Phosphorylation of T107 by CamKIIδ Regulates the Detoxification Efficiency and Proteomic Integrity of Glyoxalase 1

The glyoxalase system is a highly conserved and ubiquitously expressed enzyme system, which is responsible for the detoxification of methylglyoxal (MG), a spontaneous by-product of energy metabolism. This study is able to show that a phosphorylation of threonine-107 (T107) in the (rate-limiting) Glyoxalase 1 (Glo1) protein, mediated by Ca2+/calmodulin-dependent kinase II delta (CamKII delta), is associated with elevated catalytic efficiency of Glo1 (lower K-M; higher V(ma)x). Additionally, we observe proteasomal degradation of non-phosphorylated Glo1 via ubiquitination does occur more rapidly as compared with native Glo1. The absence of CamKII delta is associated with poor detoxification capacity and decreased protein content of Glo1 in a murine CamKII delta knockout model. Therefore, phosphorylation of T107 in the Glo1 protein by CamKII delta is a quick and precise mechanism regulating Glo1 activity, which is experimentally linked to an altered Glo1 status in cancer, diabetes, and during aging.