(A) Schematic summary of pyruvate-participated metabolic pathways. In addition to serving as electron acceptor, pyruvate may be used as a substrate in the synthesis of various metabolites, including acetyl-CoA, α-KG, succinate, OAA, alanine and aspartate. These metabolites can be used for the synthesis of proteins, lipids and nucleotides, thus supporting cell proliferation. (B) 1 mM alanine, (C) 0.5 mM ethyl-acetoacetate, (D) 1 mM dimethyl-α-KG, (E) 1 mM dimethyl-succinate, (F) 1 mM diethyl-OAA and (G) 1 mM aspartate were used to replace pyruvate to rescue 143B206 cells. Representative proliferation curves are shown. Error bars indicate SD of ≥ 5 replicates. **p < 0.01.