Krebs Cycle

Krebs Cycle
Krebs Cycle
 It was named after the Hans
Adolf Krebs who discovered it in
1937.
 It is also known by several
other names:
 Citric Acid Cycle
 Tricarboxylic Acid Cycle (TCA)
 This cycle occurs in the mitochondrial matrix.
 It is the series of biochemical reactions in which the acetyl portion of acetyl

CoA is oxidized to carbon dioxide and the reduced coenzymes FADH2 and
NADH are produced.
 The Krebs cycle is known as Amphibolic, in that it is both catabolic (breaks

down molecules) and anabolic (builds molecules).
 It is a series of chemical reactions used by all aerobic organisms to generate

energy through the oxidization of acetate derived from carbohydrates, fats,
and proteins into carbon dioxide.
 Each stage in the cycle occurs twice for every glucose molecule that enters
glycolysis, because 2 pyruvate molecules are produced for each glucose.
 The eight steps of the citric acid cycle are a series of redox, dehydration,
hydration, and decarboxylation reactions.
 Each turn of the cycle forms one GTP or ATP as well as three NADH molecules
and one FADH2 molecule, which will be used in further steps of cellular
respiration to produce ATP for the cell.
Unlocking of Terms
Oxidation - removal of electrons from a molecule. This subsequently lowers the

energy content of a molecule.
 Most biological oxidations involve the loss of hydrogen atoms. This type of
oxidation is referred to as a dehydrogenation. The enzymes that catalyzes these
reactions are called dehydrogenases.
 Gain of oxygen atoms.

Reduction - opposite of oxidation. It is the addition of electrons to a molecule.
 When a molecule is oxidized, the liberated hyrdride ions (H-) do not remain
free in the cell. In order to harness the energy of these electrons, they are
immediately transferred to another compound by coenzymes.
 Loss of oxygen atom.

Phosphorylation - accomplished by transferring a phosphate group to ADP
Decarboxylation - carbon chain is shortened by the removal of a carbon atom

(COO-) as CO2
Isomerization - is the process by which one molecule is transformed into another

molecule which has exactly the same atoms
Dehydration - removing of water molecules
Hydration - addition of water molecules

Link Reaction between Glycolysis and Krebs
Cycle -Pyruvate conversion to Acetyl CoA
 Pyruvate is transported across the
mitochondrion’s inner membrane and
into the inner compartment, called the
matrix.
 An enzyme pyruvate dehydrogenase
complex splits each molecule of
pyruvate into a molecule of CO2 and
a two-carbon acetyl group.
 The CO2 diffuses out of the cell, and the acetyl group combines
with a molecule called coenzyme A (abbreviated as CoA). The
product of this reaction is acetyl-CoA.
 NAD+ is changed to its reduced form, NADH that will enter the
Electron Transport Chain.
Reactions of the Citric Acid Cycle
Step 1; Formation of Citrate
 Acetyl CoA, which carries the two-carbon degradation product of glycolysis

enters the cycle by combining with the oxaloacetate to give (S)- citryl CoA.
The addition is catalyzed by the citrate synthase.
 (S)-citryl CoA is hydrolyzed to citrate catalyzed by the same citrate synthase to

produce CoA-SH and citrate.
Step 2 ; Formation of Isocitrate
 Citrate, a tertiary alcohol, is converted into its isomer, isocitrate, a secondary
alcohol, in an isomerization process that involves dehydration followed by
hydration that are both catalysed by the enzyme aconitase.
 –OH group from citrate is moved to a different carbon atom.

