The pyruvate dehydrogenase complex (PDHc) is a crucial metabolic enzyme complex found in all aerobic organisms. It catalyzes the conversion of pyruvate, the product of glycolysis, into acetyl-CoA, a key substrate for the citric acid cycle and fatty acid synthesis. This multienzyme complex uses multiple cosubstrates and tethered reaction intermediates to efficiently channel substrates through its catalytic steps. With a total size of 5-12 MDa, PDHc is among the largest biomolecular assemblies. It consists of three enzymatic components acting sequentially: E1 (pyruvate dehydrogenase), E2 (dihydrolipoamide acetyltransferase), and E3 (dihydrolipoamide dehydrogenase). In eukaryotes, an additional E3-binding protein (E3BP) recruits E3 to the complex. E2 (and E3BP) subunits form the structural core, typically exhibiting octahedral or icosahedral symmetry, while E1 and E3 bind to the core as peripheral subunits. Advances in structural biology, particularly cryo-EM, X-ray crystallography, and nuclear magnetic resonance (NMR), have provided valuable insights into PDHc organization, assembly principles, and species-specific variation. Here, we review diverse PDHc architectures across phylogenetic groups. Understanding these structural and functional adaptations is essential for fully deciphering PDHc regulation and its role in metabolism.
Meinhold et al. (Wed,) studied this question.