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DENF 1521 Biochemistry

Dental Biochemistry

Lesson 3.1 Glycolysis Overview

3.1 An Overview of Glycolysis

3.1A Lesson objectives

The objectives of this lesson are to understand that:

1. Glycolysis is the process of converting glucose into pyruvate
2. Small amounts of ATP are produced
3. Glycolysis occurs under anaerobic conditions
4. The pyruvate produced enters the citric acid cycle under aerobic conditions

3.1B Historical considerations

Glycolysis is a metabolic pathway found universally in biological systems. It is the metabolic pathway which converts glucose via a series of reactions to 2 molecules of pyruvate. As a result of these reactions, a small amount of ATP and NADH are produced. Most of the metabolic energy derived from glucose comes from the entry of pyruvate into the citric acid cycle and oxidative phosphorylation. These pathways occur under aerobic conditions and will be discussed in lessons 4 and 5. Under anaerobic conditions, pyruvate can be converted to lactate in muscle or ethanol in yeast.

Among the important findings determined as part of the elucidation of the glycolytic pathway were:

• The finding by Hans Buchner and Eduard Buchner that fermentation, the conversion of sucrose to ethanol, could occur in the absence of a living cell.
• The finding of a hexose di-phosphate intermediate in glycolysis
• The activities required for the reactions to occur were composed of a heat-labile, non-dialyzable substance (enzymes) and a heat-stable, dialyzable substance (coenzymes).
• Many scientists, including Gustav Embden, Otto Meyerhof, Carl Neuberg, Jacob Parnas, Otto Warburg, Gerty Cori, and Carl Cori, contributed to the complete determination of the pathway.
• Glycolysis is also known as the Embden-Meyerhof Pathway.

The following diagram summarizes the breakdown of glucose and some of its metabolic fates. Remember that lactate and ethanol are products of anaerobic conditions, while carbon dioxide and water require aerobic conditions to be produced.

Some of the metabolic fates of glucose

Dental Biochemistry

Lesson 3.1 Glycolysis overview

Glycolysis introduction
Practice Exercise 1:	One of the products of the metabolism of glucose under anaerobic conditions is lactate. No Response True False
Practice Exercise 2:	The major function of the glycolytic pathway is to No Response Produce carbon dioxide Directly produce most of the ATP needed by the cell Produce glucose Convert glucose to pyruvate

Dental Biochemistry

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Lesson 3.1 Glycolysis Overview

3.1C Key structures and reactions involved in metabolic pathways

Many of the structures and reactions which occur as part of the glycolytic pathway are also found in other forms in other metabolic pathways. Therefore, it is important to understand these structures and reactions before proceeding. The glycolytic pathway converts a 6-carbon molecule (glucose) into two interchangeable 3-carbon intermediate compounds which are then converted to pyruvate. All of the structures involved in glycolysis contain either 6- or 3-carbons. See lesson 2.1 to review carbohydrate structures.

The 6-carbon molecules are derivatives of

• glucose
• fructose

The 3-carbon molecules are derivatives of

• dihydroxyacetone
• glyceraldehyde
• glycerate
• pyruvate

All of the derivatives of these molecules are phosphorylated. The phosphoryl group is in either of 2 linkages, as shown below.

Ester
Anhydride

The 5 major reaction types which occur in glycolysis, as well as other metabolic pathways, are listed below.
Reaction Type	Enzyme Type	Chemistry involved
1. Phosphoryl transfer	Kinase	Transfer of phosphoryl group from ATP
2. Phosphoryl shift	Mutase	Shift of phosphoryl group from oxygen within molecule
3. Isomerization	Isomerase	Ketose converted to aldose or vice versa
4. Dehydration	Dehydrogenase	Elimination of water
5. Aldol cleavage	Aldolase	Split of carbon-carbon bond

Dental Biochemistry

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Lesson 3.1 Glycolysis Overview

Glycolysis Introduction
Practice Exercise 3:	The enzyme which catalyzes the transfer of a phosphoryl group from ATP to another compound is called a(n) No Response Mutase Kinase Aldolase Dehydrogenase
Practice Exercise 4:	Which of the following is NOT a 3 carbon compound which is part of the glycolytic pathway? No Response Fructose Dihydroxyacetone Glyceraldehyde Pyruvate

