Thursday, May 26, 2011

Understanding Glycolysis: Steps 1 & 2

Glycolysis is the first metabolic pathway of cellular respiration.  Cellular respiration is a metabolic process that cells use to make energy.  It is a catabolic process which means that complex organic molecules are broken down/degraded/catabolized to produce simple cellular metabolites (simple molecules that the cell uses for anabolic/synthesis pathways. 

During glycolysis, glucose is oxidized to form two molecules of pyruvate.  Glucose is a six carbon molecule and pyruvate is a three carbon molecule.  Glycolysis involves 10 steps.

Step 1:  Glucose is phosphorylated to form glucose-6-phosphate (G-6-P) by the enzyme hexokinase.  In liver cells, glucose is phosphorylated by a hexokinase commonly referred to as glucokinase and not hexokinase.

Why is glucose phosphorylated? 
It is phosphorylated to keep glucose sequestered/trapped inside the cell.  Glucose can enter or exit the cell via glucose transport proteins located in the plasma membrane.  However, there are no transport proteins for G-6-P.

What is the difference between hexokinase and glucokinase (liver enzyme)?
The hexokinase that is found in skeletal muscle and other cells (except liver cells) has a very small KM value.  KM is the Michaelis-Menten kinetic constant that is used to approximate the affinity of the enzyme for the substrate.  A small KM value indicates that the enzyme has a very high affinity for the substrate whereas a large KM value indicates a low affinity for the substrate.  Hexokinases have a very high affinity for glucose and therefore these enzymes reach a Vmax (maximum velocity) much faster than the liver glucokinase. The active sites of hexokinases quickly become saturated by the substrate glucose.

Liver glucokinases do not reach Vmax as quickly or become saturated as quickly.  What is the significance of this kinetic difference?  One of the functions of the liver is to regulate blood glucose levels.  When blood glucose levels exceed 5mM the liver is able to take up a higher concentration of glucose due to the glucokinase (aka hexokinase D).

Step 2:  Glucose 6-Phosphate is converted to fructose-6-phosphate by the enzyme phosphoglucose isomerase (PGI). 

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