Chapter 17

Glycolysis

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Chapter Outline
(17-1) The overall pathway of glycolysis
(17-2) Conversion of six-carbon glucose to three-carbon
glyceraldehyde-3-phosphate
(17-3) Glyceraldehyde-3-phosphate is converted to pyruvate
(17-4) Anaerobic metabolism of pyruvate
(17-5) Energy production in glycolysis
(17-6) Control of glycolysis

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Glycolysis
• First stage of glucose metabolism in organisms
• One molecule of glucose is converted to fructose-1,6-
bisphosphate, which gives rise to two molecules of
pyruvate
• Plays a key role in the way organisms extract energy
from nutrients
• Anaerobic glycolysis
• Pathway of conversion of glucose to lactate
• Distinguished from glycolysis, which is the conversion
of glucose to pyruvate

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Figure 17.1 - One Molecule of Glucose Is
Converted to Two Molecules of Pyruvate

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Figure 17.3 - Glycolytic Pathway

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Reactions of Glycolysis
• Phosphorylation of glucose to give glucose-6-
phosphate
• Isomerization of glucose-6-phosphate to give
fructose-6-phosphate
• Phosphorylation of fructose-6-phosphate to yield
fructose-1,6-bisphosphate
• Cleavage of fructose-1,6-bisphosphate to give two 3-
carbon fragments, glyceraldehyde-3-phosphate and
dihydroxyacetone phosphate
• Isomerization of dihydroxyacetone phosphate to give
glyceraldehyde-3-phosphate

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Reactions of Glycolysis (continued)
• Oxidation of glyceraldehyde-3-phosphate to give 1,3-
bisphosphoglycerate
• Transfer of a phosphate group from 1,3-
bisphosphoglycerate to ADP to give 3-
phosphoglycerate
• Isomerization of 3-phosphoglycerate to give 2-
phosphoglycerate
• Dehydration of 2-phosphoglycerate to give
phosphoenolpyruvate
• Transfer of a phosphate group from
phosphoenolpyruvate to ADP to give pyruvate

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Figure 17.4 - Conversion of Glucose to
Glyceraldehyde-3-Phosphate

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Figure 17.5 - Chemical Structure Changes Associated with the
Conversion of Glucose to Glyceraldehyde-3-Phosphate

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Conversion of Six-Carbon Glucose to
Three-Carbon Glyceraldehyde-3-
Phosphate
• Glucose is phosphorylated to give glucose-6-
phosphate
• Phosphorylation is endergonic as it is driven by the
free energy of hydrolysis of ATP
• Catalyzed by hexokinase

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Figure 17.8 - Comparison of the Conformations of
Hexokinase and the Hexokinase–Glucose Complex

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Conversion of Six-Carbon Glucose to Three-
Carbon Glyceraldehyde-3-Phosphate (continued 1)
• Glucose-6-phosphate isomerizes to give fructose-6-
phosphate
• Catalyzed by glucose phosphate isomerase
• C-1 aldehyde group of glucose-6-phosphate is
reduced to a hydroxyl group
• C-2 hydroxyl group is oxidized to give the ketone
group of fructose-6-phosphate, with no net oxidation or
reduction reaction

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Conversion of Six-Carbon Glucose to Three-
Carbon Glyceraldehyde-3-Phosphate (continued 2)
• Fructose-6-phosphate is further phosphorylated to
produce fructose-1,6-bisphosphate
• Phosphorylation of fructose-6-phosphate is coupled to
hydrolysis of ATP
• Phosphofructokinase
• Key allosteric control enzyme in glycolysis
• Catalyzes the phosphorylation of fructose-6-phosphate

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Figure 17.11 - Possible Isozymes of
Phosphofructokinase

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Conversion of Six-Carbon Glucose to Three-
Carbon Glyceraldehyde-3-Phosphate (continued 3)
• Fructose-1,6-bisphosphate is split into two three-
carbon fragments
• Aldolase: Enzyme that catalyzes the reverse aldol
condensation of fructose-1,6-bisphosphate
• Side chain of an essential lysine residue and the thiol
group of a cysteine play key roles in catalysis

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Conversion of Six-Carbon Glucose to Three-
Carbon Glyceraldehyde-3-Phosphate (continued 4)
• Dihydroxyacetone phosphate is converted to
glyceraldehyde-3-phosphate
• Triosephosphate isomerase: Enzyme that catalyzes
the conversion of dihydroxyacetone phosphate to
glyceraldehyde-3-phosphate
• Reaction has a +G value (+2.41 kJ mol-1 or +0.58 kcal
mol-1)
• Glycolysis has several reactions that have very
negative G values, driving reactions to completion
• Makes G values of the overall process negative

