About the Author: Raleigh is a medical student who scored in the 99th percentile on the MCAT, and used Traverse to learn and memorize pathways like Glycolysis and the Krebs Cycle
There’s a joke in medical school that you always have to relearn common pathways like the Kreb’s Cycle and Glycolysis multiple times. This is the diagram I used to learn Glycolysis once and for all (read below how).
You can create your own copy of the Glycolysis diagram here (this will allow you to re-arrange, add notes and even create flashcards)
Here’s a video of me going through the Glycolysis pathway.
The Glycolysis pathway explained
Glycolysis is a vital process in cell metabolism that forms the basis for both oxygen-dependent and oxygen-independent cellular respiration. During glycolysis, glucose is transformed into pyruvate. Glucose is a six-carbon ring molecule found in blood, typically produced by breaking down carbohydrates into sugars. It enters cells through specific transport proteins that carry it from outside the cell into the cell's liquid interior, called the cytosol, where all glycolytic enzymes are located.
The overall glycolysis reaction in the cytoplasm can be simplified as:
C6H12O6 + 2 NAD+ + 2 ADP + 2 P —> 2 pyruvic acid (CH3(C=O)COOH) + 2 ATP + 2 NADH + 2 H+
Step 1: Hexokinase
In the first step, D-glucose is converted into glucose-6-phosphate by the enzyme hexokinase.
The glucose ring is phosphorylated, meaning a phosphate group from ATP is added. This step uses one ATP molecule. Hexokinase catalyzes the phosphorylation of many six-carbon glucose-like structures. Magnesium (Mg) helps shield negative charges from phosphate groups on ATP. The product is glucose-6-phosphate (G6P), named after the phosphate group on the 6' carbon of glucose.
Step 2: Phosphoglucose Isomerase
The enzyme phosphoglucose isomerase rearranges glucose-6-phosphate (G6P) into fructose-6-phosphate (F6P).
This step involves converting G6P to F6P with the help of phosphoglucose isomerase (PI). This reaction is an isomerization, where the carbon-oxygen bond is rearranged, transforming the six-carbon ring into a five-carbon ring. The rearrangement occurs when the ring opens and then closes, with the first carbon now external to the ring.
Step 3: Phosphofructokinase
The enzyme phosphofructokinase changes fructose-6-phosphate into fructose-1,6-bisphosphate, using magnesium as a cofactor.
Fructose-6-phosphate is converted to fructose-1,6-bisphosphate (FBP). Like in step 1, another ATP molecule provides the phosphate group added to F6P. Phosphofructokinase (PFK) catalyzes this reaction, and magnesium is again involved to shield negative charges.
Step 4: Aldolase
Aldolase splits fructose-1,6-bisphosphate into two sugar isomers: dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GAP).
The enzyme aldolase cleaves FBP into two 3-carbon molecules: GAP and DHAP.
Step 5: Triosephosphate Isomerase
Triosephosphate isomerase quickly interconverts DHAP and GAP, with GAP used in the next glycolysis step.
GAP is the only molecule continuing in glycolysis. Thus, all DHAP molecules are converted to GAP by triosephosphate isomerase (TIM). At this point, there are two 3-carbon molecules, but glucose has not been fully converted to pyruvate.
Step 6: Glyceraldehyde-3-phosphate Dehydrogenase
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an enzyme that takes away hydrogen and adds an inorganic phosphate to glyceraldehyde 3-phosphate, creating 1,3-bisphosphoglycerate.
In this step, two key events happen:
- glyceraldehyde-3-phosphate is changed by the helper molecule nicotinamide adenine dinucleotide (NAD);
- a free phosphate group is added to the molecule. The enzyme responsible for this reaction is GAPDH.
GAPDH has the right structures to hold the molecule in a way that allows the NAD molecule to remove a hydrogen from the GAP, changing the NAD to NADH. The phosphate group then joins with the GAP molecule and sets it free from the enzyme, resulting in 1,3 bisphoglycerate, NADH, and a hydrogen atom.
Step 7: Phosphoglycerate Kinase
Phosphoglycerate kinase moves a phosphate group from 1,3-bisphosphoglycerate to ADP, creating ATP and 3-phosphoglycerate.