Dental Biochemistry

Lesson 3.1 Glycolysis Overview

3.1D The initial steps of glycolysis

Glycolysis takes place in the cytoplasm of the cell. The goal of the initial reactions of glycolysis is to convert glucose into fructose 1,6-bisphosphate. This traps glucose in the cell as glucose 6-phosphate and forms a phosphorylated compound (fructose 1,6-bisphosphate) that can be cleaved into phosphorylated 3-carbon intermediates. These 3-carbon units can then be used to generate ATP by the citric acid cycle and oxidative phosphorylation..

phosphorylated 3 carbon units

The first step in glycolysis is the phosphorylation of glucose by ATP to form glucose 6-phosphate. This reaction, catalyzed by the enzyme hexokinase, traps glucose in the cell.

The second step in glycolysis is the isomerization of glucose 6-phosphate to fructose 6-phosphate. This converts the sugar from a 6-membered pyranose to the 5-membered furanose structure and involves the converion of an aldose into a ketose. This reaction is catalyzed by the enzyme phosphoglucose isomerase.

The third step in glycolysis is a second phosphorylation to form fructose 1,6-bisphosphate catalyzed by the enzyme phosphofructokinase. Phosphofructokinase is an allosteric enzyme controlled by ATP and other metabolites. The importance of the control of phosphofructokinase will be discussed in a later lesson.

Dental Biochemistry

Lesson 3.1 Glycolysis Overview

Dental Biochemistry

Lesson 3.1 Glycolysis Overview

3.1D Stage II--The formation of 3-carbon units

Up to this point no energy in the form of ATP has been generated by glycolysis. Two ATP's have been used. The second stage of glycolysis involves the cleavage of the 6-carbon fructose 1,6-bisphosphate to 3-carbon sugars followed by isomerizations. The generation of 3-carbon units from the 6-carbon sugar is catalyzed by the enzyme aldolase. In this reaction, dihydroxyacetone phosphate and glyceraldehyde 3-phosphate are generated. The glyceraldehyde 3-phosphate generated in this reaction can continue directly in the glycolytic pathway. Dihydroxyacetone phosphate must be converted to glyceraldehyde 3-phosphate in order to continue in the pathway. This isomerization is catalyzed by the enzyme triose phosphate isomerase. At equilibrium most of the 3-carbon sugar is in the form of dihydroxyacetone phosphate. However, the removal of glyceraldehyde 3-phosphate in further glycolytic reactions allows the formation of more glyceraldehyde 3-phosphate from dihydroxyacetone phosphate.

The next reaction of glycolysis generates a high potential phosphorylated compound, 1,3-bisphosphoglycerate. This compound is formed from glyceraldehyde 3-phosphate by the action of the enzyme glyceraldehyde 3-phosphate dehydrogenase. In this reaction, inorganic phosphate (P_i) is incorporated into the C-1 position forming an acyl phosphate with NAD⁺ serving as the electron acceptor. The high energy potential of 1,3-bisphosphoglycerate is used to form ATP from ADP and P_i. This reaction is carried out by phosphoglycerate kinase. The 2 reactions diagrammed below result in the formation of NADH and ATP.

3.1E Formation of Pyruvate

The last part of glycolysis involves the formation of pyruvate and another molecule of ATP. This is accomplished by a rearrangement of 3-phosphoglycerate to form 2-phosphoglycerate followed by a dehydration to form phosphoenolpyruvate (PEP). The final nearly irreversible reaction is the formation of ATP and pyruvate catalyzed by the enzyme pyruvate kinase.

Dental Biochemistry

Lesson 3.1 Glycolysis Overview

Dental Biochemistry

Lesson 3.1 Glycolysis Overview

3.1F Summary

After completing this lesson you should understand the following about the glycolytic pathway.

1. The overall function of glycolysis is to convert glucose into 2 molecules of pyruvate.
2. Small amounts of ATP are produced
3. Glycolytic intermediates are used as building blocks for other metabolic pathways
4. Glycolysis occurs in the cell's cytoplasm under anaerobic conditions
5. The pyruvate produced enters the citric acid cycle under aerobic conditions