Allosteric Regulation in The Liver

Phosphofructokinase 

1. 1. Inhibited by: citrate

• Citrate now inhibits PFK (I am starting to get tired of writing it out so much…) . This is because citrate is the first product of the TCA cycle in the mitochondria, so if it is in excess, the liver knows that it does not need to produce any more as there will be enough ATP made, and it can store glucose as glycogen. 

• What citrate does is increase the ability of ATP to bind to and inhibit PFK. 

1. 2. Inhibited by: ATP

• The same thing happens with ATP

Pyruvate Kinase

2. 1. ATP inhibition

   2. Alanine inhibition

Again, ATP works the same. 

• Another pathway that pyruvate can follow is to eventually form alanine. When there is an increase of alanine in the cell, pyruvate kinase knows that it does not need to keep producing pyruvate since it is not needed, and will be inhibited. 

While we are on the topic of pyruvate kinase, there is something strange it does in liver cells. 

→ It has an extra layer of inhibition built in that is not present in muscle cells...

Phosphorylation! When it is phosphorylated, it is less active. When it is unphosphorylated, it is more active. 

• At HIGH blood glucose levels, it is dephosphorylated 

• At LOW blood glucose levels, it is phosphorylated. 

Why? 

Our liver is meant to regulate the amount of glucose in the blood. It does not want there to be too much or too little. Therefore, when we are in a fasted state, we need to figure out a way to keep glucose levels relatively constant. To do this, a kinase comes along and phosphorylates pyruvate kinase to lower its activation. This allows for the accumulation of PEP, which allows for the process of glucogenesis to reestablish the levels of glucose in the blood!