Regulation of Glycolysis

Question 1

What are the major control sites of Glycolysis?

Answer 1

1. Hexokinase
2. Phosphofructokinase (PFK)
3. Pyruvate Kinase

Question 2

What is regulated in Glycolysis?

Answer 2

The hexose transporters, which are responsible for the transport of glucose into the cell.

For most mammalian cells, intracellular glucose is less than blood glucose, so glucose moves into cells via active transport.

Once inside the cell glucose is phosphorylated and cannot cross plasma membrane.

Question 3

Regulation of Hexokinase

Answer 3

RXN 1

Glucose-6-Phosphate allosterically inhibits Hexokinase isoenzymes I, II and III.

Glucose-6-Phosphate increases when glycolysis is inhibited at sites along the pathway.

Glucokinase has a a km of 2-5mM for glucose, so it is not inhibited by G-6-P.

Liver cells can form G-6-P by action of glucokinase when glucose is abundant and other cells have efficient glucose.

Question 4

Phosphofructokinase Inhibitors

Answer 4

Inhibitors: ATP, citrate and H+

ATP lowers enzyme affinity for Fructose-6-Phosphate.

Citrate is an early intermediate in the citric acid cycle.

Inhibitory action of ATP is reversed by AMP, so that PFK activity increases when the ATP/AMP ratio decreases.

Question 5

Phosphofructokinase Activators

Answer 5

Activators: AMP, Fructose-2,6-bisphosphate

F-2,6-BP activates PFK in the liver by increasing the affinity for F-6-P and decreasing the inhibitory effect of ATP.

Question 6

Pyruvate Kinase

Answer 6

High ATP reduces affinity of PK for PEP.

Fructose-1,6-bisPhosphate activates Pyruvate kinase.

Pyruvate Kinase is inhibited by Acetyl-CoA, which is a product of FA oxidation

Question 7

Regulation Summary

Answer 7

Phosphofructokinase is allosterically inhibited by ATP, this inhibition is relieved by AMP.

Citrate inhibits phosphofructokinase.

The build up of fructose-6-phosphate, stimulates the formation of fructose-2,6-bisphosphate, which in turn stimulates phosphofructokinase.

The enzyme which synthesises fructose-2,6-bisphosphate (PFK2) and the enzyme which hydrolyses it back to fructose-6-phosphate (FBPase2) regulated by glucagon, causes glycolysis to slow down when blood glucose falls.

Phosphofructokinase is inhibited by H+ ions, which prevents the excessive for,still of lactate u dear anaerobic conditions.

Hexokinase is inhibited by glucose-6-phosphate, which builds up after phosphofructokinase is inhibited.

Pyruvate Kinase is activated by fructose-1,6-bisphosphate but is allosterically inhibited by ATP.