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Glycolysis
Stage 1: Glucose Breakdown
Glycolysis involves nine distinct reactions that convert glucose into pyruvate. In this section, we will cover the first four of these reactions, which convert glucose into glyceraldehyde-3-phosphate. Glucose is a six- memebered ring molecule found in the blood and is usually a result of the breakdown of carbohydrates into sugars. It enters cells through specific transporter proteins that move it from outside the cell into the cell's cytosol. All of the glycolytic enzymes are found in the cytosol.
Step 1: Hexokinase
In the first step of glycolysis, the glucose ring is phosphorylated. Phosphorylation is the process of adding a phosphate group to a molecule derived from ATP. As a result, at this point in glycolysis, 1 molecule of ATP has been consumed.
Figure %: Step 1.
The reaction occurs with the help of the enzyme hexokinase, an enzyme that catalyzes the phosphorylation of many six-membered glucose-like ring structures. A kinase is the name given to an enzyme that phosphorylates other molecules. Atomic magnesium (Mg) is also involved to help shield the negative charges from the phosphate groups on the ATP molecule. The result of this phosphorylation is a molecule called glucose-6-phosphate (G6P), thusly called because the 6' carbon of the glucose acquires the phosphate group.
Step 2: Phosphoglucose Isomerase
The second step of glycolysis involves the conversion of glucose-6-phosphate to fructose-6-phosphate (F6P). This reaction occurs with the help of the enzyme phosphoglucose isomerase (PI). As the name of the enzyme suggests, this reaction involves an isomerization reaction.
Figure %: Step 2.
The reaction involves the rearrangement of the carbon-oxygen bond to transform the six-membered ring into a five-membered ring. To rearrangement takes place when the six-membered ring opens and then closes in such a way that the first carbon becomes now external to the ring.
Step 3: Phosphofructokinase
In the third step of glycolysis, fructose-6-phosphate is converted to fructose- 1,6- bi sphosphate (FBP). Similar to the reaction that occurs in step 1 of glycolysis, a second molecule of ATP provides the phosphate group that is added on to the F6P molecule.
Problems
Problem : Where does glycolysis take place in a cell? In the cytosol.
Problem : What is the name of the enzyme that catalyzes the phosphorylation of a glucose molecule in the first step of glycolysis? Hexokinase.
Problem : In glycolytic steps one and three, what is the source of the phosphate groups that are added to glucose and fructose-6-phosphate, respectively?
enzyme that catalyzes this reaction is glyceraldehyde-3-phosphate dehydrogenase (GAPDH).
Figure %: Step 5.
The chemistry that takes place in this reaction is more complex than that of the previous reactions we've discussed. Knowledge of organic chemistry is needed to understand the specific mechanisms of the conversion. Generally, the enzyme GAPDH contains appropriate structures and holds the molecule in a conformation such that it allows the NAD molecule to pull a hydrogen off the GAP, converting the NAD to NADH. The phosphate group then attacks the GAP molecule and releases it from the enzyme to yield 1,3 bisphoglycerate, NADH, and a hydrogen atom. We will come back to the role of this NAD/ NADH molecule in the next section. Step 6: Phosphoglycerate Kinase
In this step, 1,3 bisphoglycerate is converted to 3-phosphoglycerate by the enzyme phosphoglycerate kinase (PGK). This reaction involves the loss of a phosphate group from the starting material. The phosphate is transferred to a molecule of ADP that yields our first molecule of ATP. Since we actually have two molecules of 1,3 bisphoglycerate (because there were two 3-carbon products from stage 1 of glycolysis), we actually synthesize two molecules of ATP at this step. With this synthesis of ATP, we have cancelled the first two molecules of ATP that we used, leaving us with a net of 0 ATP molecules up to this stage of glycolysis.
Figure %: Step 6.
Again, we see that an atom of magnesium is involved to shield the negative charges on the phosphate groups of the ATP molecule.
Step 7: Phosphoglycerate Mutase
This step involves a simple rearrangement of the position of the phosphate group on the 3 phosphoglycerate molecule, making it 2 phosphoglycerate. The molecule responsible for catalyzing this reaction is called phosphoglycerate mutase (PGM). A mutase is an enzyme that catalyzes the transfer of a functional group from one position on a molecule to another.
Figure %: Step 7.
The reaction mechanism proceeds by first adding an additional phosphate group to the 2' position of the 3 phosphoglycerate. The enzyme then removes the phosphate from the 3' position leaving just the 2' phosphate, and thus yielding 2 phsophoglycerate. In this way, the enzyme is also restored to its original, phosphorylated state.
Step 8: Enolase
The eighth step involves the conversion of 2 phosphoglycerate to phosphoenolpyruvate (PEP). The reaction is catalyzed by the enzyme enolase. Enolase works by removing a water group, or dehydrating the 2 phosphoglycerate. The specificity of the enzyme pocket allows for the reaction to occur through a series of steps too complicated to cover here.
Figure %: Step 8.
Step 9: Pyruvate Kinase
Problem : What two types of reactions does glyceraldehyde-3-phosphate dehydrogenase catalyze in the fifth step of glycolysis? Glyceraldehyde-3-phosphate dehydrogenase first oxidizes and then phosphorylates glyceraldehyde-3-phosphate.
Problem : What is the name of the enzyme that catalyzes the reaction that converts 1,3 bisphoglycerate to 3-phosphoglycerate? Phosphoglycerate kinase.
Problem : How many molecules of ATP are produced during the second stage of glycolysis? There are four ATP molecules are produced during the second stage of glycolysis. They are produced in steps six and nine.
Problem : What role does atomic magnesium play in step 6 of glycolysis involving the conversion of 1,3 bisphoglycerate to 3-phosphoglycerate? Magnesium functions to shield the negative charges that are abundant on the ATP molecule as a result of its phosphate groups.
Problem : What general name is given to an enzyme that catalyzes the transfer of a functional group from one position on a molecule to another? A mutase.