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Figure 17.14 - Conversion of Dihydroxyacetone
Phosphate into Glyceraldehyde-3-Phosphate

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Figure 17.15 - Second Phase of Glycolysis

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Figure 17.16 - Structural Depiction of the
Second Phase of Glycolysis Reactions

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Conversion of Glyceraldehyde-3-Phosphate
to Pyruvate
• Glyceraldehyde-3-phosphate is oxidized to 1,3-
bisphosphoglycerate
• Involves addition of a phosphate group and an electron
transfer
• Oxidizing agent, NAD+, is reduced to NADH

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Oxidation and Phosphorylation Reactions

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Figure 17.22 - Role of the Active Cysteine Residue in
Glyceraldehyde-3-Phosphate Dehydrogenase

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Conversion of Glyceraldehyde-3-Phosphate
to Pyruvate (continued 1)
• 1,3-bisphosphoglycerate is converted to 3-
phosphoglycerate
• Involves another reaction in which ATP is produced by
phosphorylation of ADP
• Catalyzed by phosphoglycerate kinase
• 1,3-bisphosphoglycerate transfers a phosphate group
to ADP, producing ATP
• Reaction is the sum of the endergonic phosphorylation
of ADP and the exergonic hydrolysis of the mixed
phosphate anhydride

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Figure 17.23 - Dephosphorylation of 1,3-
Bisphosphoglycerate to 3-Phosphoglycerate

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Conversion of Glyceraldehyde-3-Phosphate
to Pyruvate (continued 2)
• 3-phosphoglycerate isomerizes to give 2-
phosphoglycerate
• Catalyzed by phosphoglyceromutase

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Conversion of Glyceraldehyde-3-Phosphate
to Pyruvate (continued 3)
• 2-phosphoglycerate molecule loses one molecule of
water, producing phosphoenolpyruvate
• Enolase: Catalyzes the reaction and requires Mg2+ as
a cofactor
• Phosphoenolpyruvate contains a high-energy bond

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Conversion of Glyceraldehyde-3-Phosphate
to Pyruvate (continued 4)
• Phosphoenolpyruvate (PEP) transfers its phosphate
group to ADP, producing ATP and pyruvate
• G of hydrolysis of PEP is more negative than that of
ATP
• –61.9kJ mol-1 versus –30.5kJ mol-1
• Catalyzed by pyruvate kinase

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Anaerobic Metabolism of Pyruvate
• Under anaerobic conditions, the most important
pathway for the regeneration of NAD+ is reduction of
pyruvate to lactate
• Lactate dehydrogenase (LDH)
• NADH-linked dehydrogenase that catalyzes the
conversion of pyruvate to lactate
• Consists of M and H subunits
• H4 predominates in heart muscle and M4 in skeletal muscle

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Figure 17.29 - Recycling of NAD+ and NADH in
Anaerobic Glycolysis

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Production of Ethanol by Alcoholic Fermentation
• Decarboxylation of pyruvate to acetaldehyde
• Pyruvate decarboxylase
• Enzyme involved in the catalysis
• Requires Mg2+ and a cofactor, thiamine pyrophosphate
(TPP)
• Reduction of acetaldehyde to ethanol
• Alcohol dehydrogenase: Enzyme that catalyzes the
conversion of acetaldehyde to ethanol

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Figure 17.31 - Structures of Thiamine (Vitamin B1) and Thiamine
Pyrophosphate (TPP), the Active Form of the Coenzyme

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Figure 17.32 - Mechanism of the Pyruvate
Decarboxylase Reaction

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Energy Production in Glycolysis
• Glycolysis is exergonic
• G°′ from glucose to two pyruvates is equal to –74.0
kJ mol–1
• Energy released in the exergonic phases of the
process drives the endergonic reactions
• Phosphorylation is involved as two moles of ADP are
converted to ATP
• Energy released by glycolysis serves no purpose for
the organism without the production of ATP to serve
as a source of energy for other metabolic processes

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Table 17.1 - Reactions of Glycolysis and Their
Standard Free-Energy Changes

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Figure 17.36 - Control Points in Glycolysis

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Figure 17.37 - Control of Liver Pyruvate Kinase
by Phosphorylation

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