Question

Training Question 3. Shown below is the activity profile for the enzyme phosphofructokinase-1 (PFK-1) which catalyzes the reaction: Fructose 6-phosphate + ATP → fructose 1,6-biphosphate + ADP. Low (ATPI PFK-1 activity High (ATP) [Fructose 6-phosphatel Describe the different patterns of regulation for different ATP levels. Explain the why such regulation is appropriate for this enzyme, given its role in metabolism.

Answer 1

Describe the different patterns of regulation-

Answer- Phosphofructokinase-1 enzyme is a critical enzyme in the glycolysis process, which catalyzes one of the major irreversible steps of glycolysis. ATP, AMP, and citrate are significant regulators of this enzyme. ATP is mainly an inhibitor of the process catalyzed by the PFK-1. This enzyme is also a checkpoint for the regulation of the glycolysis process. The enzyme structure, as reported in biochemistry texts, suggests that it is a tetramer that exists in two conformational states, R and T state. PFK-1 has two binding sites for ATP- substrate site and inhibitory site. ATP is a substrate and inhibitor of this enzyme, while it can bind to both states; ATP preferentially binds to the T state. This binding causes an R-T switch while the F 6 P binds to the R state. An increase in ATP leads to increased inhibition of the PFK enzyme since the inhibitory site binds ATP in the T state. This enzymatic inhibition is called allosteric inhibition and is a crucial step in glycolysis. In simple terms, it means that when ATP is less, the F6P to F1,6P reaction is promoted and inhibited when ATP is high, which means ATP acts a negative response to enzyme activity.

Explain why such regulation is appropriate-

Answer- ATP is the energy currency of the cell, therefore in simple terms, the energy need of the cell drives the glycolysis reaction to occur. If the cell has sufficient ATP, the PFK-1 catalyzed step is inhibited; if the energy is low, then the step takes place based on energy requirements. Thus this regulation is a critical regulatory step of glycolysis and cellular respiration.