The Glyoxalase System and Methylglyoxal-Derived Carbonyl Stress in Sepsis: Glycotoxic Aspects of Sepsis Pathophysiology

• Published in: International journal of molecular sciences Vol. 18; no. 3; p. 657
• Main Authors: Schmoch, Thomas, Uhle, Florian, Siegler, Benedikt H, Fleming, Thomas, Morgenstern, Jakob, Nawroth, Peter P, Weigand, Markus A, Brenner, Thorsten
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.03.2017; MDPI
• Subjects: Animals; Carbonyls; Glucose; glyoxalase; Humans; Hyperglycemia; Immune system; immunometabolism; Insulin; Insulin resistance; Intensive care units; Lactoylglutathione Lyase - metabolism; Leukocytes (mononuclear); metabolic stress; Metabolites; methylglyoxal; Mortality; Nitric oxide; Organs; Peripheral blood mononuclear cells; Protein Carbonylation; Pyruvaldehyde; Pyruvaldehyde - metabolism; Pyruvaldehyde - toxicity; reactive carbonyl species; Review; Sepsis; Sepsis - etiology; Sepsis - metabolism; Septic shock; Septicemia; Stress, Physiological; Superoxide; Tumor necrosis factor-TNF; Warburg effect; Germany; methylglyoxal; septic shock; immunometabolism; glyoxalase; metabolic stress; reactive carbonyl species; sepsis; Warburg effect
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms18030657

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.