We are now ready to begin going through the reactions of the citric acid
cycle. The cycle begins with the reaction between acetyl-CoA and the
four-carbon oxaloacetate to form six-carbon citric acid. Through the next
steps of the cycle, two of the six carbons of the citric acid leave as carbon
dioxide to ultimately yield the four carbon product, oxaloacetate, which is used
again in the first step of the next cycle. During the eight reactions that take
place, for every molecule of acetyl-CoA the cycle produces three NADH and
one flavin adenine dinucleotide (FAD/FADH2), along with one molecule of
ATP.
Figure %: The Citric Acid Cycle (Krebs Cycle).
Note: Students taking the AP test generally do not need to more about the
specifics of the citric acid cycle than what is contained in the above figure
and paragraph.
Reaction 1: Citrate Synthase
The first reaction of the citric acid cycle is catalyzed by the enzyme citrate
synthase. In this step, oxaloacetate is joined with acetyl-CoA to form citric
acid. Once the two molecules are joined, a water molecule attacks the acetyl
leading to the release of coenzyme A from the complex.
Figure %: Reaction 1.
Reaction 2: Acontinase
The next reaction of the citric acid cycle is catalyzed by the enzyme
acontinase. In this reaction, a water molecule is removed from the citric
acid and then put back on in another location. The overall effect of this
conversion is that the –OH group is moved from the 3' to the 4' position on the
molecule. This transformation yields the molecule isocitrate.
Figure %: Reaction 2.
Reaction 3: Isocitrate Dehydrogenase
Two events occur in reaction 3 of the citric acid cycle. In the first reaction,
we see our first generation of NADH from NAD. The enzyme isocitrate
dehydrogenase catalyzes the oxidation of the –OH group at the 4' position
of isocitrate to yield an intermediate which then has a carbon dioxide molecule
removed from it to yield alpha-ketoglutarate.
Figure %: Reaction 3.
Reaction 4: Alpha-ketoglutarate deydrogenase
In reaction 4 of the citric acid cycle, alpha-ketoglutarate loses a carbon
dioxide molecule and coenzyme A is added in its place. The decarboxylation
occurs with the help of NAD, which is converted to NADH. The enzyme that
catalyzes this reaction is alpha-ketoglutarate dehydrogenase. The mechanism
of this conversion is very similar to what occurs in the first few steps of
pyruvate metabolism. The
resulting molecule is called succinyl-CoA.
Figure %: Reaction 4.
Reaction 5: Succinyl-CoA Synthetase
The enzyme succinyl-CoA synthetase catalyzes the fifth reaction of the
citric acid cycle. In this step a molecule of guanosine triphosphate (GTP) is
synthesized. GTP is a molecule that is very similar in its structure and
energetic properties to ATP and can be used in cells in much the same way. GTP
synthesis occurs with the addition of a free phosphate group to a GDP molecule
(similar to ATP synthesis from ADP). In this reaction, a free phosphate group
first attacks the succinyl-CoA molecule releasing the CoA. After the phosphate
is attached to the molecule, it is transferred to the GDP to form GTP. The
resulting product is the molecule succinate.
