The 10 Reactions That Turn Glucose Into Energy | Glycolysis

Introduction

0:00This lovely dog gets a portion of chicken broth every day, full of tons of proteins and sugars. Among these sugars is one very special one, glucose, the key piece that kicks off one of the most important metabolic pathways of all, glycolysis. Most living things, from animals to plants and bacteria, are carrying out glycolysis all the time.

0:27This is doing glycolysis. And so is this. And yes, even this is doing glycolysis. And of course, the cells in your body are also hard at work. Right now, as you listen, they're busy breaking down glucose through glycolysis to produce energy.

History: from Embden to Parnas

0:48Let me tell you a bit about how this pathway was discovered. In the early 20th century, research into how cells obtained energy from glucose was moving forward rapidly. Gustav Embden, in the early 1910s and 1920s, was one of the first to uncover the key steps of the process in muscle cells.

1:08His work revealed several reactions in the breakdown of glucose, laying the groundwork for what would later become glycolysis. Otto Meyerhof, working in the 1920s, dug deeper into the relationship between lactic acid metabolism and oxygen consumption in muscle, showing how energy was produced under anaerobic conditions.

1:28In 1922 he received the Nobel Prize in Physiology or Medicine for his discoveries about muscle metabolism. Finally, Jakub Karol Parnas, in the 1930s, contributed detailed studies of the enzymes that regulate glycolysis, rounding out the scheme of the metabolic pathway. Together, their work gave rise to what is now known as the Embden-Meyerhof-Parnas pathway, or simply glycolysis.

What glycolysis is

1:54But now let's get to the important part. What is glycolysis? As you might guess, "glyco" comes from the word glucose, the sugar found in many foods, and "lysis" means breakdown or splitting. So there you have it, glycolysis is a metabolic pathway in which glucose is broken down to generate energy. Let me introduce you to glycolysis, and even though it may look complicated, don't be afraid of it, because I'm here to walk you through all the details.

2:21It has 10 reactions, each one very important, and the final product of this whole tangle of reactions is pyruvate, remember that well. The first five reactions are known as the investment phase or preparatory phase, since this is where one ATP, or adenosine triphosphate, is spent in the first reaction, and another in the third reaction.

Energy investment phase (reactions 1-5)

2:41If you're not quite clear on what ATP is, you can picture it as a battery that can be charged and discharged. When the cell needs energy, it discharges a molecule of adenosine triphosphate, converting it into adenosine diphosphate. Just look at the difference between the two molecules. ATP has three phosphates and ADP has only two.

3:02The last five reactions are known as the payoff phase or generation phase, since here not only are the ATPs invested in the first phase recovered, but two brand-new ones are also generated, leaving us with a net gain of two ATPs for every molecule of glucose that goes through this pathway. Glycolysis takes place in the cytoplasm of cells and doesn't require oxygen to occur, which is why even anaerobic organisms, such as certain bacteria, are able to put glycolysis to use.

3:30It's time to walk you through the reactions that make up this pathway one by one. In the first reaction, glucose is converted into glucose 6-phosphate by the enzyme hexokinase, which uses magnesium as a cofactor. This reaction requires energy in the form of ATP, which is used to add a phosphate group to glucose.

3:51Next, glucose 6-phosphate is converted by the enzyme phosphoglucose isomerase into fructose 6-phosphate. Fructose 6-phosphate is converted into fructose 1,6-bisphosphate by the action of the enzyme phosphofructokinase 1, or PFK1, which also uses magnesium as a cofactor.

4:12This reaction also requires an ATP. Here, the cell commits to moving forward with glycolysis, since PFK1 regulates the rate of the process. Fructose 1,6-bisphosphate is split into two three-carbon molecules, dihydroxyacetone phosphate, or DHAP, and glyceraldehyde 3-phosphate, or G3P, through the action of the enzyme fructose bisphosphate aldolase.

