The activity of glyoxylase 1 is regulated by glucose-responsive phosphorylation on Tyr136

• DOI: 10.1016/j.molmet.2021.101406
• Publication Date: 2021-11-25T01:56:19Z
• Authors: Fabiola Garcia Co...; Daniel Pfaff; Angela Wirth; Andrea Schlotterer; Rebekka Medert; Jakob Morgenstern; Tobias Weber; Hans-Peter Hammes; Thomas Fleming; Peter Paul Nawroth; Marc Freichel; Aurelio A. Teleman
• Keywords: Carbohydrate Metabolism

Methylglyoxal (MG) is a highly reactive α-oxoaldehyde that glycates proteins. MG has been linked to the development of diabetic complications: major precursor advanced glycation end products (AGEs), risk marker for complications in humans. Furthermore, flies and fish with elevated develop insulin resistance, obesity, hyperglycemia. detoxified large part through glyoxalase system, whose rate-limiting enzyme I (Glo1). Hence, we aimed study how Glo1 activity regulated. We studied regulation effect post-translational modifications tissue culture mouse models diabetes. show promoted by phosphorylation on Tyrosine 136 via multiple kinases. find Y136 responds bimodal fashion glucose levels, increasing cell from 0 mM 5 (physiological) glucose, then decreasing at higher concentrations, both These data, together published findings leads hyperglycemia, suggest existence deleterious positive feedback loop whereby hyperglycemia reduced activity, contributing which turn promote perturbations elevating either or have potential start an auto-amplifying complications.