Oxidative decarboxylation is a decarboxylation reaction caused by oxidation. Most are accompanied by α- Ketoglutarate α- Decarboxylation caused by dehydrogenation of hydroxyl carboxylic acids such as carbonyl carboxylic acid, malic acid, isocitric acid, etc.
Differences between oxidative decarboxylation and simple decarboxylation
Pyruvate catalytic reaction catalyzed by pyruvate dehydrogenase system is a special decarboxylation method, namely oxidative decarboxylation, which is different from the common decarboxylation reaction, namely common decarboxylation.
The oxidative decarboxylation reaction is catalyzed by pyruvate dehydrogenase system, which includes three different enzymes: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2), dihydrolipoamide dehydrogenase (E3), six cofactors: thiamine pyrophosphate (TPP), lipoamide, coenzyme A (CoA), flavin adenine dinucleotide (FAD), magnesium ion, and one co-substrate: nicotinamide adenine dinucleotide (NAD+).
During the reaction, E1 participates in the decarboxylation of pyruvic acid, and then TPP connects the acetyl group after the reaction. The carbonyl group of the acetyl group reacts with the carbonyl group of the carbon negative ion on the thiazole ring of TPP to form hydroxyethyl. Then, with the catalysis of E2, TPP sends the hydroxyethyl to lipoamide, which is reoxidized to acetyl to produce thioester bond. At this time, the compound is acetyl dihydrolipoamide, which is then catalyzed by E2, and acetyl is transferred, to form acetyl CoA, all the above reactions only involve decarboxylation reaction, and do not involve the movement of H, while the real dehydrogenation effect of pyruvate dehydrogenase system will be reflected in the next step of reaction. Acetyl dihydrolipoamide without acetyl group is lost, that is, dihydrolipoamide needs to be re oxidized to lipoamide to participate in the reaction again. At this time, E3 needs to participate in the catalytic reaction, and the hydrogen removed from dihydrolipoamide will be transferred to FAD to make it FADH2, FADH2 reacts with NAD+ to generate NADH and H+.
To sum up, in the oxidative decarboxylation reaction, there is both an oxidation reaction and a decarboxylation.
For simple decarboxylation reaction, the enzyme involved in this reaction is pyruvate decarboxylase, which is different from oxidative decarboxylation. During the reaction, pyruvate is directly connected with the thiazole ring of TPP, and the carboxyl group on pyruvate is removed after the connection to generate carbon dioxide. Then hydroxyethyl was separated from TPP to produce acetaldehyde.
Bridging glycolysis and the citric acid cycle
Pyruvate, the product of glycolysis under aerobic conditions, is a metabolic branch point. As a preliminary to following the central path of aerobic metabolism from glycolysis to the citric acid cycle, we put pyruvate in perspective by considering its various possible fates. We also consider the broader context of common carboxylation and decarboxylation reactions in biochemistry.
The most important fate of pyruvate at least for our present purposes is its oxidative decarboxylation to acetyl CoA, this reaction is catalyzed by a very large assembly of enzyme subunits called the pyruvate dehydrogenase complex (PDH complex, or often simply "PDH"). This large supramolecular assembly contains multiple copies of three different types of subunits. These subunits catalyze different steps of the overall reaction. Central to the operation of the PDH complex is a key catalytic cofactor, thiamine pyrophosphate (TPP). We will examine closely the chemistry of this extraordinary and important cofactor.
Carboxylation and decarboxylation reactions
Let us define a carboxylation reaction as the addition of a unit to a substrate molecule, and decarboxylation as loss of . Decarboxylation reaction reactions are typically quite thermodynamically favorable due to the entropic contribution of cleaving a single molecule into two, one of which is a gas. Conversely, we can expect carboxylation reactions to be energy-requiring, and we should not be surprised to learn ATP hydrolysis is coupled to carboxylation. The most prominent carboxylation reactions in biochemistry are catalyzed by biotin-dependent carboxylases and RuBisCO.
The biochemistry of thiamine
Decarboxylation in metabolism can be either non-oxidative or oxidative. In contrast to the relatively facile decarboxylation of β-keto acids, the decarboxylation of α-keto acids presents a mechanistic challenge. Thiamine pyrophosphate (TPP) provides the biochemical and enzymological answer.