Glycolysis and the Acetyl CoA step

Hey all, this post will be part of our AP Bio/ General Bio series! Keep up with the blog for more content like this!

Cellular Respiration is the process of converting glucose molecules to molecules of ATP, used in various cell processes. There are three main stages of respiration: Glycolysis, the Krebs cycle, and the Electron Transport Chain/ Chemiosmosis. In this post we will focus on Glycolysis and the subsequent Acetyl CoA step.


All cells undergo Glycolysis  in the cytosol of their cytoplasm where for each Glucose molecule(6 carbon), 2 pyruvate molecules (3 carbon each) are produced. Glycolysis occurs due to the hydrolysis of the third high energy bond in ATP which is coupled to endergonic reactions of breaking the glucose down. This occurs because there is a lot of energy in glucose that can be used for ATP production.

Glycolysis has 10 main steps and each step has an associated enzyme that catalyzes the breakdown of glucose as otherwise, it would take far too long for this process to occur in a manner that can support life.

For Glycolysis to occur, oxygen isn’t needed but for the pyruvate molecules produced to go into the Krebs cycle and ETC, oxygen is needed. If there is no oxygen available, the pyruvate undergoes reduction in Fermentation (Alcoholic or Lactic Acid) to produce Ethanol or Lactic Acid waste respectively.

Before we dive into the steps of Glycolysis some things may need to made clear. In the ETC section of cell respiration, redox (reduction – oxidation) reactions are essential (for reasons we will see in a later post). Thus in Glycolysis and Krebs cycle, many coenzymes (electron carriers) are produced to help out later in the ETC process to increase ATP yield. One of these enzymes ins NAD+ (Nicotinamide Adenine Dinucleotide) which when reduced (electron added) becomes NADH +  H+. Another important coenzyme is FAD.

Steps of Glycolysis:

There are two main stages of Glycolysis: Energy Investment and Energy Payoff. In the Investment phase, two ATP are used to change glucose into a higher energy state so that it is easier to break it up. Once broken up, there are two intermediate molecules produced that create 2 ATP each (4 ATP) for a 2 ATP net gain for Glycolysis in the Energy Payoff phase.


Step 1: Glucose is phosphorylated with the phosphate group attaching to the 6 Carbon. This creates the molecule Glucose-6-Phosphate. This occurs with the help of the enzyme Hexokinase.

Step 2: Glucose 6 Phosphate is converted to its isomer Fructose-6- Phosphate by the Isomerase enzyme. The reason this occurs is to make the molecule even more energized so as to maximize yield later.

Step 3: The Fructose-6-Phosphate from Step 2 is phosphorylated again to form Fructose-1,6-Bisphosphate. This step makes the molecule extremely energized and unstable – it wants to be broken down. This step occurs with help from Phosphofructokinase.

Step 4: This is where the split happens. Fructose-1,6-Bisphosphate splits into two molecules: Glyceraldehyde-3-Phosphate (G3P) and Dihydroxyacetone Phosphate. Each of these molecule will have 3 carbons.

Step 5: G3P and its isomer are in equilibrium with each other. As G3P is used up more of the isomer will be converted to G3P and will continue to be used.

Review: 2 ATP used, 2 3 carbon molecules produced

Next onto the Energy Payoff Phase:


Step 6: G3P is oxidized and phosphorylated (with a free phosphate) as NAD is reduced to produce 1 NADH +H and a 1,3 Bisphosphoglycerate. Remember, this is for each G3P. This is a coupled reaction.

Step 7: A phosphate group is removed from each 1,3 Bisphosphoglycerate to make 2 ATP (per G3P so 4 per glucose). This an example of substrate level phosphorylation as ADP becomes ATP through phosphorylation with energy input from another molecule. This step occurs with the help of phospho-glucokinase.

Step 8: Molecule from step 7 energized further by rearranging the placement of the phosphate group.

Step 9: A water molecule is removed and Phosphoenolpyruvate (PEP) is produced.

Step 10: The  PEP molecule from step 9 have their phosphate groups taken away to yield a pyruvate (2 per glucose)

NET: 2 ATP, 2 H2O, 2 NADH + H

Now, if oxygen is present pyruvate will be converted to Acetyl CoA, used in the Krebs cycle. First, decarboxylation will occur where are CO2 is removed from pyruvate. Next, another NAD will be reduced. Finally coenzyme A will attach. This molecule is also now in the Mitochondrion.


If oxygen is not present (anaerobic) then there are two potential processes that can occur: Alcoholic Fermentation and Lactic Acid Fermentation. In the former, Pyruvate will be converted to Ethanal and decarboxylated (releases CO2). The Ethanal will then be reduced to Ethanol. This occurs mainly in bacteria. In the latter process, Pyruvate will be reduced to Lactic Acid. Both Ethanol and Lactic Acid are waste products.


Article by Sai Rachakonda

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