Glycolysis Part 1 – MCAT Biochemistry | MedSchoolCoach

Glycolysis Part 1

MCAT Biochemistry - Chapter 6 - Section 1.1 - Cellular Respiration - Glycolysis Part 1

Sample MCAT Question - Glycolysis Part 1

Which step in glycolysis is the first irreversible step unique to glycolysis? 

a) Isomerization of glucose 6-phosphate to fructose-6-phosphate

b) Conversion of DHAP to glyceraldehyde 3-phosphate

c) Cleavage of fructose-1,6-bisphosphate
d) Phosphorylation of fructose-6-phosphate

D is correct. Phosphorylation of fructose-6-phosphate.

The third step of glycolysis is the phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate. Not only is this step irreversible, but it is the first step unique to glycolysis. This is because the product of this step, fructose 1,6-bisphosphate, can only be used in glycolysis. Therefore, the phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate is the committed step for glycolysis. Answer choice A is incorrect, this is the second step in glycolysis and is reversible. Answer choice B is incorrect, this step is reversible. Answer choice D is incorrect as it is also reversible.

Glycolysis and Cellular Respiration

In order for cells to live and grow, they undergo cellular respiration. Cellular respiration is a series of biochemical processes inside cells in which nutrients are broken down into energy that can then be used to drive cellular reactions. In most cells, glucose is the primary molecule that is used. This is because glucose is a high energy molecule that can be oxidized to release energy.

 

C6H12O6 + 6 O2 → 6 CO2 + 6 H2O

The overall reaction of glucose oxidation is shown above and can be summarized as follows: one molecule of glucose reacts with six molecules of oxygen to produce six molecules of carbon dioxide and water. During this process, glucose is oxidized to carbon dioxide, and oxygen is reduced to water. This overall reaction takes place through several processes.The first of these processes is called glycolysis. Glycolysis is an evolutionarily conserved biochemical pathway that breaks glucose down into two molecules of pyruvate. This process releases energy that is stored in the form of ATP molecules and NADH molecules. 

 

(To see a summary of the glycolysis reaction as a whole, including the net products and reactants, click here. For a discussion of the reverse reaction, gluconeogenesis, where pyruvate is converted back into glucose, click here. And for details about how glycolysis and gluconeogenesis are regulated, see this post.)

 

Notably, while glucose breakdown does release some energy, there is still energy stored in the two pyruvate molecules. Therefore, in subsequent pathways (i.e. the decarboxylation of pyruvate by pyruvate dehydrogenase complex and the subsequent entry of acetyl-CoA into the Krebs cycle), these pyruvate molecules will also be broken down to continue to release even more energy to power cellular processes. But first, let’s look at glycolysis.

Preparatory Phase of Glycolysis

Glycolysis is a 10-step biochemical process that can be divided into two phases. This post covers the preparatory phase, which encompasses the first five steps of glycolysis. (Our post on the last five steps of glycolysis, the payoff phase, is located here.) 

 

The preparatory phase involves the breakdown of glucose into two molecules of glyceraldehyde-3-phosphate. This phase involves the consumption of two ATP molecules, as shown below in Figure 1.

Preparatory Phase of Glycolysis - MCAT Biochemistry
Figure 1. Preparatory Phase of Glycolysis

Step 1: Phosphorylation of Glucose

The first step of the preparatory phase is the phosphorylation of glucose (Figure 2). In this step, glucose is phosphorylated by hexokinase to form glucose 6-phosphate. This step is irreversible because the reaction is exergonic, meaning that it releases free energy. Moreover, the reaction is catalyzed by the enzyme hexokinase. A kinase is an important enzyme type to know for the MCAT exam. Kinases are transferases that, in this case of hexokinase, transfer a phosphate group from one molecule to another molecule. In this first step, hexokinase is transferring a phosphate group from ATP to glucose. It is essential to note the difference between kinases and phosphorylases. Phosphorylase enzymes add inorganic phosphate molecules to a molecule. Inorganic phosphates are free phosphate molecules sitting in solution that are not bound to any organic molecules.

Glycolysis Step 1: Glucose Phosphorylation - MCAT Biochemistry
Figure 2. Glycolysis Step 1: Glucose Phosphorylation

Step 2: Isomerization of Glucose-6-Phosphate

The next step in the preparatory phase is the isomerization of glucose 6-phosphate to fructose 6-phosphate (Figure 3). Glucose 6-phosphate is an aldose sugar, which means that it has an aldehyde functional group. Glucose 6-phosphate is converted to fructose 6-phosphate, which is a ketose sugar that has a ketone functional group. This step is an isomerization reaction that is catalyzed by the enzyme phosphohexose isomerase.

Glycolysis Step 2: Isomerization of Glucose-6-Phosphate - MCAT Biochemistry
Figure 3. Glycolysis Step 2: Isomerization of Glucose-6-Phosphate

Step 3: Phosphorylation of Fructose-6-Phosphate

The third step in glycolysis is the phosphorylation of fructose 6-phosphate (Figure 4). Fructose 6-phosphate is phosphorylated by phosphofructokinase-1 (PFK-1) into fructose 1,6-bisphosphate. This step is another irreversible step, as it is also exergonic and releases free energy. Moreover, this is the first committed step in the glycolytic pathway because it is the first irreversible step unique to glycolysis. Although the first step of glycolysis, the phosphorylation of glucose, is also irreversible, the product of that step, glucose 6-phosphate, feeds into multiple biochemical pathways (including, for instance, the pentose phosphate pathway. The product of this step, however, is only used in glycolysis.

Glycolysis Step 3: Phosphorylation of Fructose-6-Phosphate - MCAT Biochemistry
Figure 4. Glycolysis Step 3: Phosphorylation of Fructose-6-Phosphate

Also, in terms of nomenclature, it is important to note that molecules with two phosphate groups at two different positions are called bisphosphates. An example of a bisphosphate is fructose 1,6-bisphosphate, which is shown on the right of Figure 4 above. This molecule has two phosphate groups located on carbons 1 and 6, respectively.

 

Bisphosphates should not be confused with diphosphates. Diphosphates are molecules with two phosphate groups that are linked together. An example of a diphosphate is adenosine diphosphate, or ADP (Figure 5). ADP is a nucleotide that contains two phosphate groups linked together at carbon 5 of the sugar backbone. 

Adenosine Diphosphate - MCAT Biochemistry
Figure 5. Adenosine Diphosphate

Step 4: Cleavage of Fructose-1,6-Bisphosphate

The fourth step in the preparatory phase is the cleavage of fructose 1,6-bisphosphate (Figure 6). In this step, fructose 1,6-bisphosphate is cleaved into two molecules: glyceraldehyde 3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP). Both of these products are 3-carbon sugars, or triose sugars. This reaction is catalyzed by the enzyme aldolase.

Glycolysis Step 4: Cleavage of Fructose-1,6-Bisphosphate - MCAT Biochemistry
Figure 6. Glycolysis Step 4: Cleavage of Fructose-1,6-Bisphosphate

Step 5: Conversion of Triose Phosphate

The last step in the preparatory phase is the conversion of triose phosphates (Figure 7). In this step, DHAP is converted to G3P by the enzyme triose phosphate isomerase.

Glycolysis Step 5: Conversion of Triose Phosphate - MCAT Biochemistry
Figure 7. Glycolysis Step 5: Conversion of Triose Phosphate

The result of the preparatory phase is the production of two molecules of glyceraldehyde 3-phosphate from glucose. Also, as previously mentioned, this process expends two molecules of ATP. The second phase of glycolysis is called the payoff phase and is covered in this post.

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