Step 3 ; Oxidation of Isocitrate and
Formation of CO2
 This step involves oxidation-reduction (the first of four redox reactions in the Krebs Cycle)
and decarboxylation.
 The reaction catalyzed by isocitrate dehydrogenase is complex: (1) Isocitrate is oxidized to

oxalosuccinate by NAD+, releasing 2 hydrogen atoms. (2) One hydrogen and two electrons are
transferred to NAD+ to form NADH; the remaining hydrogen ion is released. (3) the
oxalosuccinate remains bound to the enzyme and undergoes decarboxylation, which produces
the 5-carbon species α-ketoglutarate.
 This step yields the first molecules of CO2 and NADH in the cycle.
Step 4 ; Oxidation
of α-ketoglutarate and Formation of CO2
 This second redox reaction of the cycle involves one molecule each of
NAD+, CoA-SH, and α-ketoglurate. •
 The catalyst is an aggregate of three enzymes called the α-ketoglutarate

dehydrogenase complex.
 Both redox reaction and decarboxylation occur.
 Three products: CO2, NADH, and the 4-carbon species succinyl CoA.
 This step yields the second molecule of CO2 and NADH in the cycle.
Did you know that???
• The CO2 molecules produced in steps 3 and 4

of the citric acid cycle are the CO2 molecules
we exhale in the process of respiration.
Step 5 ; Thioester bond cleavage in Succinyl CoA and
Phosphorylation of GDP
 Two molecules react with succinyl CoA—a molecule of GDP (similar to ADP)
and a free phosphate group (Pi).
 The enzyme succinyl CoA synthetase removes coenzyme A by thioester bond

cleavage.
 The energy released is used to combine GDP and Pi to give GTP.
 Succinyl CoA has been converted to succinate.

Step 6 ; Oxidation of Succinate
 This is the third redox reaction of the cycle.
 Succinate is dehydrogenated by FAD catalyzed by succinate

dehydrogenase to produce fumarate, a 4-carbon species with trans double
bond.
 FAD is reduced to FADH2.

Step 7 ; Hydration of Fumarate
 The enzyme fumarase catalyzes the addition of water (nucleophilic

addition) to the double bond of fumarate.
 The enzyme is stereospecific, so only the L-isomer of the product

malate is produced.
S tep 8 O; x id a tio n o fL -M a la teo R eg en era teO x a lo a ceta te
 This is the fourth redox reaction of the cycle.
 A molecule of NAD+ reacts with malate, picking up two hydrogen atoms

(oxidation) with the associated energy to form NADH + H+.
 This reaction is catalyzed by malate dehydrogenase.
 The product of this reaction, is oxaloacetate that can combine with another
molecule of Acetyl CoA, and the cycle can begin again.

Krebs Cycle

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Krebs Cycle

 It is the series of biochemical reactions in which the acetyl portion of acetyl

 The Krebs cycle is known as Amphibolic, in that it is both catabolic (breaks

 It is a series of chemical reactions used by all aerobic organisms to generate

Oxidation - removal of electrons from a molecule. This subsequently lowers the

 Gain of oxygen atoms.

 Loss of oxygen atom.

Decarboxylation - carbon chain is shortened by the removal of a carbon atom

Isomerization - is the process by which one molecule is transformed into another

Dehydration - removing of water molecules

Hydration - addition of water molecules

 Acetyl CoA, which carries the two-carbon degradation product of glycolysis

 (S)-citryl CoA is hydrolyzed to citrate catalyzed by the same citrate synthase to

 –OH group from citrate is moved to a different carbon atom.

 The reaction catalyzed by isocitrate dehydrogenase is complex: (1) Isocitrate is oxidized to

 The catalyst is an aggregate of three enzymes called the α-ketoglutarate

 Both redox reaction and decarboxylation occur.

• The CO2 molecules produced in steps 3 and 4

 The enzyme succinyl CoA synthetase removes coenzyme A by thioester bond

 The energy released is used to combine GDP and Pi to give GTP.

 Succinyl CoA has been converted to succinate.

 This is the third redox reaction of the cycle.

 Succinate is dehydrogenated by FAD catalyzed by succinate

 FAD is reduced to FADH2.

 The enzyme fumarase catalyzes the addition of water (nucleophilic

 The enzyme is stereospecific, so only the L-isomer of the product

 This is the fourth redox reaction of the cycle.

 A molecule of NAD+ reacts with malate, picking up two hydrogen atoms

 This reaction is catalyzed by malate dehydrogenase.

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