Chapter 6, Problem 2CP

Summary Introduction

To determine: The main events that occur during glycolysis.

Introduction: Glycolysis is a series of 10 enzyme-catalyzed reactions where one molecule of glucose is converted to two molecules of pyruvate. In this process, the total production of 2 ATP molecules and the reduction of 2 NAD⁺ to 2 NADH molecules occur.

Explanation of Solution

The main events that occur during glycolysis are as follows:

In Reaction 1 of glycolysis, a phosphoryl group is transferred from ATP to glucose to form glucose-6-phosphate (G6P) in a catalytic reaction that is continued by hexokinase. In this reaction, kinase acts as an enzyme that transfers the phosphoryl groups between ATP and a metabolite. The metabolite serves as the phosphoryl group acceptor.

Reaction 1: $\text{Glucose}\stackrel{\text{hexokinase}}{\to }\text{Glucose-6-phosphate}$

Reaction 2 of glycolysis explains the conversion of glucose-6-phosphate (G6P) and fructose-6-phosphate (F6P) in the presence of phosphoglucose isomerase (PGI). This reaction represents isomerization of an aldose to a ketone.

Reaction 2: $\text{Glucose-6-phosphate}\stackrel{\text{phosphoglucose}\text{isomerase}}{\rightleftharpoons }\text{Fructose-6-phosphate}$

In Reaction 3 of glycolysis, phosphofructokinase (PFK) phosphorylates fructose-6-phosphate (F6P) to form fructose-1,6-bisphosphate (FBP).

Reaction 3:  $\text{Fructose-6-phosphate}\stackrel{\begin{array}{c}\text{phosphofructokinase}\text{(PFK)}\\ {\text{Mg}}^{\text{2+}}\end{array}}{\to }\text{Fructose-1,6-bisphosphate}$

In Reaction 4 of the glycolysis pathway, aldolase catalyzes the cleavage of fructose-1,6-bisphosphate to form the two trioses, namely, glyceraldehyde-3-phosphate (GAP) and dihydroxyacetone phosphate. This represents the carbon–carbon cleavage that occurs in retro-aldol condensation. The cleavage occurs in-between C3 and C4 of fructose-1,6-bisphosphate.

Reaction 4:

$\begin{array}{l}\text{Fructose-1,6-bisphosphate}\stackrel{\text{aldolase}}{\rightleftharpoons }\text{Dihydroxyacetone}\text{phosphate}\text{(DHAP)}\\ \text{+}\\ \text{Glyceraldehyde-3-phosphate}\text{(GAP)}\end{array}$

Reaction 5 represents the products of the aldol cleavage reaction, where glyceraldehyde-3-phosphate is converted to dihydroxyacetone phosphate. In this reaction, interconversion occurs by an isomerization reaction with an enediol intermediate. Triose phosphate isomerase catalyzes this process in this reaction of glycolysis.

Reaction 5:

$\text{Glyceraldehyde-3-phosphate}\text{(GAP)}\rightleftharpoons \text{Enediol}\text{intermediate}\rightleftharpoons \text{Dihydroxyacetone}\text{phosphate}$

Reaction 6 of glycolysis represents the oxidation and phosphorylation of glyceraldehyde-3-phosphate (GAP) in the presence of NAD+ and Pi as catalyzed by glyceraldehyde-3-phosphate dehydrogenase to form 1,3-Bisphosphoglycerate.

Reaction 6:

$\text{Glyceraldehyde-3-phosphate}{\text{(GAP)+NAD}}^{\text{+}}{\text{+P}}_{\text{i}}\stackrel{\begin{array}{l}\text{glyceraldehyde-3-phosphate}\\ \text{dehydrogenase}\text{(GAPDH)}\end{array}}{\rightleftharpoons }\text{1,3-Bisphosphoglycerate}\text{(1,3-BPG)}$

Reaction 7 of the glycolysis pathway yields ATP with 3-phosphoglycerate (3GP) in a reaction that is catalyzed by the enzyme phosphoglycerate kinase (PGK). In this reaction, reverse phosphorylation occurs in the presence of kinase. From 1,3-Bisphosphoglycerate, one phosphate group is transferred to 3-phosphoglycerate (3GP) and ATP.

Reaction 7:

$\text{1,3-Bisphosphoglycerate}\text{(1,3-BPG)+ATP}\stackrel{\begin{array}{l}\text{phosphoglycerate}\\ \text{kinase}\text{(PGK)}\end{array}}{\rightleftharpoons }\text{3-Phosphoglycerate}\text{(3PG)+ATP}$

Reaction 8 of glycolysis represents the conversion of 3-phosphoglycerate (3PG) to 2-phosphoglycerate in the presence of phosphoglycerate mutase. This reaction also represents the isomerization reaction.

Reaction 8: $\text{3-Phosphoglycerate}\text{(3PG)}\stackrel{\begin{array}{l}\text{phosphoglycerate}\\ \text{mutase}\text{(PGM)}\end{array}}{\rightleftharpoons }\text{2-phosphoglycerate(2PG)}$

Reaction 9 of glycolysis explains the dehydration reaction in which 2-phosphoglycerate is dehydrated to phosphoenolpyruvate (PEP) in a reaction that is catalyzed by enolase.

Reaction 9: $\text{2-phosphoglycerate(2PG)}\stackrel{\text{enolase}}{\rightleftharpoons }\text{Phosphoenolpyruvate}{\text{(PEP)+H}}_{\text{2}}\text{O}$

In the final reaction, Reaction 10 of glycolysis, pyruvate kinase enhances phosphoenolpyruvate in the presence of ADP to form pyruvate and ATP. The pyruvate kinase reaction is highly exergonic such that it gives more energy to drive ATP synthesis, a substrate-level phosphorylation reaction.

Reaction 10: $\text{Phosphoenolpyruvate}{\text{(PEP)+ADP+H}}^{\text{+}}\stackrel{\text{pyruvate}\text{kinase}\text{(PK)}}{\to }\text{Pyruvate+ATP}$