Sunday, June 12, 2011

Second Half of Glycolysis

The last five reactions of glycolysis leads to production of two pyruvate molecules.  The last five reactions are called the energy harvesting or energy payoff phase.

Reaction 6:  Glyceraldehyde-P  Dehydrogenase Reaction
G3P is converted to 1, 3 bisphosphoglycerate

This is the first reaction in glycolysis to generate a NADH molecule.  NADH is an electron carrier that is used in the mitochondrion by the ETC to generate ATP.

Reaction 7:  Phosphoglycerate kinase converts 1,3 BPG to 3-phosphoglycerate.  It is the first step of glycolysis to generate ATP via substrate level phosphorylation.  A phosphate group is removed from 1,3 BPG and transferred to ADP to form ATP (substrate-level phosphorylation).

Reaction 8:  Phosphoglycerate mutase converts 3-phosphoglycerate to 2-phosphoglycerate. 

What is the purpose of this reaction?
This rearrangement of the phosphate from the C-3 to C-2 position allows productio of phosphoenolpyruvate in the next reaction.

Reaction 9:  Enolase converts 2-PG to PEP

Reaction 10:  Pyruvate kinase converts PEP to pyruvate and also generates ATP via substrate level phosphorylation.

Summary of the First Five Reactions in Glycolysis

The first five reactions of glycolysis are referred to as the energy investment phase or energy input phase.  These reactions initially use ATP.  Reaction 1 uses an ATP molecule to convert glucose to glucose 6-phosphate.  This input of energy is similar to priming a pump.  Some energy must be used to initiate or start the reactions of the glycolytic pathway.Reaction 3 uses a second ATP molecule to convert F6P to F 1,6-BP. 

The first phase converts glucose (a 6 carbon molecule) to two glyceralde 3-phosphate molecules (3 carbon molecules).

Steps 4 & 5 of Glycolysis

In step 4 fructose 1,6-bisphosphate is cleaved by fructose bisphosphate aldolase to form dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (G3P).  This reaction is unfavorable written at standard state.  Cellularly, the change in free energy is close to zero. 

In step 5 DHAP is converted to G3P by triose phosphate isomerase.

Why is DHAP converted to G3P?
The purpose of this reaction is to allow both products of the aldolase reaction to continue in glycolysis.

Friday, May 27, 2011

Step 3: The Committed Step in Glycolysis

In step 3 fructose-6-phosphate is converted to fructose 1,6 bisphosphate by the enzyme phosphofructokinase (PFK-1).  Phosphofructokinase is highly regulated inside the cell. 

Why is step 3 the committed step in glycolysis?

Step 3 is an irreversible reaction whereas steps 1 & 2 are reversible, however, equilibrium of these first two reactions lie to the right in favor of the reaction going forward.  The conversion of fructose-6-phosphate to fructose 1,6, bisphosphate commits the cell to carrying out glycolysis.

Overview of Reactions of Steps 1 & 2 of Glycolysis

                                       Hexokinase
Step 1:  Glucose + ATP  ------------>  Glucose-6-Phosphate   +  ADP  +  H+
                                            <--

                                               Phosphoglucose
Step 2:  Glucose-6-Phosphate  ----------------> Fructose-6-Phosphate
                                                   isomerase

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). 

Welcome

Welcome to my blog.  If you have questions about chemistry, biochemistry, genetics, or biology, then feel free to post your questions here. 

Welcome to The Science Tutorial.