Acetylation regulates the substrate accessibility to metabolic enzymes. (A) Acetylation can regulate the substrate accessibility to metabolic enzymes by modifying the conserved lysine residues located on the hydrophilic surface of SDHA to hinder the entry of substrate (S) into the active site. (B) Acetylation can also alter the access of cytoplasmic substrates to GAPDH by promoting nuclear accumulation of GAPDH. Enzymes, acetylated lysine residues (K), and active sites are labeled as in Fig. 1. N, nucleus; C, cytoplasm.