UPSC MainsZOOLOGY-PAPER-II201715 Marks
Q25.

Give the structure of cyclic AMP and discuss its role as a second messenger by giving suitable examples.

How to Approach

This question requires a detailed understanding of cyclic AMP (cAMP) – its chemical structure and its function as a second messenger in cellular signaling. The answer should begin with defining cAMP, then illustrating its structure, and finally explaining its role with specific examples of signaling pathways. Focus on how cAMP mediates the effects of hormones and neurotransmitters. A clear, step-by-step explanation of the signaling cascade is crucial.

Model Answer

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Introduction

Cyclic adenosine monophosphate (cAMP) is a crucial intracellular signaling molecule, often referred to as a ‘second messenger’. It plays a pivotal role in mediating the effects of numerous hormones and neurotransmitters, translating extracellular signals into intracellular responses. Discovered in the 1960s, cAMP’s significance lies in its ability to amplify signals and regulate a wide array of cellular processes, including metabolism, gene expression, and ion channel activity. Understanding its structure and mechanism of action is fundamental to comprehending cellular communication and its dysregulation in various diseases.

Structure of Cyclic AMP

cAMP is a derivative of adenosine triphosphate (ATP). It is formed by the removal of pyrophosphate from ATP, resulting in a cyclic phosphate group attached to the ribose sugar. The chemical formula of cAMP is C10H16N5O5P. Its structure consists of a ribose ring, adenine base, and a phosphate group forming a cyclic bond with the 5' carbon of the ribose. This cyclic structure is key to its function, making it more resistant to degradation by phosphodiesterases compared to ATP.

cAMP as a Second Messenger: Mechanism of Action

The term "second messenger" signifies that cAMP acts as an intermediary between an extracellular signal (the "first messenger," like a hormone) and a cellular response. The process unfolds as follows:

  1. Hormone/Neurotransmitter Binding: An extracellular signaling molecule (e.g., epinephrine, glucagon) binds to a G protein-coupled receptor (GPCR) on the cell surface.
  2. G Protein Activation: This binding activates a G protein, causing it to exchange GDP for GTP.
  3. Adenylate Cyclase Activation: The activated G protein stimulates the enzyme adenylate cyclase.
  4. cAMP Production: Adenylate cyclase catalyzes the conversion of ATP to cAMP.
  5. Protein Kinase A (PKA) Activation: cAMP binds to the regulatory subunits of protein kinase A (PKA), causing them to dissociate from the catalytic subunits.
  6. Phosphorylation Cascade: The activated catalytic subunits of PKA phosphorylate specific target proteins, leading to a cellular response.
  7. Signal Termination: cAMP is degraded by phosphodiesterases (PDEs), terminating the signal.

Examples of cAMP’s Role as a Second Messenger

1. Epinephrine and Glycogen Breakdown

When epinephrine (adrenaline) binds to β-adrenergic receptors in liver and muscle cells, it initiates the cAMP signaling pathway. This leads to the activation of PKA, which phosphorylates and activates glycogen phosphorylase. Glycogen phosphorylase then breaks down glycogen into glucose, providing energy for the "fight or flight" response. This is a classic example of how cAMP mediates hormonal effects on metabolism.

2. Glucagon and Glucose Production

Glucagon, a hormone released by the pancreas, also utilizes the cAMP pathway in the liver. Binding of glucagon to its receptor activates adenylate cyclase, increasing cAMP levels. PKA activation subsequently promotes gluconeogenesis (glucose synthesis) and inhibits glycogen synthesis, raising blood glucose levels.

3. Regulation of Heart Rate

Epinephrine, acting through β-adrenergic receptors in the heart, increases cAMP levels. This activates PKA, which phosphorylates ion channels, increasing heart rate and contractility. This demonstrates cAMP’s role in regulating cardiovascular function.

4. Olfactory Signal Transduction

In olfactory neurons, odorant binding to receptors activates adenylate cyclase, increasing cAMP levels. This opens cyclic nucleotide-gated ion channels, leading to depolarization and signal transmission to the brain. This illustrates cAMP’s role in sensory perception.

Regulation of cAMP Levels

The concentration of cAMP within the cell is tightly regulated. Adenylate cyclase activity determines the rate of cAMP synthesis, while phosphodiesterases (PDEs) control its degradation. Different isoforms of PDEs exist, exhibiting varying substrate specificities and sensitivities to regulation, allowing for fine-tuning of cAMP signaling in different tissues and cellular compartments.

Conclusion

Cyclic AMP is a remarkably versatile second messenger, orchestrating a diverse range of cellular responses to extracellular signals. Its role in mediating hormonal and neurotransmitter effects is fundamental to physiological processes like metabolism, cardiovascular function, and sensory perception. Understanding the cAMP signaling pathway is crucial for comprehending both normal cellular function and the pathogenesis of various diseases, offering potential therapeutic targets for intervention. Further research continues to unveil the intricate complexities of cAMP signaling and its impact on cellular regulation.

Answer Length

This is a comprehensive model answer for learning purposes and may exceed the word limit. In the exam, always adhere to the prescribed word count.

Topics Covered

BiologyBiochemistryCell SignalingSecond MessengersHormone Action