Glycolysis

Glycolysis is a biochemical process that cells perform to metabolize glucose and generate

energy. This energy is contained in a molecule called ATP (adenosine triphosphate) and is

the main source of fuel in many cellular processes. Glucose is a 6-carbon sugar that the

body gets from eating carbohydrates like bread, pasta, rice, vegetables, etc.

(Lumen Learning, 2021)

The Importance of Pyruvate

In glycolysis, glucose is converted to a molecule called pyruvate, a 3-carbon sugar. Pyruvate

is a crucial molecule in metabolism. It is the starting component to many different

biochemical pathways. Below lists several paths it may take:

- Krebs cycle (also referred to as citric acid cycle or TCA cycle): this process occurs in

the mitochondria of the cell, where more ATP can be generated along with

coenzymes such as NADH and FADH2. These are molecules that are known to

facilitate chemical reactions.

- Gluconeogenesis: used to generate more glucose in times when glucose levels are

low.
 - Fatty Acid and Protein Synthesis: required for energy storage, structural components

of cells, etc.

- Fermentation: in areas of the body where oxygen is low, anaerobic fermentation

occurs to generate lactate and ethanol. This is important for when the body needs a

quick source of energy.

The Steps to Making Pyruvate

(Bruggeman, 2002)

Glycolysis begins when glucose enters the cell’s cytoplasm. 1 The overall process can be

split into two portions: investment phase and payoff phase. 2

Investment Phase:

Step 1: Phosphorylation
Glucose becomes activated by the enzyme hexokinase. Kinase is a type of enzyme, which

its function is to phosphorylate (add a phosphate group) a molecule. It takes a phosphate

group from ATP. This activates the molecule, giving it energy. Once Glucose is

phosphorylated, it becomes G6P (Glucose 6-phosphate). This is called an investment

because an ATP had to be used.

Step 2: Isomerization

Isomerization is the process of rearranging the G6P molecule into F6P (Fructose 6-

phosphate). This increases the overall energy of the molecule. Increasing the energy of the

molecule will help drive the reaction forward.

Step 3: Phosphorylation

In this step, another investment is made. Another kinase enzyme, phosphofructokinase

(PFK) takes phosphate from a second ATP molecule to phosphorylate F6P.

Step 4: Lysis

F6P is then split into two 3-carbon molecules: dihydroxyacetone (DHAP) and glyceraldehyde

3 -phosphate (G3P). This is facilitated by the enzyme aldolase.

Step 5: Isomerization

DHAP could not proceed onto glycolysis in this form. Therefore, it must be isomerized

(rearranged) to G3P, which was the other molecule made in the previous step.

Payoff Phase

Step 6: Oxidation
This step includes two different reactions, both facilitated by the enzyme, glyceraldehyde 3-

phosphate dehydrogenase (GAPDH). A coenzyme NAD+ is also used in this step. NAD+ is

reduced (electron is added) into NADH and a phosphate group gets added, creating 1,3-

biphosphoglycerate (1,3 BPG).

Step 7: Substrate Level Phosphorylation

1,3 BPG will then have its phosphate group removed by phosphoglycerate kinase (PGK) so

that it can phosphorylate an ADP molecule, thereby generating an ATP molecule. When 1,3

BPG lost a phosphate group, it has now become 3-phosphoglycerate (3PG)

After this step, the 2 ATP that was invested has now been made up.

Step 8: Isomerization

3PG is rearranged into 2-phosphoglycerate (2PG) by the enzyme phosphoglycerate mutase.

Step 9: Dehydration

2 PG then has a water molecule removed from it by the enzyme enolase, becoming

phosphoenolpyruvate (PEP)

Step 10: Substrate Level Phosphorylation

PEP then has its phosphate group stripped away by the enzyme pyruvate kinase. This

phosphate is then used to phosphorylate an ADP molecule to make ATP.

Now there has been a total of 4 ATP generated, making a net gain of 2 ATP.

How is it Controlled?

It is essential that the steps of a biochemical pathway are under control so that there is no

excess of a particular product. In this case, these steps are controlled by concentration of
glucose or the intermediate molecules. This is done by competitive inhibition which is

where a molecule will compete for the enzyme used. When the concentration of the product

is high, it can bind to the enzyme, where the initial substrate would usually bind to stop the

process from continuing, thereby regulating the production of more products.

Glycolysis and Disease

The process of glycolysis is particularly important in helping find treatments for diabetes

especially since it is the main pathway in trying to break down glucose. 3

There have also been many studies that focus on the process of glycolysis when treating

cancer. Tumor cells rely a lot on glycolysis for continual growth. 4 Studies show that altering

some of the enzymes used in glycolysis can contribute to treating cancer.

References

1. Bailey, R. (2020). Glycolysis: The First Stage in Cellular Respiration.

https://www.thoughtco.com/steps-of-glycolysis-373394
2. Chaudhry, R., Varacallo, M. (2020). Biochemistry, Glycolysis.
https://www.ncbi.nlm.nih.gov/books/NBK482303/
3. Stienstra, R. Netea, M. G. (2018). Firing Up Glycolysis: BCG Vaccination Effects on
Type 1 Diabetes Mellitus. Trends in Endocrinology & Metabolism. 29(12), 1043-2760.
https://doi.org/10.1016/j.tem.2018.10.001
4. Enzo, E., Santinon, G., Pocaterra, A., Aragona, M., Bresolin, S., Forcato, M., . . .
Dupont, S. (2015). Aerobic glycolysis tunes yap / taz transcriptional activity. The EMBO
Journal, 34(10), 1349-1370. doi:10.15252/embj.201490379

5. Learning, L. (n.d.). Glycolysis. Lumen. https://courses.lumenlearning.com/wm-

biology1/chapter/reading-glycolysis-2/.