Glycolysis is the first step in the breakdown of glucose to extract energy for cellular metabolism. Glycolysis consists of an energy-requiring phase followed by an energy-releasing phase.
Suppose that we gave one molecule of glucose to you and one molecule of glucose to Lactobacillus acidophilus—the friendly bacterium that turns milk into yogurt. What would you and the bacterium do with your respective glucose molecules?
Overall, the metabolism of glucose in one of your cells would be pretty different from its metabolism in Lactobacillus—check out the fermentation article for more details. Yet, the first steps would be the same in both cases: both you and the bacterium would need to split the glucose molecule in two by putting it through glycolysis.
What is glycolysis?
Glycolysis is a series of reactions that extract energy from glucose by splitting it into two three-carbon molecules called pyruvates. Glycolysis is an ancient metabolic pathway, meaning that it evolved long ago, and it is found in the great majority of organisms alive today.
In organisms that perform cellular respiration, glycolysis is the first stage of this process. However, glycolysis doesn’t require oxygen, and many anaerobic organisms—organisms that do not use oxygen—also have this pathway.
Highlights of glycolysis
Glycolysis has ten steps, and depending on your interests—and the classes you’re taking—you may want to know the details of all of them. However, you may also be looking for a greatest hits version of glycolysis, something that highlights the key steps and principles without tracing the fate of every single atom. Let’s start with a simplified version of the pathway that does just that.
Glycolysis takes place in the cytosol of a cell, and it can be broken down into two main phases: the energy-requiring phase, above the dotted line in the image below, and the energy-releasing phase, below the dotted line.
- Energy-requiring phase. In this phase, the starting molecule of glucose gets rearranged, and two phosphate groups are attached to it. The phosphate groups make the modified sugar—now called fructose-1,6-bisphosphate—unstable, allowing it to split in half and form two phosphate-bearing three-carbon sugars. Because the phosphates used in these steps come from , two molecules get used up.
The three-carbon sugars formed when the unstable sugar breaks down are different from each other. Only one—glyceraldehyde-3-phosphate—can enter the following step. However, the unfavorable sugar, , can be easily converted into the favorable one, so both finish the pathway in the end
- Energy-releasing phase. In this phase, each three-carbon sugar is converted into another three-carbon molecule, pyruvate, through a series of reactions. In these reactions, two molecules and one molecule are made. Because this phase takes place twice, once for each of the two three-carbon sugars, it makes four and two overall.
Each reaction in glycolysis is catalyzed by its own enzyme. The most important enzyme for regulation of glycolysis is phosphofructokinase, which catalyzes formation of the unstable, two-phosphate sugar molecule, fructose-1,6-bisphosphate. Phosphofructokinase speeds up or slows down glycolysis in response to the energy needs of the cell.
Overall, glycolysis converts one six-carbon molecule of glucose into two three-carbon molecules of pyruvate. The net products of this process are two molecules of ( produced used up) and two molecules of .
Detailed steps: Energy-requiring phase
We’ve already seen what happens on a broad level during the energy-requiring phase of glycolysis. Two s are spent to form an unstable sugar with two phosphate groups, which then splits to form two three-carbon molecules that are isomers of each other.
Next, we’ll look at the individual steps in greater detail. Each step is catalyzed by its own specific enzyme, whose name is indicated below the reaction arrow in the diagram below.
Step 1. A phosphate group is transferred from to glucose, making glucose-6-phosphate. Glucose-6-phosphate is more reactive than glucose, and the addition of the phosphate also traps glucose inside the cell since glucose with a phosphate can’t readily cross the membrane.
Step 2. Glucose-6-phosphate is converted into its isomer, fructose-6-phosphate.
Step 3. A phosphate group is transferred from to fructose-6-phosphate, producing fructose-1,6-bisphosphate. This step is catalyzed by the enzyme phosphofructokinase, which can be regulated to speed up or slow down the glycolysis pathway.
