Moreover, Ser189 O-GlcNAc could act as a “molecular glue” to stabilize the substrate binding pocket on the MDH1 monomer, improve substrate binding and stability, and ultimately promote the enzymatic activity of MDH1.129 Further determination of the mechanism by which protein glycosylation modifies metabolic reprogramming will open up novel insights for therapeutic intervention in metabolic diseases and tumors. This evidence concerns the gene MDH1 and metabolic disease.