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  • Ketone Body Acetoacetate Buffers Methylglyoxal via a Non-enzymatic Conversion during Diabetic and Dietary Ketosis.

Ketone Body Acetoacetate Buffers Methylglyoxal via a Non-enzymatic Conversion during Diabetic and Dietary Ketosis.

Cell chemical biology (2017-08-19)
Trine Salomón, Christian Sibbersen, Jakob Hansen, Dieter Britz, Mads Vandsted Svart, Thomas Schmidt Voss, Niels Møller, Niels Gregersen, Karl Anker Jørgensen, Johan Palmfeldt, Thomas Bjørnskov Poulsen, Mogens Johannsen
ABSTRACT

The α-oxoaldehyde methylglyoxal is a ubiquitous and highly reactive metabolite known to be involved in aging- and diabetes-related diseases. If not detoxified by the endogenous glyoxalase system, it exerts its detrimental effects primarily by reacting with biopolymers such as DNA and proteins. We now demonstrate that during ketosis, another metabolic route is operative via direct non-enzymatic aldol reaction between methylglyoxal and the ketone body acetoacetate, leading to 3-hydroxyhexane-2,5-dione. This novel metabolite is present at a concentration of 10%-20% of the methylglyoxal level in the blood of insulin-starved patients. By employing a metabolite-alkyne-tagging strategy it is clarified that 3-hydroxyhexane-2,5-dione is further metabolized to non-glycating species in human blood. The discovery represents a new direction within non-enzymatic metabolism and within the use of alkyne-tagging for metabolism studies and it revitalizes acetoacetate as a competent endogenous carbon nucleophile.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Pepsin from porcine gastric mucosa, lyophilized powder, ≥3,200 units/mg protein
Sigma-Aldrich
Albumin from human serum, lyophilized powder, Fatty acid free, Globulin free, ≥99% (agarose gel electrophoresis)
Sigma-Aldrich
Tris(3-hydroxypropyltriazolylmethyl)amine, 95%
Sigma-Aldrich
γ-Globulins from human blood, ≥99% (electrophoresis)
Sigma-Aldrich
Aminoguanidine bicarbonate, 97%
Sigma-Aldrich
Methylglyoxal 1,1-dimethyl acetal, ≥97%