Question

Manic-depression may be caused by overactivity of certain central nervous system cells, perhaps caused by an overstimulation of the phosphatidylinositol (PI) cycle. Lithium has been used in the treatment of this condition as it slows the PI cycle despite continued stimulation and cells may become less sensitive to these stimuli. Li \(^{+}\) may have two functions: inhibition of the phosphatase that dephosphorylates \(\mathrm{IP}_{3}\) and direct interference with the function of \(\mathrm{G}\) proteins. Which of the following statements concerning G proteins is correct? A. G proteins bind the appropriate hormone at the cell surface. B. G proteins interact with cytoplasmic receptors. C. G proteins are second messengers. D. G protein causes the regulatory subunits of the protein kinase to dissociate from the catalytic subunits. E. activated G protein may cither activate or inhibit the production of second messenger.

Short answer

Answer: Activated G protein may either activate or inhibit the production of a second messenger.

Step-by-step solution

Introduction to G proteins

G proteins are proteins that transmit signals from various stimuli outside the cell to the cell's interior, which eventually leads to a response within the cell. They act like a molecular switch that is turned 'on' or 'off' by specific outside stimuli. G proteins interact with cell surface receptors and intracellular effector proteins.

Evaluating statements

Let's go through each statement and evaluate their correctness. A. G proteins bind the appropriate hormone at the cell surface. - Incorrect. It is the cell surface receptors that bind to the hormone or ligand, not the G proteins. G proteins interact with these receptors. B. G proteins interact with cytoplasmic receptors. - Incorrect. G proteins interact with cell surface receptors, not cytoplasmic ones. C. G proteins are second messengers. - Incorrect. G proteins are not second messengers. They are proteins that help transmit the signal from the cell surface receptor to the second messengers, such as cAMP or IP3, which then relay the signal within the cell. D. G protein causes the regulatory subunits of protein kinase to dissociate from the catalytic subunits. - Incorrect. G proteins do not directly cause the dissociation of regulatory and catalytic subunits of protein kinases. They transmit signals to other effector proteins, which can then regulate protein kinases. E. Activated G protein may either activate or inhibit the production of a second messenger. - Correct. Depending on the specific pathway and the type of G protein involved, activated G proteins can stimulate or inhibit the production of second messengers like cAMP or IP3.

Conclusion

From the analysis of the different statements proposed, the correct statement concerning G proteins is: E. Activated G protein may either activate or inhibit the production of a second messenger.

Key concepts

Signal Transduction

Signal transduction refers to the process by which a cell responds to external stimuli, such as hormones, neurotransmitters, or growth factors. It involves the conversion of a signal from outside the cell into a functional response within the cell. This is a critical mechanism in ensuring that cells can adapt and react to their changing environment.

At the heart of signal transduction are receptor proteins located on the cell surface. These receptors detect specific molecules and trigger a complex cascade of events inside the cell. G proteins play a key role in this process. They act as molecular switches that connect the activation of cell surface receptors to the activation of internal signaling pathways. Once activated by a receptor, G proteins can influence a variety of cellular processes, including gene expression, cell growth, and metabolism.

Understanding signal transduction pathways is essential for comprehension of how cells maintain internal balance in response to external changes, and it is crucial for the development of medications that treat conditions like manic-depression.

Phosphatidylinositol (PI) Cycle

The phosphatidylinositol (PI) cycle is an essential signal transduction pathway that is involved in various cellular processes. It utilizes a group of phospholipids found in cell membranes as signaling molecules. Specifically, the PI cycle involves the phosphorylation and dephosphorylation of phosphatidylinositol bisphosphate (PIP2), producing the second messengers inositol trisphosphate (IP3) and diacylglycerol (DAG).

IP3 facilitates the release of calcium ions from intracellular stores, which participate in numerous cellular functions including muscle contraction, neurotransmitter release, and cell growth. DAG, in conjunction with calcium ions, activates protein kinase C (PKC), which further transduces the signal by phosphorylating other proteins. The PI cycle's contribution to cellular signal transduction is crucial, and when dysregulated, it can be involved in the pathogenesis of disorders, including manic-depression. The treatment with lithium in such conditions can affect this cycle by inhibiting enzymes involved in the PI cycle, thereby modulating the cell's response to continuous stimulation.

Manic-Depression and Lithium Treatment

Manic-depression, also known as bipolar disorder, is a psychiatric condition characterized by alternating periods of mania (elevated mood or irritability) and depression (low mood). While the exact cause of manic-depression remains unclear, research suggests that it may involve disruptions in various neurotransmitter systems and signal transduction pathways, including the PI cycle.

Lithium has been a cornerstone in the treatment of manic-depression for decades. It is thought to exert its therapeutic effects by stabilizing mood fluctuations. Lithium interacts with the PI cycle by inhibiting the recycling of inositol, reducing the availability of inositol trisphosphate (IP3), and possibly influencing G protein function. By doing so, lithium treatment can dampen the overactivity of certain neural pathways that are implicated in the extremes of mood associated with bipolar disorder. Despite its effectiveness, the complete mechanism of action of lithium still invites further research.

Second Messengers

Second messengers are small molecules that relay signals received by cell surface receptors to target molecules inside the cell, thus initiating physiological changes. These molecules form the link between the reception of the external signal at the receptor and the internal actions that will occur as a response.

Common second messengers include cyclic AMP (cAMP), inositol trisphosphate (IP3), diacylglycerol (DAG), and calcium ions (Ca2+). For instance, cAMP is produced from ATP by an enzyme called adenylyl cyclase, and it can activate protein kinases, which phosphorylate other proteins to regulate their function. On the other hand, IP3 is generated by the action of phospholipase C on phosphatidylinositol bisphosphate (PIP2) as part of the PI cycle, leading to an increase in intracellular calcium levels.

Second messengers are integral to the cell's ability to respond to a multitude of signals with a variety of responses and are pivotal in many biological processes, including energy metabolism, cell proliferation, and neuronal functioning.