What are the three enzymes included in the pyruvate dehydrogenase system

The pyruvate dehydrogenase system is mainly composed of three key enzymes: pyruvate dehydrogenase, dihydrolipoyl transacetylase, and dihydrolipoyl dehydrogenase. These three enzymes work together to complete the process of oxidative decarboxylation of pyruvate to produce acetyl CoA.

1. Pyruvate dehydrogenase:

Pyruvate dehydrogenase is the core component of the complex, responsible for catalyzing the decarboxylation reaction of pyruvate. This enzyme uses thiamine pyrophosphate as a coenzyme to remove the carboxyl group from the pyruvate molecule and generate the hydroxyethyl TPP intermediate. Its activity is regulated by multiple factors, including feedback inhibition of the products acetyl CoA and NADH, as well as regulation of hormones such as insulin.

2. Dihydrolipoyl transacetylase:

Dihydrolipoyl transacetylase contains a thioamide cofactor, which acts as a flexible "long arm" domain to transfer substrates between enzyme complexes. It oxidizes hydroxyethyl to acetyl and transfers acetyl to coenzyme A. This enzyme plays a crucial role in maintaining the structural integrity of the complex, and its active center contains thiol groups that are sensitive to oxidative stress.

3. Dihydrolipoyl dehydrogenase:

Dihydrolipoyl dehydrogenase, with FAD as a subunit, is responsible for the re oxidation of reduced lipoamide. This enzyme transfers electrons to NAD+to generate NADH, completing the redox cycle. Its activity deficiency can lead to metabolic disorders such as lactic acidosis, which can be seen clinically in patients with hereditary pyruvate dehydrogenase complex deficiency. These three enzymes, along with five cofactors TPP, lipoic acid, FAD, NAD+, and CoA, form a multifunctional enzyme complex. Adequate intake of B vitamins should be ensured in daily diet, especially thiamine vitamin B1 and riboflavin vitamin B2, which are precursors of related cofactors. Regular aerobic exercise can promote mitochondrial function and indirectly maintain enzyme activity. When there is an unexplained increase in lactate or neurological symptoms, it is recommended to evaluate enzyme function through specialized tests such as blood amino acid analysis and urine organic acid testing.