In this step, the enzyme phosphoglycerate kinase (PGK) changes 1,3 bisphoglycerate into 3-phosphoglycerate. This reaction involves the removal of a phosphate group from the starting material. The phosphate is transferred to a molecule of ADP, creating our first molecule of ATP. Since we have two molecules of 1,3 bisphoglycerate (because there were two 3-carbon products from stage 1 of glycolysis), we make two molecules of ATP at this step. This ATP production balances the first two ATP molecules we used, giving us a net of 0 ATP molecules so far in glycolysis.
Once again, a magnesium atom is involved in shielding the negative charges on the ATP molecule's phosphate groups.
Step 8: Phosphoglycerate Mutase
Phosphoglycero mutase, an enzyme, moves the phosphate from 3-phosphoglycerate's 3rd carbon to the 2nd carbon, forming 2-phosphoglycerate.
This step involves a simple rearrangement of the phosphate group on the 3 phosphoglycerate molecule, making it 2 phosphoglycerate. The enzyme responsible for this reaction is called phosphoglycerate mutase (PGM). A mutase is an enzyme that helps move a functional group from one position on a molecule to another.
The reaction happens by first adding an extra phosphate group to the 2′ position of the 3 phosphoglycerate. The enzyme then removes the phosphate from the 3′ position, leaving only the 2′ phosphate, and creating 2 phosphoglycerate. This process also restores the enzyme to its original, phosphorylated state.
Step 9: Enolase
Enolase, an enzyme, removes a water molecule from 2-phosphoglycerate, forming phosphoenolpyruvic acid (PEP).
In this step, 2 phosphoglycerate is changed into phosphoenolpyruvate (PEP) with the help of the enzyme enolase. Enolase works by removing a water group, or dehydrating the 2 phosphoglycerate. The enzyme's specific pocket allows the reaction to happen through a series of complex steps.
Step 10: Turning PEP into Pyruvate
In the final step, the enzyme pyruvate kinase helps change phosphoenolpyruvate (PEP) into pyruvate. This process involves moving a phosphate group from PEP to ADP, forming pyruvic acid and ATP in step 10.
The last part of glycolysis involves turning PEP into pyruvate, thanks to pyruvate kinase. As the enzyme's name implies, a phosphate group transfer takes place. The phosphate group connected to PEP's 2′ carbon is moved to an ADP molecule, creating ATP. Since there are two PEP molecules, we actually produce 2 ATP molecules in this step.
Steps 1 and 3: - 2ATP
Steps 7 and 10: + 4 ATP
Net visible ATP generated: 2.
Once glycolysis is complete, the cell needs to continue with either aerobic or anaerobic respiration, depending on its situation. A cell capable of aerobic respiration that has access to oxygen will proceed with the citric acid cycle inside the mitochondria. If a cell that can perform aerobic respiration doesn't have oxygen available (like muscles during intense exercise), it will switch to a kind of anaerobic respiration called homolactic fermentation. Some cells, like yeast, can't perform aerobic respiration and will automatically move into a form of anaerobic respiration known as alcoholic fermentation.
3 Steps to Learn Glycolysis (And never have to relearn it again)
These are the 3 steps I used to master the glycolysis pathway so I would never have to learn it again (woot woot).
STEP 1: Understand what Glycolysis actually does
Glycolysis is the process in which glucose is broken down to produce energy. It produces two molecules of pyruvate and ATP. The process takes place in the cytoplasm of a cell and does not require oxygen.
STEP 2: Draw a Diagram and Use Spaced Repetition to Master it
The Glycolysis By Axonious Concept map shows each step of Glycolysis. You can copy the map to get the corresponding spaced-repetitition flashcards. As you practice the glycolysis diagram over and over again you’ll remember how things connect.
STEP 3 (Connect Your Glycolysis Steps to other steps within Metabolism)
New material is retained better by connecting it to other points. Imagine how you can connect steps of Glycolysis to parts of the Kreb’s Cycle, or the Pentose Phosphate Pathway. Draw a Glycolysis flowchart to make those on paper, or in mind mapping software like Traverse. You’ll see that by making connections you’ll understand Glycolysis much better.
*Bonus Step (Create a Mnemonic)
I used a mnemonic to remember each enzyme of Glycolysis. What mnemonic could you create?
Get your copy of the Glycolysis diagram here (this will allow you to re-arrange, add notes and even create flashcards)
