Enzyme regulation by negative feedback (feedback inhibition) involves which of the following mechanisms?

• A. A downstream enzyme phosphorylates an upstream enzyme, permanently increasing its catalytic efficiency
• B. The substrate binds to the enzyme active site and irreversibly inactivates the enzyme by covalent modification
• C. A hormone increases gene transcription of all enzymes in the pathway to raise the final product concentration
• D. The end product of a metabolic pathway binds to an allosteric site on an early enzyme in the pathway and decreases its activity

Answer: (D)

Verified step by step guidance

1. Step 1: Understand the concept of feedback inhibition in enzyme regulation. Feedback inhibition occurs when the end product of a metabolic pathway binds to an enzyme that acts early in the pathway, reducing its activity to prevent overproduction.
2. Step 2: Identify the type of enzyme regulation involved. Feedback inhibition typically involves allosteric regulation, where the end product binds to an allosteric site (a site other than the active site) on the enzyme, causing a conformational change that decreases enzyme activity.
3. Step 3: Differentiate feedback inhibition from other mechanisms. For example, phosphorylation can modify enzyme activity but is not necessarily feedback inhibition; irreversible covalent modification by substrate is not typical feedback inhibition; and increasing gene transcription affects enzyme levels but is not immediate feedback inhibition.
4. Step 4: Recognize that feedback inhibition is a reversible and rapid regulatory mechanism that helps maintain homeostasis by controlling the flux through a metabolic pathway based on the concentration of the end product.
5. Step 5: Conclude that the correct mechanism is when the end product binds to an allosteric site on an early enzyme in the pathway and decreases its activity, thereby regulating the pathway through negative feedback.