After emerging from glycolysis, the two pyruvate are transported into the
mitochondria. There, the
pyruvate undergo a transition stage before entering the actual citric acid
cycle. In this phase the pyruvate is transformed into acetyl-coenzyme A
(acetyl-CoA), the starting product in the citric acid cycle. ;
2 Pyruvate + 2 coenzyme A + 2NAD+ -> 2 acetyl-CoA +2CO2 +
2 NADH
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Formation of Acetyl-CoA
Acetyl-CoA is a common product of carbohydrate, lipid, and protein
breakdown. It consists of an acetyl group attached to a coenzyme A
molecule. Coenzyme A is a large molecule that contains a molecule of ADP with
two side chain groups stemming from its phosphate arms. Acetyl groups attach to
the end of these side chains. In this way, the coenzyme A acts as a carrier of
acetyl groups. When it is broken down by water, large amounts of energy are
released, which, as we shall see, drive the citric acid cycle. The most common
way that acetyl-CoA is derived in the metabolic pathway is with the help of the
pyruvate dehydrogenase multienzyme complex.
The pyruvate dehydrogenase multienzyme is a complex of three distinct enzymes
that together convert pyruvate into acetyl-CoA with the help of a molecule of
coenzyme A and NAD. The mechanism for the formation of acetyl-CoA is complex,
as seen below. Generally, in reaction 1, the enzyme
pyruvate dehydrogenase pulls a carbon dioxide molecule off the pyruvate.
This is accomplished with the help of a molecule called TPP that forms a
temporary bond with the pyruvate molecule. The carbon dioxide removal reaction
is similar to that of the yeast pyruvate decarboxylase in
alcoholic
fermentation.
Figure 1.1: Pyruvate Metabolism to form Acetyl-CoA.
In reaction 2, the enzyme dihydrolipoyl transacetylase helps to attach
another temporary molecule called a lipoamide. With this bond formation, the
TPP molecule from the first step is released leading to the formation of an
acetyl group. In the third step, this lipoamide group is reduced and released
as a molecule of CoA attacks the acetyl group. We now have acetyl-CoA.
The third enzyme, dihydrolipoyl dehydrogenase, is responsible for restoring
the lipoamide to its original, oxidized state so that it can be reused in the
cycle in a fourth step. The molecule of NAD asserts itself at this point,
helping to reoxidize the lipoamide.
At this point, we have acetyl-CoA and are ready to enter the citric acid cycle.