4:36Only glyceraldehyde 3-phosphate can continue on in glycolysis, so dihydroxyacetone phosphate is converted into glyceraldehyde 3-phosphate by the enzyme triose phosphate isomerase, allowing both molecules to move forward through the pathway. Now we have two molecules of glyceraldehyde 3-phosphate, so the second phase runs twice for every glucose broken down in the pathway.

Energy payoff phase (reactions 6-10)

4:59Glyceraldehyde 3-phosphate is converted into 1,3-bisphosphoglycerate by the enzyme glyceraldehyde 3-phosphate dehydrogenase, or GAPDH, in a reaction that generates reduced NAD from oxidized NAD. 1,3-bisphosphoglycerate is converted into 3-phosphoglycerate by the enzyme phosphoglycerate kinase, and this is where ATP is produced.

5:19Since there are two molecules of 1,3-bisphosphoglycerate, two ATPs are generated in this step. The enzyme phosphoglycerate mutase converts 3-phosphoglycerate into 2-phosphoglycerate, moving the phosphate group from one carbon to another. 2-phosphoglycerate is dehydrated by the enzyme enolase, producing phosphoenolpyruvate, or PEP, a high-energy molecule.

5:42In the last reaction, phosphoenolpyruvate is converted into pyruvate thanks to the enzyme pyruvate kinase, which generates two more molecules of ATP and two molecules of pyruvate, one for each phosphoenolpyruvate. In glycolysis there are three enzymes considered the most important, due to their key role in the pathway's irreversible reactions, and also because they're highly regulated.

Enzymatic regulation

6:05These enzymes are hexokinase, which is inhibited by glucose 6-phosphate, its own product, preventing cells from continuing to take up and phosphorylate glucose once they already have enough. Phosphofructokinase 1, or PFK1, is inhibited when ATP levels are high, since that means the cell doesn't need more energy production, preventing an unnecessary expenditure of glucose.

6:28It's also inhibited by high levels of citrate, a precursor of the Krebs cycle, because that's a way of signaling to the cell that it has enough energy precursors. It's activated when there are high levels of adenosine monophosphate or adenosine diphosphate, which indicate low energy in the cell. This promotes glycolysis and energy generation.

6:49It's also activated by fructose 2,6-bisphosphate. This is an allosteric regulator that increases the activity of PFK1, ensuring that glycolysis stays active even when ATP levels aren't critically low. Pyruvate kinase is inhibited by ATP, for the same reason as PFK1. It's activated by fructose 1,6-bisphosphate through a feed-forward mechanism, promoting the continuation of glycolysis once fructose 1,6-bisphosphate has been produced in the earlier steps of the pathway.

7:19Finally, it can also be regulated through hormones such as insulin, which activates pyruvate kinase, while glucagon inactivates it. Now that you know the 10 reactions of glycolysis, you might be wondering: is that all it does? Well, no. Glycolysis doesn't just convert glucose into pyruvate, it also produces key intermediates for other essential metabolic pathways.

Connections with other metabolic pathways

7:42For example, glucose 6-phosphate, the first product of glycolysis, can be diverted into the pentose phosphate pathway, where it generates reduced NADP, needed for lipid biosynthesis and antioxidant defense, and ribose-5-phosphate, crucial for the synthesis of DNA and RNA. 3-phosphoglycerate can be used to form the amino acids serine and glycine, which are essential for protein synthesis.

8:08Cofactors such as the reduced NAD generated in glycolysis are essential for the electron transport chain, helping to produce more ATP in the mitochondria or taking part in oxidation-reduction reactions elsewhere in the cell. Pyruvate, for its part, has several routes available: it can be converted into alanine through transamination, it can be fermented to form lactate or ethanol under anaerobic conditions, or it can be transformed into acetyl coenzyme A, a key molecule that feeds the Krebs cycle to generate more energy, or it can be used for fatty acid synthesis.

8:41Ever since you were a baby you were already an expert at doing glycolysis, but now you're even able to understand it. Funny how life works, isn't it? That's all for today's video. I'm Suppah, and don't forget to do your glycolysis. Bye.