Pyruvate dehydrogenase E1 component subunit beta, mitochondrial

PDHB (pyruvate dehydrogenase E1 component subunit beta, mitochondrial) is a catalytic subunit of the pyruvate dehydrogenase (PDH) complex, a key mitochondrial enzyme that links glycolysis to the tricarboxylic acid cycle. Together with PDHA1, it forms the E1 subunit and catalyzes the thiamine pyrophosphate-dependent decarboxylation of pyruvate to acetyl-CoA (UniProt: P11177). This enzyme is essential for cellular energy metabolism, particularly in tissues with high metabolic demand such as the brain.

Mutations in PDHB cause pyruvate dehydrogenase E1-beta deficiency (PDHBD, MIM 614111), a rare enzymatic disorder characterized by primary lactic acidosis and ranging from severe neonatal presentations to chronic neurologic dysfunction with central nervous system abnormalities (UniProt: P11177). The PDH complex is critical for neuronal function, making it relevant to neurodegenerative conditions.

PDHB is downregulated in Alzheimer's disease brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.40 across subcellular fractions in post-mortem samples analyzed by mass spectrometry (Chaparral AD proteomics). This reduction may reflect compromised mitochondrial energy metabolism and the glycolytic-to-TCA coupling that is increasingly implicated in AD pathogenesis.