Step 4. Fructose-1,6-bisphosphate splits to form two three-carbon sugars: dihydroxyacetone phosphate () and glyceraldehyde-3-phosphate. They are isomers of each other, but only one—glyceraldehyde-3-phosphate—can directly continue through the next steps of glycolysis.
Step 5. is converted into glyceraldehyde-3-phosphate. The two molecules exist in equilibrium, but the equilibrium is “pulled” strongly downward, in the scheme of the diagram above, as glyceraldehyde-3-phosphate is used up. Thus, all of the is eventually converted.
Detailed steps: Energy-releasing phase
In the second half of glycolysis, the three-carbon sugars formed in the first half of the process go through a series of additional transformations, ultimately turning into pyruvate. In the process, four molecules are produced, along with two molecules of .
Here, we’ll look in more detail at the reactions that lead to these products. The reactions shown below happen twice for each glucose molecule since a glucose splits into two three-carbon molecules, both of which will eventually proceed through the pathway.
Step 6. Two half reactions occur simultaneously: 1) Glyceraldehyde-3-phosphate (one of the three-carbon sugars formed in the initial phase) is oxidized, and 2) is reduced to and . The overall reaction is exergonic, releasing energy that is then used to phosphorylate the molecule, forming 1,3-bisphosphoglycerate.
Step 7. 1,3-bisphosphoglycerate donates one of its phosphate groups to , making a molecule of and turning into 3-phosphoglycerate in the process.
Step 8. 3-phosphoglycerate is converted into its isomer, 2-phosphoglycerate.
Step 9. 2-phosphoglycerate loses a molecule of water, becoming phosphoenolpyruvate (). is an unstable molecule, poised to lose its phosphate group in the final step of glycolysis.
Step 10. readily donates its phosphate group to , making a second molecule of . As it loses its phosphate, is converted to pyruvate, the end product of glycolysis.
What happens to pyruvate and ?
At the end of glycolysis, we’re left with two , two , and two pyruvate molecules. If oxygen is available, the pyruvate can be broken down (oxidized) all the way to carbon dioxide in cellular respiration, making many molecules of . You can learn how this works in the videos and articles on pyruvate oxidation, the citric acid cycle, and oxidative phosphorylation.
What happens to the ? It can't just sit around in the cell, piling up. That's because cells have only a certain number of molecules, which cycle back and forth between oxidized () and reduced () states:
Glycolysis needs to accept electrons as part of a specific reaction. If there’s no around (because it's all stuck in its form), this reaction can’t happen and glycolysis will come to a halt. So, all cells need a way to turn back into to keep glycolysis going.
There are two basic ways of accomplishing this. When oxygen is present, can pass its electrons into the electron transport chain, regenerating for use in glycolysis. (Added bonus: some gets made!)
When oxygen is absent, cells may use other, simpler pathways to regenerate . In these pathways, donates its electrons to an acceptor molecule in a reaction that doesn’t make but does regenerate so glycolysis can continue. This process is called fermentation, and you can learn more about it in the fermentation videos.
Fermentation is a primary metabolic strategy for lots of bacteria—including our friend from the introduction, Lactobacillus acidophilus. Even some cells in your body, such as red blood cells, rely on fermentation to make their .
Want to join the conversation?
