How is pyruvate converted to acetyl-CoA? (2023)

How many enzymes are needed to convert pyruvate to acetyl-CoA?

How pyruvate is converted to acetyl-CoA

Pyruvate can come from a number of sources, including glycolysis, as we've seen. It migrates from the cytosol to the mitochondria by a specific transporter. There an enzyme system is calledPyruvate Dehydrogenase Complexit is responsible for converting pyruvate into carbon dioxide and the acetyl portion of acetyl-CoA. At one end of the CoA molecule is a -SH group where this is the casewhich acetyl group is attached. As a result, CoA is often shown as CoA-SH in equations. Because CoA is a thiol (the sulfur [thio] analog of an alcohol), acetyl-CoA is atioéster,with a sulfur atom replacing an oxygen atom of the usual carboxylic acid ester. This difference is important because thioesters are high-energy compounds. In other words, the hydrolysis of thioesters releases enough energy to drive other reactions. The transfer of the acetyl group to CoA is preceded by an oxidation reaction. The whole process involves several enzymes, all part of the pyruvate dehydrogenase complex. the overall reaction

Pyruvat + CoA-SH + NAD⁺-> Acetyl-CoA + CO₂+H⁺+NADH

isergonic (∆G°' = –33.4 kJ mol^–1= –8,0 kcal mol^–1) and NADH can be used to generate ATP via the electron transport chain.

How many enzymes are needed to convert pyruvate to acetyl-CoA?

Five enzymes make up the pyruvate dehydrogenase complex in mammals. they arePyruvatdehydrogenase (PDH), Dihydrolipoyltransacetylase, Dihydrolipoyldehydrogenase, Pyruvatdehydrogenasekinase,miPyruvat-Dehydrogenase-Phosphatase.The first three are involved in the conversion of pyruvate to acetyl-CoA. Kinase and phosphatase are enzymes used to control PDH and are present in a single polypeptide. The reaction takes place in five steps. Two enzymes catalyze reactionslipoic acid,a compound having one disulfide group in its oxidized form and two sulfhydryl groups in its reduced form.

Lipoic acid differs from other coenzymes in one respect. It is a vitamin and not a metabolite of a vitamin like many other coenzymes (Table 7.3). (The classification of lipoic acid as a vitamin is questionable. There is no evidence that it is required in human nutrition, but it is required for the growth of some bacteria and protists.) Lipoic acid can act as an oxidizing agent; The reaction involves the transfer of hydrogen that often accompanies biological oxidation-reduction reactions. Another reaction of lipoic acid is the formation of a thioester bond with the acetyl group before it is transferred to acetyl-CoA. Lipoic acid can act simply as an oxidizing agent, or it can participate in two reactions simultaneously: a redox reaction and the displacement of an acetyl group through transesterification.

The first step in the reaction sequence, which converts pyruvate to carbon dioxide and acetyl-CoA, is catalyzed by pyruvate dehydrogenase, as shown in Figure 19.4. This enzyme requires thiamine pyrophosphate (TPP; a metabolite of vitamin B₁or thiamine) as a coenzyme. The coenzyme is not covalently bound to the enzyme; They are held together by non-covalent interactions. milligram²⁺is also necessary. We saw the action of TPP as a coenzyme in the conversion of pyruvate to acetaldehyde catalyzed by pyruvate decarboxylase. In the pyruvate dehydrogenase reaction, an α-keto acid, pyruvate, loses carbon dioxide; the remaining two-carbon unit is covalently bound to TPP.

The second step of the reaction is catalyzed by dihydrolipoyl transacetylase. This enzyme requires lipoic acid as a coenzyme. Lipoic acid is covalently linked to the enzyme via an amide bond to the e-amino group of a lysine side chain. The two-carbon parent unit of pyruvate is transferred from thiamine pyrophosphate to lipoic acid, and in the process a hydroxyl group is oxidized to generate an acetyl group. The disulfide group of lipoic acid is the oxidizing agent, which in turn is reduced and the reaction product is a thioester. In other words, the acetyl group is now covalently linked to lipoic acid through a thioester bond (see Fig. 19.4).

