Research Project Summary

Across all domains of life, the pyruvate dehydrogenase (PDH) complex is essential to aerobic energy metabolism. Both prokaryotic and eukaryotic cells contain the PDH complex. This complex is composed of the E1, E2, and E3 subunits; these enzymes convert pyruvate into Acetyl-CoA through pyruvate decarboxylation. The E1 subunit catalyzes the reaction and involves decarboxylation of the pyruvate at the thiamine pyrophosphate cofactor, forming a hydroxyethyl-TPP intermediate. The E2 subunit then transfers the acetyl group to coenzyme A, producing acetyl-CoA and leaving a reduced lipoamide. The remaining electrons on the lipoamide are transferred to E3, then ultimately to NAD+, restarting the process of aerobic energy metabolism. Different organisms exhibit different structures in their respective PDH. Gram-negative bacteria possess a core of 24 E2 subunits aligned in octahedral symmetry, while Gram-positive bacteria and eukaryotes contain 60 E2 subunits that are arranged in icosahedral symmetry. In eukaryotic cells, strict phosphorylation-dependent regulation of the E1 subunit prevents further carbon skeletons from entering the citric acid cycle. This process of phosphorylation has previously only been identified in eukaryotic cells. However, recent analysis has uncovered that the Gram-negative bacterium Caulobacter crescents contain, an E1 beta protein exhibiting properties previously only present in eukaryotic cells, such as a lipoyl domain. This uniqueness displayed in Caulobacter crescents is important in furthering our understanding of bacterial evolution and the specific processes that control metabolic activity.

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