- Why the 1st phase are same in aerobic and anaerobic respiration(4 votes)
- This is because oxidation in glycolysis doesn't involve oxygen atoms. It's just movement of hydrogen. So it's behaving in the same way with or without oxygen.(83 votes)
- when NAD is turned into NADH, G3P(5H) loses two electrons and "two" protons. but in the next step, 3-bis..., theres still 4H. not sure how this happens.(16 votes)
- In the Investment phase, where did the 2 atps come from that were used up? was it taken from somewhere else? if the goal is to produce atp in glycilysis, where do we get atp to begin the process?(7 votes)
- The ATPs originally came from your mother through parental nutrition, while you where developing in the womb. When you are born you will have a stock pile of ATP in your body, which must be replenished to stay alive. The body has many ways to make ATP, which can be seen by looking at the vast amount of metabolic reactions that occur with the body. This is also why we can survive for a long time without any additional consumption of food as the many catabolism pathways in the body that breakdown larger molecules and transfer the energy from the breakdown to ATP. When food is abundant the breakdown of glucose by glycolysis and the Krebs cycle will produce much more ATP than the 2 ATPS required in the investment phase. Additionally, this investment phase aids in regulating the metabolic reactions that occur in our body/cells.(26 votes)
- In the highlight glycolysis part,in the second last paragraph,why fructose-1,6-bisphosphate is unstable?
Can you explained more detail on what is means by speeds up or slows down glycolysis?I still dont understand.
Thank you.(4 votes)
- One important note is that the enzyme that catalyzes the reaction phosphofructosekinase is what actually speeds up or slow downs glycolysis. Once fructose-1,6-bisphosphate is formed it will be broken down to the two carbon molecules at the same speed. The way it is speed up or slowed down is due to phosphofructosekinase the enzyme that catalyzes the reaction to create fructose-1,6-bisphosphate is regulated by both ATP and ADP, when ATP levels are high it is inhibited and less fructose-1,6-bisphosphate will be created when ADP levels are high it will be activated and more fructose-1,6-bisphosphate will be created. This allows the cells a way to regulate the breakdown of glucose depending on the energy needs of the cell as stated by Chris.(10 votes)
- In step 6, where does the second phosphate group come from?(5 votes)
- By my understanding, phosphates are often freely floating throughout the cell. This is because they're used for tons of processes, and enzymes like phosphatase clip them off of ATP and various other molecules during reactions, and then just leave them to float around.(2 votes)
- what is the difference between aerobic and anaerobic glycolysis?(2 votes)
- Aerobic is within an oxygen filled environment. and anaerobic there is no oxygen present in the environment.(7 votes)
- in step 6 in the detailed payoff phase... how after NAD+ is reduced, gained 2 H+ and converted to NADH, H+ is still produced ?
Thanks in advance.(4 votes)
- I think you have two very subtle differences mixed. Note that one H radical is [H]+ with one electron, and the reason why I write this is because when you add the proton, the H+, then you actually also need to add additional electrons, so for every one H you also have one electron. You would write:
1. The NAD+ gains 2H (free radical) to become NADH (free radical) & [H]+.
2. Alternatively, you could say that the NAD gains 2H (free radical) to give NADH2 (free radical)(6 votes)
- What is unusual about fructose being metabolized in the liver vs other tissue types?(3 votes)
- There are several reasons. Simply put, the liver is really well equipped and prepared to metabolise it and also fructose, as opposed to glucose for example, seems to be a better substrate for glycogen synthesis in the liver.
Fructose and glucose both seem to be very similar, they have almost identical structures but even a tiny change in a molecule can affect how it is metabolised in the body. I recommend reading up on it further since that's a fascinating question worth exploring.(3 votes)
- The steps 5&6 are confusing me
In step 4 the aldolase enzyme break up the "Fructose-1,6-phosphate" into GAP & DHAP
What's after that ?
without structures please.(3 votes)
- DHAP gets converted to G3P (glyceraldehyde-3-phosphate) by the enzyme triosephosphate isomerase and then you get 2 G3P molecules which get converted to 1, 3 bisphosphoglycerate by glyceraldahyde-3-phosphate dehydrogenase and at the same time you have 2 NAD+ being reduced to 2 NADH by a hydrogen ion and 2e- going to each NAD+(3 votes)
- Is this substrate-level phosphorylation?(3 votes)
- True. Substrate level phosphorylation (physical addition of phosphate to the ADP and building ATP) can happen during glycolysis and TCA in the matrix of mitochondria.
This paper contrasts substrate phosphorylation and oxidative phosphorylation: