The key difference between PFK-1 and PFK-2 is that PFK-1 catalyzes the conversion of fructose 6-phosphate and ATP to fructose 1,6-bisphosphate and ADP while PFK-2 catalyzes the synthesis of fructose 2,6-bisphosphate from fructose 6-phosphate.
Phosphofructokinase-1 (PFK-1) and phosphofructokinase-2 (PFK-2) are two enzymes. PFK-1 is a glycolytic enzyme that catalyzes the reaction of fructose 6-phosphate, converting it into fructose 1,6-bishosphate. It is the rate-limiting step of glycolysis. When the glucose level is high, and it is necessary to regulate glycolysis, PFK-2 catalyzes the synthesis of fructose 2,6-bisphosphate from fructose 6-phosphate. Fructose 2,6-bisphosphate is a powerful allosteric activator of PFK-1 in order to enhance the breakdown of glucose. PFK-2 is not a glycolytic enzyme. But, both PFK-1 and PFK-2 act on the same substrate.
CONTENTS
1. Overview and Key Difference
2. What is PFK-1
3. What is PFK-2
4. Similarities – PFK-1 and PFK-2
5. PFK-1 vs PFK-2 in Tabular Form
6. Summary – PFK-1 vs PFK-2
What is PFK-1?
PFK-1 is the first committed enzyme in glycolysis. In fact, it is the rate-limiting enzyme of glycolysis. It catalyzes the conversion of fructose 6-phosphate into fructose 1,6-bisphoshate. PFK-1 uses ATP for this reaction. Hence, PFK-1 is affected by the ATP concentration. The inhibition of PFK-1 by ATP is a part of the negative feedback loop that regulates glycolysis flux under an aerobic state. Other than by ATP, PFK-1 activity is regulated by several other molecules, including fructose 2,6-bisphosphate, AMP and citrate.
Figure 01: PFK-1
Fructose 2,6-bisphosphate is a powerful allosteric activator of PFK-1. At physiological conditions, PFK-1 remains inactive. When it interacts with fructose 2,6-bisphoshate, it becomes active and stimulates the glycolytic pathway to increase glucose breakdown. Flux in the direction of glycolysis is greatly increased by the fructose 2,6-bisphosphate due to its ability of allosteric activation of PFK-1. In a similar way, AMP also acts as an allosteric effector to activate PFK-1. In contrast, citrate acts as an allosteric inhibitor of PFK1. Magnesium acts as the co-factor for PFK-1.
What is PFK-2?
Fructose 2,6-bisphosphate is a metabolite that regulates glycolysis and gluconeogenesis. PFK-2 or phosphofructokinase-2 is the enzyme that catalyzes the synthesis of fructose 2,6-bisphosphate from fructose 6-phosphate. Similar to PFK-1, PFK-2 acts on the same substrate. However, unlike PFK-1, PFK-2 activity is not affected by ATP concentration. Phosphoenolpyruvate and citrate can inhibit this enzyme, while inorganic orthophosphate can stimulate the action of PFK-2.
Figure 02: PFK-2
Structurally, PFK-2 exists with fructose-2,6-bisphosphatase as a bifunctional enzyme abbreviated as PFK-2/FBPase-2. PFK-2 phosphorylates fructose 6-phosphate using ATP. On the other hand, FBPase-2 dephosphorylates fructose 2,6-bisphosphate to produce fructose 6-phosphate and Pi. Hence, PFK-2 has both kinase and phosphatase activities. When glucose level is high, insulin increases the kinase activity of PFK-2 enzyme to drive the increased synthesis of fructose 2,6-bisphosphate. It stimulates glycolysis due to the activation of PFK-1 by fructose 2,6-bisphosphate. In contrast, when phosphatase activity of PFK-2 is expressed, it breaks fructose 2,6-bisphosphate back into fructose 6-phosphate, stimulating gluconeogenesis and inhibiting glycolysis.
What are the Similarities Between PFK1 and PFK-2?
- PFK-1 and PFK-2 are two enzymes.
- The substrate of PFK-1 and PFK-2 enzymes is the same: fructose 6-phosphate.
- Both enzymes are important in the regulation of glycolysis.
- The reactions catalyzed by both enzymes yield ADP from ATP.
- Citrate can inhibit both these enzymes.
What is the Difference Between PFK-1 and PFK-2?
PFK-1 catalyzes the conversion of fructose 6-phosphate into fructose 1,6-bisphosphate. In contrast, PFK-2 catalyzes the conversion of fructose 6-phosphate into fructose 2,6-bisphosphate. So, this is the key difference between PFK1 and PFK-2. Unlike PFK-1, PFK-2 has both kinase and phosphatase activity; hence it is a bi-functional enzyme. Moreover, fructose 2,6-bisphosphate is a powerful allosteric activator of PFK-1, while PFK-2 catalyzes the synthesis of fructose 2,6-bisphosphate. Thus, this is another difference between PFK-1 and PFK-2. Most importantly, PFK-1 activity is affected by ATP, while PFK-2 activity is not affected by ATP concentration.
The following infographic lists the differences between PFK-1 and PFK-2 in tabular form for side by side comparison.
Summary – PFK-1 vs PFK-2
PFK-1 catalyzes the conversion of fructose 6-phosphate and ATP to fructose 1,6-bisphosphate and ADP. PFK-2 catalyzes the synthesis of fructose 2,6-phosphate from fructose 6-phosphate. PFK-1 activity is affected by the ATP concentration. In contrast, PFK-2 is not affected by ATP concentration. Most importantly, PFK-2 has both kinase and phosphatase activities; hence it is a bi-functional enzyme. PFK-1 is not a bi-functional enzyme. Furthermore, PFK-1 is a rate-limiting enzyme of glycolysis, while PFK-2 is not considered a glycolytic enzyme. Thus, this is the summary of the difference between PFK-1 and PFK-2.
Reference:
1. Ros, Susana, and Almut Schulze. “Balancing Glycolytic Flux: The Role OF 6-PHOSPHOFRUCTO-2-KINASE/FRUCTOSE 2,6-Bisphosphatases in Cancer Metabolism.” Cancer & Metabolism, BioMed Central, 4 Feb. 2013.
2. “Phosphofructokinase 2.” Wikipedia, Wikimedia Foundation, 5 July 2021.
Image Courtesy:
1. “Phosphofructokinase 6PFK wpmp” By Zephyris at English Wikipedia – Transferred from en.wikipedia to Commons by PatríciaR. (CC BY-SA 3.0) via Commons Wikimedia
2. “5htk” By Deposition authors: Crochet, R.B.;visualization author: User:Astrojan – (CC BY-SA 4.0) via Commons Wikimedia
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