Carbohydrate Overview

Citric Acid Cycle Metabolism Metabolism & Elmhurst College

Overview Energy Summary
Citric Acid Cycle
Form Acetyl CoA Cori Cycle Chemistry Department
Summary
Citric Acid Cycle
Hormone Control Virtual ChemBook
Reactions

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

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

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
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.