24.10.

2013

Citric Acid Cycle Reactions

Citric Acid Cycle

Carbohydrate
Metabolism
Overview

Form Acetyl CoA

Citric Acid Cycle

Summary

Citric Acid Cycle

Reactions

Hormone Control

Overview
Metabolism &
Energy Summary

Elmhurst College

Cori Cycle

Chemistry Department
Virtual ChemBook

Citric Acid Cycle Reactions

Introduction:
Under aerobic conditions the end product of glycolysis is
pyruvic acid. The next step is the formation of acetyl
coenzyme A(acetyl CoA) - this step is technically not a part of
the citric acid cycle, but is shown on the diagram on the top left.
Acetyl CoA, whether from glycolysis or the fatty acid spiral, is
the initiator of the citric acid cycle. In carbohydrate metabolism,
acetyl CoA is the link between glycolysis and the citric acid
cycle.
The initiating step of the citric acid cycle occurs when a four
carbon compound (oxaloacetic acid) condenses with acetyl
CoA (2 carbons) to form citric acid (6 carbons).
The whole purpose of a "turn" of the citric acid cycle is to
produce two carbon dioxide molecules. This general oxidation
reaction is accompanied by the loss of hydrogen and electrons
at four specific places. These oxidations are connected to the
electron transport chain where many ATP are produced.
Click for larger image

The reactions for the citric acid cycle are shown in the graphic
on the left. These reactions are more familiar than those from
glycolysis. Unless the instructor states otherwise, you should
study these reactions so that you can: tabulate the ATP and
CO2 generated; name the type of reaction at each step; and
write the structure of any compound which has been blanked
out. You should not memorize these structures but derive them
from a knowledge of reaction principles.
Citric Acid Cycle - with white background for printing
Overview of Metabolism

Reaction 1: Synthesis of Citric Acid

Acetyl CoA and oxaloacetic acid condense to form citric acid.
The acetyl group CH3COO is transferred from CoA to
oxaloacetic acid at the ketone carbon, which is then changed to
an alcohol. The net effect is to join a 2 carbon piece with a 4
carbon piece to make citric acid which is 6 carbons. This is just
called the synthesis of citric acid.
This reaction is catalyzed by citric acid synthetase.
Reaction 1 - Chime in new window
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Citric Acid Cycle Reactions

Link to Chime: Citric Acid Synthetase - Department of

Biochemistry,The University of Arizona

Reaction 2: Dehydration of an alcohol

Two steps (Rx. 2 and 3) are required to isomerize the position
of the -OH group on citric acid. This first step is a dehydration
of an alcohol to make an alkene. The cis-aconitic acid remains
bound to the enzyme aconitase in readiness for the next step.
This reaction is catalyzed by aconitase.
Reaction 2 - Chime in new window
Reaction 3: Hydration to make alcohol
This reaction is a hydration reaction of an alkene to make an
alcohol. This hydration does not follow Markovnikov's Rule.
The net effect of reactions 2 and 3 has been to move the -OH
group from C-3 to C-2, which is isocitric acid.
This reaction is catalyzed by aconitase.
Reaction 3 - Chime in new window
Link to Chime: Aconitase - Department of Biochemistry,The
University of Arizona

Reaction 4: Oxidation
This is the first oxidation reaction in which an alcohol is
converted to a ketone. Two hydrogens and 2 electrons are
transferred to NAD+ to NADH + H+. This is the entry point
into the electron transport chain.
The product of this reaction, oxalosuccinic acid, remains
attached to the isocitrate dehydrogenase for the next step.
This reaction is catalyzed by isocitrate dehydrogenase.
Reaction 4 Chime in new window

Reaction 5: Decarboxylation
This is the first step where a carbon group is lost as carbon
dioxide in a decarboxylation reaction. The remaining compound
now has 5 carbons and is called alpha-ketoglutaric acid.
This reaction is also catalyzed by isocitrate dehydrogenase.
Reaction 5 Chime in new window
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Citric Acid Cycle Reactions

Reaction 6: Oxidation, Decarboxylation, Thiol Ester

Synthesis
This complex oxidative decarboxylation is guided by three
enzymes in much the same fashion as the formation of acetyl
CoA from pyruvic acid. This is actually the only non-reversible
step in the entire cycle and prevents the cycle from operating in
the reverse direction.
This is the second oxidation reaction in which an alcohol is
converted to a ketone. Two hydrogens and 2 electrons are
transferred to NAD+ to NADH + H+. This another the entry
point into the electron transport chain.
This is the second step where a carbon group is lost as carbon
dioxide in a decarboxylation reaction. Essentially, although not
the exact same carbons, the two carbons from the acetyl CoA
have been converted to carbon dioxide at the end this step/.
The remaining 4 carbon group is attached to the CoA through a
thiol ester high energy bond. Notice that the final product,
succinyl CoA, has 4 carbons in the succinate group at one end
of the CoA molecule.
This reaction is catalyzed by alpha-ketoglutarate dehydrogenase
complex.
Reaction 6 Chime in new window
Reaction 7: Hydrolysis of Succinyl CoA;
Synthesis of ATP
The hydrolysis of the thioester bond (exothermic) is coupled
with the formation of ATP (Actually guanosine triphosphate is
formed first but is further coupled with the ADP to make ATP).
This is the only "visible" ATP formed in the entire cycle.
Succinic acid, a 4 carbon acid, is the product of this reaction.
This is the start of the return to the beginning of the cycle.
This reaction is catalyzed by succinyl CoA.
Reaction 7 Chime in new window
Reaction 8: Oxidation
This slightly unusual oxidation reaction results in the removal of
the hydrogens from saturated alkyl carbons to form an alkene,
fumaric acid. The hydrogen acceptor is the coenzyme FAD
instead of the more usual NAD+. This will be significant when
the ATP is tabulated from the electron transport chain, since this
coenzyme is in the enzyme complex 2. Only 2 ATP result from
this reaction in the electron transport chain.
This reaction is catalyzed by succinate dehydrogenase.
Reaction 8 Chime in new window
Link to Chime: Succinate dehydrogenase - Department of
Biochemistry,The University of Arizona
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Reaction 9: Hydration to form an alcohol

This is a simple hydration reaction of an alkene to form an
alcohol. Take your pick where you place the -OH group since it
must be adjacent to a carboxylic acid group in either case and
forms malic acid.
This reaction is catalyzed by fumarase.
Reaction 9 - phosphoenol pyruvic acid Chime in new window
Reaction 10: Oxidation
This is the final reaction in the citric acid cycle. The reaction is
the oxidation of an alcohol to a ketone to make oxaloacetic
acid. The coenzyme NAD+ causes the transfer of two
hydrogens and 2 electrons to NADH + H+. This is a final entry
point into the electron transport chain.
This reaction is catalyzed by malate dehydrogenase.
Reaction 10 Chime in new window
Conclusion:
Starting with acetyl Co A with 2 carbons, the citric acid cycle
spins these 2 carbons off as two carbon dioxide molecules.

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