Regulation of glycolysis
In glycolysis glucose is partially oxidized to provide energy for the cell. Therefore, when the cell has plenty of energy available to meet its metabolic needs, the activity of critical enzymes will be reduced in order to suppress glycolysis. Alternatively, when the cell is in need of energy, it will turn glycolysis on by increasing the activity of these enzymes.
The regulation of this pathway occurs at three key points where the enzyme reactions involved are irreversible. These three enzymes are hexokinase, phosphofructokinase and pyruvate kinase. Inhibition of glycolysis is a mechanism to conserve energy by preventing the breakdown of adenosine triphosphate.
Methods of Regulation
Glycolysis is regulated by: The concentration of glucose in the blood, the relative concentration of critical enzymes, the competition for the intermediate products of glycolysis and the levels of certain hormones in the bloodstream.
Uptake of glucose from blood
- The level of glucose present in a cell determines the availability of sugar for oxidation via glycolysis. Glucose transport in cell is regulated by several cell surface receptors which are under the control of insulin.
- Insulin upregulates the level of glucose transporters Glut-3 or Glut-4 and increase the uptake of glucose from blood stream.
- In addition, insulin also regulates breakdown of glycogen to increase the amount of available glucose.
Covalent Modification of Enzyme
- Most of the typical protein kinases are regulated by a reversible phosphorylation and dephosphorylation.
- In the presence of low glucose in blood, pyruvate kinase is getting phosphorylated by cytosolic enzymes and phosphorylated pyruvate kinase is less active. Similarly in the presence of high blood glucose level, it remains as unphosphorylated and that relive the inhibition caused by phosphorylation.
- All the three crucial enzymes Hexokinase, phosphofructokinase and pyruvate kinase of glycolysis are regulated allosterically.
- In an allosteric regulation, an enzyme binds the allosteric molecules and this modulates the activity of the enzyme either in positive or negative manner.
Levels of hormone in blood stream
- Humans and other mammals produce the hormone insulin in response to the ingestion of carbohydrates. High sugar levels stimulate the pancreas to produce insulin, which enhances the entry of glucose into the cell and increases the production of the critical glycolysis enzymes. These actions stimulate glycolysis and lower blood glucose levels.
- Alternatively, low blood sugar levels depress insulin production and stimulate the pancreas to release the hormone glucagon, which inhibits glycolysis.
Regulation of Glycolysis takes place at three irreversible reactions:
1) Conversion of D-glucose into glucose-6-phosphate by Hexokinase
2) Conversion of fructose-6-phosphate to fructose- 1, 6-bisphosphate (FBP) by PFK 1
3) Conversion of phosphoenolpyruvate into pyruvate by pyruvate kinase
Table: Summary of regulation of glycolysis