Glycolysis – A Key Metabolic Pathway

A man exercising. The biochemical reactions are driven in part by glycolysis.
Image by StockSnap, c/o Pixabay.

Glycolysis is one of the cells main ways of generating energy as well as producing intermediates for other reactions. In the old days, the pathways was called the Embden-Meyerhof pathways.

The word comes from the combination of two ancient greek words, glykys meaning sweet and lysis which means splitting.

In the process, one molecule of glucose which is a 6-carbon molecule is broken down into two molecules of pyruvate (a 3-carbon molecule).

Free energy is released in the process is stored as 2 molecules of ATP and 2 molecules of NADH. 

There are ten steps involved in glycolysis.

Step 1: Conversion of glucose to glucose 6-phosphate

A glucose molecule is has a phospahte group added to it using the enzyme hexokinase. A molecule of ATP is used up and generates ADP. It is interesting to note that using an ATP molecule so early on means the whole process is in an energy ‘debt’ because the pathway needs to get started.

Step 2: The conversion of glucose 6-phosphate to its isomer fructose 6-phosphate

The enzyme phosphoglucoisomerase catalyses this reaction.

This is a classic example of conversion of an aldose to a ketose.

Step 3: The substrate, fructose-6-phosphate is phosphorylated by phosphofructokinase to fructose-1,6-bisphosphate.

A second phosphate group is added from ATP.

Step 4 : The product of step 3, fructose-1,6-bisphosphate is split into two 3-carbon intermediates by the enzyme aldolase.

It forms glyceraldehyde-3-phosphate which becomes the substrate of the next reaction – Dihydroxyacetone phosphate.

Step 5:  Dihydroxyacetone phosphate (DHAP) is rearranged into a second glyceraldehyde-3-phosphate by the enzyme triose phosphate isomerase (TPI).

Glyceraldehyde-3-phosphate is then the only substrate for the next reaction.

Step 6: The substrate, glyceraldehyde-3-phosphate is oxidized to a carboxylic acid by glyceraldehyde- 3-phosphate dehydrogenase.

The reaction reduces NAD+ to NADH. The  product is 1,3-bisphosphoglycerate. Here, a  new phosphate group is attached with a “high-energy” bond.

Step 7: This step critically harvests energy in the form of ATP.

The molecule, 1,3-bisphosphoglycerate has a high energy phosphate group which is transferred to ADP by phosphoglycerate kinase. In the reaction, 3-phosphoglycerate and ATP are created. It is also worth noting that this is the first reaction involving substrate level phosphorylation in glycolysis.

Step 8: The molecule,  3-phosphoglycerate is isomerized into 2-phosphoglycerate by the enzyme phosphoglycerate mutase.

This reaction involves moving the phosphate group from carbon-3 of 3-phosphoglycerate to carbon-2.

Step 9:  The enzyme enolase catalyzes the dehydration of 2-phospholgycerate to phosphoenolpyruvate (PEP).

The creation of phosphoenolpyruvate makes this one of the highest energy phosphorylated compounds in metabolism. It’s an important reaction and critical in the way metabolism is driven.

Step 10: The final substrate-level dehydration in the pathway.

Phosphoenolpyruvate (PEP) serves as a donor of the phosphoryl group which is transferred to ADP by pyruvate kinase making ATP and releasing a water molecule.

Pyruvate is the final product of glycolysis and usually enters the TCA cycle.

What happens to pyruvate?

Pyruvate is converted to acetyl CoA. It is formed under aerobic conditions.

When the cell is under anaerobic conditions, then lactate is produced.

In fermentation, ethanol is produced.

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