Summary

This document provides a detailed explanation of glycolysis, a fundamental metabolic pathway in cells. It covers the process of converting glucose into pyruvate, the generation of ATP, and the role of enzymes. The text also touches on the sources of glucose in the diet and how glucose enters cells.

Full Transcript

There is a very good reason why we are looking at glycolysis first out of the many metabolic pathways possible; it is found in nearly all prokaryotic and eukaryotic cells! In eukaryotic cells, this pathway occurs in the cytosol, which means that as soon as glucose is transported into the cell, the e...

There is a very good reason why we are looking at glycolysis first out of the many metabolic pathways possible; it is found in nearly all prokaryotic and eukaryotic cells! In eukaryotic cells, this pathway occurs in the cytosol, which means that as soon as glucose is transported into the cell, the enzymes of glycolysis can immediately act on it. Glycolysis is the sequence of reactions that converts one molecule of glucose to two molecules of pyruvate. Glycolysis serves two major functions. First, it generates ATP. Second, a number of the intermediates of this pathway serve as building blocks for the biosynthesis of other biomolecules such as amino acids and fatty acids. We start, therefore, with this highly conserved metabolic pathway, for one cannot fully appreciate the other pathways we will look at unless one understands and appreciates the elegance of the glycolytic pathway and the central role it plays in metabolism. Before we talk about the details of this pathway, it is important that you see the ‘big picture”. The reason this pathway is so central is that it is involved in metabolizing glucose, which is a fuel used by almost all organisms. This pathway takes glucose, a 6-carbon molecule, and through a series of reactions converts it to two 3-carbon molecules of pyruvate. During this conversion, there are two ATP consumed in the first stage of the pathway, but then in the second stage of the pathway, there are a total of 4 ATP produced per molecule of glucose (2 ATP per 3-carbon molecule). Thus, glycolysis generates a net of 2 ATP per molecule of glucose. As we will see later, pyruvate can undergo further metabolism to generate a lot more ATP. It is worth taking a moment to discuss where most of the glucose comes from that enters our cells to start glycolysis. We actually eat very little free glucose; rather, most dietary carbohydrate is in the form of starch which is a polymer of glucose units linked together. We also get glucose from the digestion of lactose, which is the disaccharide found in milk; from the degradation of sucrose otherwise known as table sugar; and from the breakdown of maltose which is a product of starch breakdown and rich in foods where fermentation by yeast occurs such as in breads and brewed beverages. It should also be noted that glucose doesn’t just diffuse across the cell membrane to get into the cell; rather, there are specific transporters that assist in this process. In mammals, there are several types of glucose transporters that have different functions and as such are present in different tissues (Table 2-1). First step: phosphorylation of glucose – when glucose enters the cell, it is rapidly phosphorylated by hexokinase to form glucose-6-phosphate. This is the first step in glycolysis. This is a very important step since phosphorylation of glucose traps it in the cell and prevents it from being transported out. Note that kinases are enzymes that phosphorylate biomolecules using ATP as the phosphate donor. Humans have over 500 different kinases that perform the various phosphorylations of biomolecules that our cells require. This reaction is irreversible 2. In the next step, Glucose-6-P is converted to fructose-6-P: this is an isomerization reaction, meaning that there are no atoms lost, but only a rearrangement of the atoms occurs. In this case, it involves the conversion of an aldose to a ketose by phosphoglucose isomerase. This reaction is necessary because glucose-6-P is not readily cleaved into two 3-carbon fragments, while fructose-6-P is. Note that this is a reversible reaction 3. Fructose-6-P is phosphorylated at a second carbon to form fructose-1,6-bisphosphate: this irreversible reaction is catalyzed by phosphofructokinase which is regulated allosterically. This is an important regulatory step in glycolysis that we will revisit later 4. Cleavage of fructose 1,6-bisphosphate to two different 3-carbon molecules: In this step, fructose 1,6-bisphosphate is cleaved by aldolase to dihydroxyacetone phosphate and glyceraldehyde-3-phosphate The products of the remaining steps in glycolysis consist of 3-carbon units. At this stage, it is important to note that glyceraldehyde-3-P is the molecule that proceeds directly onward in the glycolytic pathway. However, dihydroxyacetone phosphate is not wasted or lost from the pathway, since it is readily converted to glyceraldehyde-3-P by an isomerase in a reversible reaction 5. Oxidation of glyceraldehyde-3-P powers the formation of 1,3-bisphosphogycerate which has high phosphoryl-transfer activity: In this step, 1,3-bisphosphoglycerate is generated by the oxidation of glyceraldehyde-3-P by the enzyme glyceraldehyde-3-P dehydrogenase. Note that dehydrogenases are enzymes that catalyze redox reactions The net result of this reaction is that the phosphate group is attached to a carboxylic acid group via a mixed acid anhydride bond. This has a high phosphoryl-transfer potential, and we will see in the next step that this phosphate group gets transferred to ADP to form ATP 6. Phosphoryl transfer from 1,3-bisphosphoglycerate to ADP to form ATP: This is the first energy producing step in glycolysis, and is catalyzed by phosphoglycerate kinase. ATP formed in this manner is termed substrate-level phosphorylation, since the donor of the phosphate group is a substrate in the reaction. We will contrast this with ATP formation from ionic gradients in a later module Remember that there are actually two ATPs formed at this step for every molecule of glucose started with, since one glucose generates two 3-carbon molecules that flow this pathway 7. 3-phosphoglycerate is converted to 2-phosphoglycerate by phosphoglycerate mutase. Mutases are isomerases that reposition phosphate groups within a molecule (see Figure 2-8). More ATP is formed as we get to the end of glycolysis: 2-phosphoglycerate is then converted to phosphoenolpyruvate (or PEP) by the enzyme enolase. PEP is a high phosphoryl-transfer compound, and is able to donate its phosphate group to ADP in the last step of glycolysis catalyzed by pyruvate kinase. This is another example of substrate-level phosphorylation Now that we have discussed all of the reactions of glycolysis, we can write the net reaction for the entire pathway: Glucose + 2 Pi +2 ADP + 2 NAD+ 2 pyruvate + 2 ATP + 2 NADH + 2 H+ + 2 H2O The individual reactions of glycolysis are shown in Table 2-2 below. Note that the overall free energy change is about -22 kcal/mol. Thus, while some individual reactions are reversible, glycolysis as a pathway only flows in one direction, that being towards the production of pyruvate Note that the pathway from glucose to pyruvate has no requirement for oxygen, which is why this is referred to as anaerobic glycolysis. We will see a bit later that much more energy can be obtained from glucose in the presence of oxygen as it allows further metabolism of pyruvate.

Use Quizgecko on...
Browser
Browser