Fig. 1: Lactate synthesis and regulatory mechanisms of lactylation.
From: The role of protein lactylation in brain health and disease: current advances and future directions
The lactate metabolism pathway and the regulatory mechanisms of lactylation are illustrated as shown. Lactylation modification targets include both histones and non-histones, and it is accomplished through two pathways: enzyme-catalyzed and non-enzyme-catalyzed reactions. The first pathway: l-lactate which is transported into the cell through MCT or synthesized from pyruvate is the primary substrate for enzyme-catalyzed lactylation. The catalytic process of lactylation by the writer requires the synthesis of lactyl-CoA, while AARS1 uses lactyl-AMP as an intermediate. The balance of lactylation modification is ultimately regulated by erasers and readers, with the former removing lactylation marks and the latter influencing the addition of lactyl groups. The second pathway: non-enzyme-catalyzed lactylation refers to the spontaneous interaction between lactoylglutathione and lysine residues, mainly regulated by GLO1 and GLO2. The substrate, lactoylglutathione, is derived from a specific metabolic pathway from glycolysis.
