Question

A cell membrane constituent that transports chemotherapeutic drugs out of a target cell. (A) plasmid (B) porin (C) resistance factor (D) \(\beta\)-lactamase (E) P-glycoprotein

Short answer

The correct answer is (E) P-glycoprotein.

Step-by-step solution

Understand the Terms

Start by identifying what each term means in the context of cellular biology. Plasmids are extra-chromosomal DNA that often carry antibiotic resistance genes. Porins are proteins that form pores in cell membranes. Resistance factors are genetic elements providing resistance to antibiotics, and β-lactamase is an enzyme that deactivates β-lactam antibiotics. P-glycoprotein is a membrane protein that pumps foreign substances out of cells.

Analyze the Functionality Required

The exercise asks for a membrane constituent that actively transports chemotherapeutic drugs out of a target cell. This means it needs to be a transporter protein capable of drug efflux.

Match Functionality to Options

Evaluate each given option to see if it matches the required functionality. Plasmids, while they carry genes, do not directly transport substances themselves. Porins facilitate passive diffusion, not active transport. Resistance factors are not standalone transporters. β-lactamases are enzymes degrading antibiotics, not transporters. P-glycoprotein is known to pump drugs out of cells using ATP, matching the task description.

Select the Best Option

Having matched functions to needs, select the option that correctly describes a membrane transporter that expels drugs. In this case, P-glycoprotein fits, as it actively pumps drugs such as chemotherapeutics out of cells.

Key concepts

Cell Membrane Transport

Cell membrane transport is a fundamental process that allows cells to maintain their internal environment while interacting with external surroundings. The cell membrane, a lipid bilayer studded with proteins, acts as a barrier and a gatekeeper. This process is vital as it regulates the movement of substances in and out of a cell. There are two main types of membrane transport mechanisms: passive and active transport.

• Passive transport does not require energy and includes simple diffusion and facilitated diffusion, where substances move down their concentration gradient through channels or carriers.
• Active transport, on the other hand, requires energy usually in the form of ATP, to move substances against their concentration gradient. This is where membrane proteins like P-glycoprotein come into play.

P-glycoprotein is crucial for active transport. It pumps various substances, including drugs, out of cells, thus maintaining cellular homeostasis. This aspect of membrane transport is pivotal for removing toxic substances and, unfortunately, can contribute to drug resistance.

Drug Efflux

Drug efflux is a biological process where cells transport drugs out, effectively lowering the drug concentration inside the cell. This is achieved via specialized proteins embedded in the cell membrane, like P-glycoprotein. The dynamic process is essential for protecting cells from potentially harmful compounds.
Through active transport, P-glycoprotein uses ATP to expel drugs, including chemotherapeutics, from the intracellular to the extracellular space. This mechanism:

• Prevents accumulation of toxic substances inside the cell.
• Plays a significant role in protecting tissues that are prone to exposure to xenobiotics, which are foreign chemical substances.

Drug efflux is a double-edged sword. While it guards cells, it can also limit the effectiveness of therapeutic treatments by pumping out drugs needed to treat diseases, leading to multidrug resistance.

Chemotherapeutic Resistance

Chemotherapeutic resistance is a significant challenge in cancer treatment, where cancer cells become less responsive to chemotherapy. P-glycoprotein is a key player in this phenomenon. It reduces the intracellular concentration of drugs, thus decreasing their effectiveness.
The development of resistance can occur through:

• Increased expression of drug efflux pumps like P-glycoprotein, which actively expel chemotherapeutic agents.
• Mutation in target proteins, rendering drugs less effective.
• Enhanced DNA repair mechanisms that counteract the effects of chemotherapy.

Understanding and overcoming chemotherapeutic resistance is vital for improving cancer treatment outcomes. Research focuses on developing inhibitors of P-glycoprotein that can work alongside chemotherapy to ensure higher drug retention within cancer cells.