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Hexokinase: Inhibited by Glucose-6-phosphate.
Hexokinase converts glucose into glucose-6-phosphate by adding a phosphate group.
Glucose-6-phosphate and fructose-6-phosphate stay in equilibrium in the cell→ due to this, if phosphofructokinase is inhibited, fructose-6-phosphate will be increased, and therefore so will glucose-6-phosphate. → this inhibits hexokinase from converting glucose at all.
*Note: This inhibition has a low Km, so only a slight excess of glucose-6-phosphate will cause inhibition.
Pyruvate Kinase: This is inhibited by ATP.
Pyruvate kinase generates the final ATP from PEP. If you have enough ATP, do not need to convert it!
Feedback Loop: Fructose-1,6-biphosphate activates pyruvate kinase.
Phosphofructokinase: Inhibited by ATP; Activated by AMP; Inhibited by low pH (high H+)
Phosphofructokinase is the enzyme that catalyzes the phosphorylation of Fructose-6-phosphate to make Fructose-1,6-bisphosphate.
Additionally, it is the key step in glycolysis. Once this enzyme adds the phosphate group, it is committed to becoming pyruvate. Otherwise, it can follow another pathway and become glycogen (since glucose also works to build fatty acids).
What is AMP?
When there are low levels of ATP, there is an enzyme “adenylate kinase” which will take two ADP molecules and convert them to ATP and AMP by moving a phosphate.
ADP + ADP→ ATP + AMP
(ATP: Adenosine TRIphosphate; ADP Adenosine DIphosphate; AMP: Adenosine MONOphosphate.)
So, why would phosphofructokinase be inhibited by ATP but activated by AMP?
Each of these molecules are indicative of an energy “state” in the body.
“The Energy Charge Ratio” → ATP/AMP; this tells us how much ATP, or energy, our cells have. Conceptually, if ATP is really high, we have a lot of energy (aka, a high energy charge ratio), if AMP is really high, we have low amounts of energy (aka, a low energy charge ratio).
AMP is a low energy state as it tells us that the cell has to convert ADP to AMP and ATP to get energy, letting us know that we may be depleting our resources and need more ATP. With that in mind, we can say that when we have high ATP, we do not need more energy. This also means that we are not using much energy, so this is indicative of the resting state.
On the other hand, when we have high AMP (or low ATP), we are in need of more energy, which would tell us we are using a lot and are in the active state.
What happens?
At high levels of AMP, AMP will bind to phosphofructokinase and activate it. It binds with a HIGHER affinity than ATP! At high levels of ATP, ATP will bind to phosphofructokinase and inhibit it.
Why does H+ (low pH) inhibit phosphofructokinase?
In the absence of oxygen, cells undergo lactic acid fermentation using the products of glycolysis. It results in the build up of lactic acid, which increases acidity (Increasing H+ concentration, and lowering pH). In order to prevent tissue damage from the acidic environment, phosphofructokinase is inhibited, and does not allow the reaction to proceed.
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