Parapyruvate, an Impurity in Pyruvate Supplements, Induces Senescence in Human Fibroblastic Hs68 Cells via Inhibition of the α-Ketoglutarate Dehydrogenase Complex.

Abstract

Commercial dietary supplements of calcium pyruvate claim to be beneficial for losing weight, increasing muscle endurance, and regulating metabolism. Most industrial preparations have some impurities, including parapyruvate. Parapyruvate is an inhibitor of the α-ketoglutarate dehydrogenase complex (KGDHC). However, the effect and mechanism of parapyruvate on cell senescence and the content of parapyruvate in the dietary supplements of calcium pyruvate are unknown. In this study, we prepared pure parapyruvate with a purity of 99.8 ± 0.1% and investigated its ability to inhibit KGDHC activity and affect fibroblast senescence. Parapyruvate dose-dependently decreased KGDHC activity, with an IC50 of 4.13 mM and induced Hs68 cell senescence. Calcium ions, a KGDHC activator, antagonized the senescent effects of parapyruvate. The parapyruvate content was 1.4 ± 0.1% to 10.6 ± 0.2% in five brands of calcium pyruvate supplements. In this study, we showed that parapyruvate strongly induces Hs68 cell senescence by inhibiting KGDHC activity. Because of its KGDHC inhibition activity, the parapyruvate content should be an important issue for the food safety of calcium pyruvate supplements.