[Methylglyoxal--test for biological dysfunctions of homeostasis and endoecology, low cytosolic glucose level, and gluconeogenesis from fatty acids].

Abstract

If a lot of carbohydrates cannot be in vivo stored as glycogen, the synthesis of palmitic fatty acid (FA) from glucose and its adipocyte deposition as triglycerides are under way in phylogenesis. With impaired biological function of exotrophy (fasting, early postnatality, hibernation), the cells perform a reverse process--the synthesis of glucose from FA. Physiologically, the substrate of gluconeogenesis is acetyl-CoA that is converted by the malate --> 9 piruvate --> glucose pathway in the glyoxalate cycle. Under the pathological conditions of hypoxia and energy deficiency, gluconeogenesis occurs without ATP consumption via the methylglyoxalate pathway (MGP) while using as a substrate of ketone bodies: butyric acid (butyrate) --> beta-hydroxybutyrate --> acetoacetate --> acetone --> acetol --> methylglyoxal (MG) --> S-D-lactolglutathione --> D-lactate --> piruvate --> D-lactate. Under physiological conditions, this pathway of gluconeogenesis does not work. The authors hold that gene expression and gluconeogenesis occur via the MGP when glucose levels are low in the cell cytosol (glycopenia) and FA cannot be oxidized in the mitochondria. Cytosol, intercellular medium, plasma show elevated levels of MG and D-lactate, to which it converts under the action of glyoxalases I and II. Glycopenia develops in fasting, diabetes mellitus, metabolic syndrome, renal failure, phenofibrate therapy, impaired function of exotrophy--excessive dietary intake of saturated and trans fatty acids. The chemical interaction of MG with amino acid residues of lysine and arginine leads to protein denaturation during carbonylation--glycosylation and impaired biological function of endoecology. The determination of plasma MG and D-lactate may be a test for glycopenia, compensatory activation of gluconeogenesis from FA or for the evaluation of endogenous intoxication.