PyruvatdehydrogenaseKomplexStörung

Pyruvatdehydrogenase, often abbreviated as PDH, is a crucial enzyme complex found in the mitochondria of eukaryotic cells. Its primary function is to catalyze the irreversible conversion of pyruvate to acetyl-CoA. This reaction is a critical link between glycolysis, the breakdown of glucose, and the citric acid cycle, a central pathway for energy production.

The pyruvate dehydrogenase complex is a multi-enzyme system composed of three distinct enzymes: pyruvate dehydrogenase (E1), dihydrolipoyl transacetylase (E2), and dihydrolipoyl dehydrogenase (E3). These enzymes work in a coordinated fashion, with the product of one reaction serving as the substrate for the next. The reaction also requires five cofactors: thiamine pyrophosphate (TPP), lipoamide, coenzyme A (CoA), flavin adenine dinucleotide (FAD), and nicotinamide adenine dinucleotide (NAD+).

The regulation of PDH activity is tightly controlled to ensure that energy production meets cellular demands. It is regulated both by product inhibition and covalent modification. High levels of acetyl-CoA and NADH inhibit the complex, signaling that sufficient energy is available. Conversely, low levels of these products, along with the presence of pyruvate, activate the complex. PDH kinase and PDH phosphatase enzymes control the phosphorylation state of E1, which in turn determines the activity of the entire complex.

Defects in the PDH complex can lead to a range of severe neurological disorders collectively known as pyruvate dehydrogenase deficiency. These conditions result in the accumulation of pyruvate and lactic acid, leading to impaired brain function.