Phosphofructokinase-1 (PFK-1) is one of the most important regulatory enzymes of
ID: 164795 • Letter: P
Question
Phosphofructokinase-1 (PFK-1) is one of the most important regulatory enzymes of glycolysis. Your laboratory experiments with mice model indicates that PFK1 is allosterically inhibited by high levels of ATP but AMP reverses the inhibitory action of ATP. Therefore, the activity of the enzyme increases when the cellular ATP/AMP ratio is lowered. Recently you have found that PFK1 has two sites on its structure with different affinities for ATP which is both a substrate and an inhibitor. You have also found that acidic environment increases the inhibitory efficiency of the ATP on PFK-1. our continued research efforts now indicate that PFK-1 may be responsible for early cancer growth – the cancer cells, to meet their energy requirements, survive more effectively when they have a hyperactive PFK-1 enzyme.
In addition to ATP, there are other factors that can exert allosteric control over PFK-1 activity:
Phosphoenolpyruvic acid decreases the activity
Citrate decreases the activity
PFK is inhibited by the presence of glucagon.
What set of conclusions you can draw from this new information
Explanation / Answer
Answer:
PFK is an allosteric enzyme which transits from from its T-state (Tensed, inactive) to R-state (Relaxed, active) and catalyzes the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate.
The conclusions which can be drawn from the above set of information are:
Overall conclusions: PFK-1 activity is tightly regulated such that glycolysis and gluconeogenesis doesn't occur simultaneously.
Individual conclusions:
1. When the cellular ATP/AMP is lowered, the activity of PFK-1 increases, depicting that glycolysis is stimulated when the energy level in the cell falls.
2. Low levels of pH inhibits activity of PFK-1. This is inorder to protect the cells from damage due to accumulation of acids (such as lactic acid) in the muscles.
3. Glucagon activates protein kinase-A and shuts down the activity of PFK-2. This inhibits formation of F-2,6-bisphosphate from fructose-6-phosphate, thereby inhibiting PFK-1.