protein kinases that lead to the activation of mitogen-activated protein kinases (MAPKs), which regulate cell growth, differentiation, and apoptosis. While NO can influence the MAP kinase pathway indirectly, it is not the primary effector pathway for its action.
Conclusion
The Guanylate Cyclase Pathway is the most important effector pathway for the action of nitric oxide because it directly mediates the conversion of GTP to cGMP upon activation by NO. This leads to various downstream effects, including smooth muscle relaxation and vasodilation, highlighting its critical role in NO's physiological actions.
Nitric Oxide
→ Uncharged molecule is highly reactive , free radical [t1/2 - 0.1 s]
→ Also called Endothelial Derived Growth Factor
Mechanism of Action of Nitric Oxide
Step 1 - ↑ Ca
Step 2 -Liberation of NO
Step 3 -Reacts with Heme moiety of Guanylyl Cyclase
Step 4 -↑ cGMP
Step 5 -Interact with Protien Kinase (Muscle Relaxation)
Function of Action of Nitric Oxide
1. Potent Vasodialator [Involved in Erection]
2. Neurotransmitter in Brain & Peripheral Nervous System
3. Low Level of NO in Pylorospasm in Cong. Hypertrophic Pyloric Stenosis
4. Inhibits Adhesion, Activation and Aggregation of platelets
Therapeutic Use of Action of Nitric Oxide
1. Inhalation on NO in Pulmonary Hypertension
2. Treatment of Impotence [Sildenafil (-) cGMP Phosphodiesterase]
3. Glyceryl Nitrate is converted to NO in Angina Pectoris
Subtypes of Action of Nitric Oxide
nNOS
→Activated by ↑ Ca (First Identified in Neurons)
→Pyloric Stenosis Aggressive Sexual Behavior
iNOS
→ In Macrophages Independent of Ca
→Susceptible to Infections
eNOS
→Activated by ↑ Ca (First Identified in endothelial Cells)
→Elevated Mean BP

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