pyruvate dehydrogenase complex

Definition

Target type: cellularcomponent

A multi-enzyme complex that catalyzes the oxidative decarboxylation of pyruvate to form acetyl-CoA. The complex comprises multiple copies of three enzymes referred to as E1, E2 and E3: pyruvate dehydrogenase (E1, which may be a homodimer or a heterotetramer of two alpha and two beta subunits, depending on species), dihydrolipoamide S-acetyltransferase (E2), and dihydrolipoamide dehydrogenase (E3). Additional proteins may also be present. [PMID:36863425]

The pyruvate dehydrogenase complex (PDC) is a multi-enzyme complex that catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA, a key step in cellular respiration. The complex is located in the mitochondrial matrix of eukaryotic cells and is composed of three major enzyme components: pyruvate dehydrogenase (E1), dihydrolipoyl transacetylase (E2), and dihydrolipoyl dehydrogenase (E3).

E1 is a tetrameric enzyme that catalyzes the decarboxylation of pyruvate and the formation of a hydroxyethyl derivative bound to thiamine pyrophosphate (TPP) in the active site. This hydroxyethyl group is then transferred to the lipoyl moiety of E2.

E2 is a dimeric enzyme with multiple copies of lipoyl domains. The lipoyl moiety is a flexible arm that can swing between the active sites of E1, E2, and E3. The lipoyl group is responsible for carrying the acetyl group from E1 to E2 and the reduced lipoyl group from E2 to E3.

E3 is a dimeric enzyme that oxidizes the reduced lipoyl group of E2 using NAD+ as the electron acceptor. The reduced form of E3 is then reoxidized by electron transfer to FAD, which is then reoxidized by NAD+.

The PDC complex is highly regulated by a variety of mechanisms, including phosphorylation, product inhibition, and allosteric regulation. The complex is also tightly controlled by the availability of its substrates, pyruvate, NAD+, and CoA.

In addition to the three major enzyme components, the PDC complex contains several regulatory proteins, including pyruvate dehydrogenase kinase and pyruvate dehydrogenase phosphatase. These proteins regulate the activity of the complex by phosphorylating and dephosphorylating E1, respectively. Phosphorylation of E1 inactivates the enzyme, while dephosphorylation activates it.

The cellular component of the pyruvate dehydrogenase complex is the mitochondrial matrix. This is the space within the inner membrane of mitochondria where the complex is located. The matrix contains a high concentration of enzymes and other molecules involved in cellular respiration, including the citric acid cycle and oxidative phosphorylation.

The mitochondrial matrix provides the appropriate environment for the PDC complex to function optimally. This includes the presence of substrates, such as pyruvate, NAD+, and CoA, as well as the absence of inhibitory molecules. The matrix also provides a suitable pH and temperature for the complex to operate efficiently.

The PDC complex is an essential component of cellular respiration, playing a critical role in the production of ATP. It is tightly regulated and integrated into the cellular metabolism, ensuring that the complex operates effectively to meet the energy needs of the cell.'
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Proteins (2)

Compounds (12)