title: The Glyoxalase System and Methylglyoxal-Derived Carbonyl Stress in Sepsis: Glycotoxic Aspects of Sepsis Pathophysiology.
abstract: Sepsis remains one of the leading causes of death in intensive care units. Although sepsis is caused by a viral, fungal or bacterial infection, it is the dysregulated generalized host response that ultimately leads to severe dysfunction of multiple organs and death. The concomitant profound metabolic changes are characterized by hyperglycemia, insulin resistance, and profound transformations of the intracellular energy supply in both peripheral and immune cells. A further hallmark of the early phases of sepsis is a massive formation of reactive oxygen (ROS; e.g., superoxide) as well as nitrogen (RNS; e.g., nitric oxide) species. Reactive carbonyl species (RCS) form a third crucial group of highly reactive metabolites, which until today have been not the focus of interest in sepsis. However, we previously showed in a prospective observational clinical trial that patients suffering from septic shock are characterized by significant methylglyoxal (MG)-derived carbonyl stress, with the glyoxalase system being downregulated in peripheral blood mononuclear cells. In this review, we give a detailed insight into the current state of research regarding the metabolic changes that entail an increased MG-production in septicemia. Thus, we point out the special role of the glyoxalase system in the context of sepsis.
authors.affiliation: Department of Anesthesiology, Heidelberg University Hospital, 69120 Heidelberg, Germany. Thomas.Schmoch@med.uni-heidelberg.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmoch
authors.affiliation: Department of Anesthesiology, Heidelberg University Hospital, 69120 Heidelberg, Germany. Florian.Uhle@med.uni-heidelberg.de.
authors.forename: Florian
authors.initials: F
authors.lastname: Uhle
authors.affiliation: Department of Anesthesiology, Heidelberg University Hospital, 69120 Heidelberg, Germany. Benedikt.Siegler@med.uni-heidelberg.de.
authors.forename: Benedikt H
authors.initials: BH
authors.lastname: Siegler
authors.affiliation: Department of Medicine I and Clinical Chemistry, Heidelberg University Hospital, 69120 Heidelberg, Germany. Markus.Weigand@med.uni-heidelberg.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fleming
authors.affiliation: Department of Medicine I and Clinical Chemistry, Heidelberg University Hospital, 69120 Heidelberg, Germany. Thomas.Fleming@med.uni-heidelberg.de.
authors.forename: Jakob
authors.initials: J
authors.lastname: Morgenstern
authors.affiliation: Department of Medicine I and Clinical Chemistry, Heidelberg University Hospital, 69120 Heidelberg, Germany. Jakob.Morgenstern@med.uni-heidelberg.de.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Nawroth
authors.affiliation: Department of Anesthesiology, Heidelberg University Hospital, 69120 Heidelberg, Germany. Peter.Nawroth@med.uni-heidelberg.de.
authors.forename: Markus A
authors.initials: MA
authors.lastname: Weigand
authors.affiliation: Department of Anesthesiology, Heidelberg University Hospital, 69120 Heidelberg, Germany. Thorsten.Brenner@med.uni-heidelberg.de.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Brenner
mesh_terms: D000818:Animals; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000378:metabolism*; D050050:Protein Carbonylation; D011765:Pyruvaldehyde / Q000378:metabolism* / Q000633:toxicity; D018805:Sepsis / Q000209:etiology / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D011765:Pyruvaldehyde; D007791:Lactoylglutathione Lyase
keywords: Warburg effect; glyoxalase; immunometabolism; metabolic stress; methylglyoxal; reactive carbonyl species; sepsis; septic shock