pyruvate dehydrogenase (NAD+) activity

Definition

Target type: molecularfunction

Catalysis of the reaction: pyruvate + CoA + NAD+ = acetyl-CoA + CO2 + NADH. [GOC:mah, ISBN:0201090910]

Pyruvate dehydrogenase (NAD+) activity is a key enzyme in cellular metabolism, specifically in the transition between glycolysis and the citric acid cycle. It catalyzes the irreversible oxidative decarboxylation of pyruvate, converting it into acetyl-CoA. This reaction is essential for the production of energy in the form of ATP via aerobic respiration.

The enzyme complex consists of three distinct subunits: pyruvate dehydrogenase (E1), dihydrolipoyl transacetylase (E2), and dihydrolipoyl dehydrogenase (E3). Each subunit plays a critical role in the overall catalytic process:

1. **E1** (pyruvate dehydrogenase): This subunit is responsible for the initial decarboxylation of pyruvate, yielding carbon dioxide and a hydroxyethyl derivative.
2. **E2** (dihydrolipoyl transacetylase): This subunit transfers the hydroxyethyl group from E1 to lipoic acid, a cofactor bound to E2. The lipoyl-dihydroxyethyl group is then oxidized, resulting in the formation of acetyl-CoA.
3. **E3** (dihydrolipoyl dehydrogenase): This subunit catalyzes the reoxidation of the reduced lipoic acid, using NAD+ as an electron acceptor. The reduced form of NAD+ (NADH) is then used in the electron transport chain to generate ATP.

The activity of pyruvate dehydrogenase is tightly regulated by a complex interplay of factors, including:

* **Substrate availability:** The enzyme is active when pyruvate is available in sufficient quantities.
* **Product accumulation:** High levels of acetyl-CoA and NADH can inhibit the enzyme's activity, preventing excessive flux through the citric acid cycle.
* **Phosphorylation/dephosphorylation:** The enzyme can be reversibly phosphorylated by pyruvate dehydrogenase kinase, leading to its inactivation. Dephosphorylation by pyruvate dehydrogenase phosphatase reactivates the enzyme.

In summary, pyruvate dehydrogenase (NAD+) activity plays a crucial role in the energy metabolism of cells by linking glycolysis to the citric acid cycle and ultimately ATP production. Its regulation ensures that the enzyme operates efficiently and avoids excessive flux through the metabolic pathway.'
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Proteins (1)

Compounds (1)