Question

RECALL Discuss the role of feedback inhibition in the anabolism of purine-containing nucleotides.

Short answer

Feedback inhibition in purine synthesis involves AMP and GMP inhibiting an initial enzyme, ensuring balanced nucleotide production.

Step-by-step solution

- Understand Feedback Inhibition

Feedback inhibition is a mechanism where the end product of a metabolic pathway inhibits an enzyme involved in the pathway. This prevents the overproduction of the end product.

- Identify anabolism of Purine Nucleotides

The anabolism of purine-containing nucleotides involves several steps in which simple molecules are converted into complex molecules like AMP (adenosine monophosphate) and GMP (guanosine monophosphate).

- Role of Feedback Inhibition in Purine Synthesis

In the synthesis of purine nucleotides, feedback inhibition occurs when the end products, AMP and GMP, inhibit the activity of the first committed enzyme in the purine synthesis pathway, glutamine-PRPP amidotransferase.

- Mechanism of Feedback Inhibition

When AMP and GMP concentrations are high, they bind to the enzyme glutamine-PRPP amidotransferase, reducing its activity. This limits the ability of the pathway to continue producing additional purine nucleotides, ensuring homeostasis.

- Importance of Feedback Inhibition

This mechanism is crucial for maintaining the balance of nucleotide pools in the cell, preventing the waste of resources and potential toxicity due to an excess of purine nucleotides.

Key concepts

Anabolism of Purine Nucleotides

Anabolism is the process of building complex molecules from simpler ones.
In the case of purine nucleotides, this involves several steps where basic molecules like ribose-5-phosphate are transformed into nucleotides such as AMP (adenosine monophosphate) and GMP (guanosine monophosphate).
This process is crucial for many cellular functions.
Think of it like a factory assembly line, adding components step-by-step to create a finished product.
The process is energy-intensive and carefully regulated to meet the cell's needs without wasting resources.
One key point is that feedback inhibition helps regulate the entire pathway efficiently, ensuring balance and homeostasis.

AMP Synthesis

AMP, or adenosine monophosphate, is synthesized from a precursor called inosine monophosphate (IMP).
The transformation involves a two-step reaction which requires energy, usually obtained from GTP (guanosine triphosphate).
First, adenylosuccinate synthetase enzyme catalyzes the addition of aspartate to IMP, forming adenylosuccinate.
This is then converted into AMP by adenylosuccinate lyase, which removes a fumarate molecule.
Because these reactions are expensive in terms of energy, the process is tightly regulated by feedback inhibition.
When AMP levels are high, they inhibit adenylosuccinate synthetase, thus slowing down or halting the production of AMP.

GMP Synthesis

The synthesis of GMP (guanosine monophosphate) begins with IMP, similar to AMP synthesis.
However, the pathway diverges here.
IMP is first oxidized to xanthosine monophosphate (XMP) by the enzyme IMP dehydrogenase.
Next, XMP is converted into GMP by the enzyme GMP synthetase, which requires ATP (adenosine triphosphate) and glutamine.
Like AMP synthesis, GMP synthesis is also tightly controlled by feedback inhibition.
High levels of GMP inhibit IMP dehydrogenase, ensuring that the production of GMP is not excessive.
This regulation keeps the purine nucleotide levels balanced in the cell.

Glutamine-PRPP Amidotransferase

Glutamine-PRPP amidotransferase is the key regulatory enzyme in purine nucleotide synthesis.
It catalyzes the first committed step of the pathway, converting PRPP (phosphoribosyl pyrophosphate) and glutamine into 5-phosphoribosylamine.
This enzyme's activity is crucial because it sets the rate for purine nucleotide synthesis.
Feedback inhibition plays a vital role here.
When the end products, AMP and GMP, accumulate, they bind to glutamine-PRPP amidotransferase and inhibit its activity.
This prevents overproduction of purine nucleotides, ensuring homeostasis.
The inhibition of this enzyme demonstrates an efficient way for the cell to conserve energy and resources.