The third step of the reaction is also catalyzed by dihydrolipoyltransacetylase. A CoA-SH molecule attacks the thioester bond and transfers the acetyl group to it. The acetyl group remains linked in a thioester bond; this time it appears as acetyl-CoA rather than esterified to lipoic acid. The reduced form of lipoic acid remains covalently bound to the dihydrolipoyl transacetylase (see Fig. 19.4). The reaction of pyruvate and CoA-SH has already reached the stage of the products carbon dioxide and acetyl-CoA, but the lipoic acid coenzyme is in a reduced form. The remaining steps regenerate lipoic acid, allowing transacetylase to catalyze other reactions.

In the fourth step of the overall reaction, the enzyme dihydrolipoyl dehydrogenase oxidizes the reduced lipoic acid from the sulfhydryl form to the disulfide form. Lipoic acid remains covalently bound to the transacetylase enzyme. to the enzyme through non-covalent interactions. This reduces FAD to FADH₂. FADH₂it is in turn reoxidized. The oxidizing agent is NAD.⁺, and NADH is the product along with reoxidized FAD. Enzymes like pyruvate dehydrogenase are called flavoproteins because of their attached FADs.

NAD Reduction⁺a NADH accompanies the oxidation of pyruvate to the acetyl group, and the general equation shows that two-electron transfer from pyruvate to NAD has occurred⁺(Equation 19.1). The electrons gained by NAD⁺in the production of NADH they are passed on to the electron transport chain in this step (the next step in aerobic metabolism). We will see that the transfer of electrons from NADH to oxygen will result in 2.5 ATP. Two pyruvate molecules are produced for every glucose molecule, so ultimately five ATP are made from each glucose in this step alone.

The reaction of pyruvate to acetyl-CoA is complex and requires three enzymes in addition to NAD, each with its own coenzyme.⁺Even the spatial orientation of individual enzyme molecules to one another is complex. In the case of the isolated enzymeE coli,the arrangement is quite compact, so that the different reaction steps can be perfectly coordinated. There is a core of 24-dihydrolipoyl transacetylase molecules. The 24 polypeptide chains are arranged in eight trimers, with each trimer occupying the top of a cube. It is 12 o'clockAbsPyruvate dehydrogenase dimers and occupy the edges of the cube. Finally, there are six dihydrolipoyl dehydrogenase dimers on the six sides of the cube (Figure 19.5). Note that many levels of structure combine to create a suitable environment for the conversion of pyruvate to acetyl-CoA. Each enzyme molecule in thisThe matrix has its own tertiary structure, and the matrix itself has the cubic structure that we just saw.

A compact assembly, such as the pyruvate dehydrogenase multi-enzyme complex, has two main advantages over an assembly in which the various components are more widely distributed. First, because the reagents and enzymes are in close proximity to each other, the various stages of the reaction can proceed more efficiently. The role of lipoic acid is particularly important here. Remember that lipoic acid is covalently linked to the enzyme transacetylase, which occupies a central position in the complex. Lipoic acid and the lysine chain to which it is attached are long enough to act as a "rocker" that can be moved into place at any of the reaction steps (Figure 19.4). Under arm action, lipoic acid can move to the pyruvate dehydrogenase site to pick up the two-carbon moiety and then transfer it to the transacetylase active site. The acetyl group can then be transesterified from lipoic acid to CoA-SH. Finally, lipoic acid can oscillate to the active site of the dehydrogenase so that the sulfhydryl groups can be reoxidized to a disulfide.

A second benefit of a multi-enzyme complex is that regulatory controls can be applied more efficiently in such a system than in a single enzyme molecule. In the case of the pyruvate dehydrogenase complex, the control factors are closely related to the multienzyme complex itself.

Summary

The two-carbon unit required at the beginning of the citric acid cycle is obtained by converting pyruvate to acetyl-CoA.

This conversion requires the three main enzymes of the pyruvate dehydrogenase complex and the cofactors TPP, FAD, NAD⁺and lipoic acid.

The general reaction of pyruvate dehydrogenase is the conversion of pyruvate, NAD⁺, y CoA-SH for acetyl-CoA, NADH + H⁺, and society_2.

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Biochemistry: The Citric Acid Cycle: How Pyruvate is Converted to Acetyl-CoA |