Download 23.1 The Citric Acid Cycle

Lecture Presentation
Chapter 23
Metabolism and
Energy
Production
Karen C. Timberlake
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Chapter 23 Metabolism and Energy Production
Exercise physiologists work with
athletes as well as patients who
have been diagnosed with
diabetes, heart disease,
pulmonary disease, or other
chronic disabilities or diseases.
Often these patients have been
prescribed exercise as a form of
treatment, and they have been
referred to an exercise
physiologist.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Chapter 23 Readiness
Core Chemistry Skills
• Writing Equations for Hydrogenation, Hydration,
and Polymerization (12.7)
• Classifying Enzymes (20.2)
• Identifying Important Coenzymes in Metabolism
(22.2)
• Identifying the Compounds in Glycolysis (22.4)
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
23.1 The Citric Acid Cycle
The citric acid cycle is
a series of reactions
that connects the
intermediate acetyl CoA
from the catabolic
pathways in stage 2
with electron transport
and the synthesis of
ATP in stage 3.
Learning Goal Describe the oxidation of acetyl CoA in the
citric acid cycle.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
23.1 The Citric Acid Cycle
The citric acid cycle (stage 3)
• operates under aerobic conditions.
• oxidizes the two-carbon acetyl group in acetyl CoA to CO2.
• produces reduced coenzymes NADH and FADH2.
• is named for the six-carbon citrate ion from citric acid
(C6H8O7), a tricarboxylic acid, formed in the first reaction.
• is also known as the tricarboxylic acid (TCA) cycle or the
Krebs cycle.
Core Chemistry Skill Describing the Reactions in the Citric
Acid Cycle
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Citric Acid Cycle Overview
In the citric acid cycle,
• six carbons move through the citric acid cycle,
producing oxaloacetate and 2CO2.
• each turn contains four oxidation reactions
producing the reduced coenzymes NADH and
FADH2.
• one GTP (converted to ATP in the cell) is
produced during the citric acid cycle.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Citric Acid Cycle Overview
• In the citric acid cycle, eight
reactions oxidize acetyl CoA
from pyruvate or fatty acids,
producing CO2 and the highenergy compounds FADH2,
NADH, and GTP.
• Reactions involved in the
citric acid cycle include
condensation, dehydration,
hydration, oxidation,
reduction, and hydrolysis.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Stages of Catabolism
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Reaction 1: Formation of Citrate
In the first reaction of the citric acid cycle,
• citrate synthase catalyzes the condensation of an acetyl
group (2C) from acetyl CoA with oxaloacetate (4C) to yield
citrate (6C) and coenzyme A.
• the energy to form citrate is provided by the hydrolysis of
the high-energy thioester bond in acetyl CoA.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Reaction 2: Isomerization
In reaction 2 of the citric acid cycle,
• citrate rearranges to isocitrate, a secondary alcohol.
• aconitase catalyzes the dehydration of citrate (tertiary
alcohol) to yield cis-aconitate, followed by a hydration
that forms isocitrate (secondary alcohol).
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Reaction 3: Oxidation, Decarboxylation
In reaction 3, isocitrate undergoes decarboxylation by
isocitrate dehydrogenase.
• One carbon is removed by converting a carboxylate group
(COO−) to CO2.
• The dehydrogenase removes hydrogen ions and electrons,
used to reduce NAD+ to NADH and H+.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Reaction 4: Decarboxylation, Oxidation
In reaction 4, catalyzed by α-ketoglutarate dehydrogenase,
• α-ketoglutarate (5C) undergoes decarboxylation to yield
(4C) succinyl CoA.
• oxidation of the thiol group (— SH) in HS — CoA provides
hydrogen that is transferred to NAD+ to form a second
molecule of NADH and H+.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Reaction 5: Hydrolysis
In reaction 5, catalyzed by succinyl CoA synthetase,
• hydrolysis of the thioester bond in succinyl CoA yields
succinate and HS — CoA.
• energy from hydrolysis is transferred to the condensation of
phosphate and GDP forming GTP, a high-energy
compound similar to ATP.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Reaction 6: Hydrolysis
In reaction 6, catalyzed by succinate dehydrogenase,
• succinate is oxidized to fumarate, a compound with a
C = C bond.
• 2H lost from succinate are used to reduce the coenzyme
FAD to FADH2.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Reaction 7: Hydration
In reaction 7, catalyzed by fumarase, water is added
to the double bond of fumarate to yield malate, a
secondary alcohol.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Reaction 8: Oxidation
In reaction 8, catalyzed by malate dehydrogenase,
• the hydroxyl group in malate is oxidized to a carbonyl group,
yielding oxaloacetate.
• oxidation provides hydrogen ions and electrons for the
reduction of NAD+ to NADH and H+.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Summary, Citric Acid Cycle
In the citric acid cycle,
• an acetyl group bonds with oxaloacetate to form citrate.
• two decarboxylations remove two carbons as two CO2.
• four oxidations provide hydrogen for three NADH and one FADH2.
• a direct phosphorylation forms GTP (ATP).
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Regulation of the Citric Acid Cycle
The reaction rate for the
citric acid cycle
• increases when low
levels of ATP or NAD+
activate isocitrate
dehydrogenase.
• decreases when high
levels of ATP or NADH
inhibit citrate synthetase
(first step in cycle).
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Study Check
How many of each of the following are produced in
one turn of the citric acid cycle?
A. _ CO2
B. _ NADH
C. _ FADH2
D. _ GTP
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Solution
How many of each of the following are produced in
one turn of the citric acid cycle?
A. 2 CO2
B. 3 NADH
C. 1 FADH2
D. 1 GTP
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.