Oxidative Decarboxylation of Pyruvic Acid | Biochemistry

In this article we will discuss about the oxidative decarboxylation of pyruvic acid.

We know that anaerobiosis the pyruvic acid formed during glycolysis reacts with NADH which accumulates to give lactic acid (or ethanol) and thus permits the regeneration of NAD⁺. But when oxygen is available, NADH is reoxidized thanks to the electrons carrier system, and the pyruvic acid is completely oxidized to CO₂ + H₂O.

This total oxidation takes place thanks to the Krebs cycle, but to enter this cycle, pyruvic acid must be first converted into acetyl-coenzyme A; we will now examine this transformation. It proceeds in several steps (see fig. 4-36), catalyzed by a multi-enzymatic complex called “pyruvate oxidase” or “pyruvate decarboxylase”.

Decarboxylation Reaction:

The coenzyme implied in this first step is thiamine pyrophosphate on which pyruvic acid attaches itself to be decarboxylated to acetaldehyde.

CH₃ — CO — COOH + E₁—TPP → CO₂ + E₁ – TPP – CH₃CHO

Oxidation Reaction:

The acetaldehyde thus activated reacts with lipoic acid, coenzyme in oxidized form (or disulphide): acetaldehyde is oxidized and linked in the form of a thio-ester to lipoic acid which is reduced (as a matter of fact, the thio-ester formed is the derivative of a di-thiol)

Formation of Acetyl Coenzyme A:

The acetyl group is transferred to another compound which carries a sulphydryl group — coenzyme A — thus forming acetyl coenzyme A and reduced lipoic acid (or dihydrolipoic acid).

The Reoxidation of Lipoic Acid:

Dihydrolipoate dehydrogenase, a FAD enzyme, catalyzes the reoxidation of lipoic acid in its disulphide form.

The Reoxidation of FADH:

E₃ – 2FADH + NAD⁺ → E₃ – 2 FAD + NADH + H⁺

As for the reoxidation of NADH, it takes place in aerobiosis thanks to the electrons carrier system, thus permitting the formation of 3 molecules of ATP.

The overall reaction of the oxidative decarboxylation of pyruvic acid can be written as in figure 4-37.

The advantage of oxidative decarboxylation is twofold: on the one hand, it permits — through the electron carrier system — the production of 3 molecules of ATP per molecule of pyruvic acid transformed. On the other hand, it leads to the formation of an activated acetyl group, which can be transferred to the oxaloacetic acid and thus enter the Krebs cycle.

As a matter of fact, the reactivity of the thio-ester group of acetyl-coenzyme A is comparable with that of acyl-phosphates (∆G₀ of the hydrolysis of acetyl-coenzyme A≠ -9 kcal/mole see table). The sulphydryl group of the molecule of coenzyme A (its complete structure is represented in figure 2-18) constitutes the reactive part of the molecule and is implied in the “acetyl” transfer reactions; for this reason, one generally writes: “coenzyme A-SH” or “C_oA-SH”.

The letter “A” indicates that it is a coenzyme acting in the transfer reactions of the Acetyl group. Having thus designated this coenzyme, it was also found that it acts not only in the metabolism of acetic acid but also in that of fatty acids in general.