Different mechanisms of “lactylgenesis”. Two forms of Kla have been described, including K (L-la) and K (D-la). The K (L-la) proposed by Zhang et al. described an enzymatic mechanism, where l-lactate was first transformed into its activated form, L-lactyl-CoA. L-lactyl-CoA then acts as a direct substrate for K (L-la), transferring lactyl groups to lysine residues on histones as the aid of “writers”, including p300 and CBP. The K (D-la) presents a non-enzymatic process from MGO, LGSH to lactoyllysine as described by Gaffney et al. The K (D-la) would presumably accumulate in the absence of a dedicated “eraser” protein, meaning that it could be tightly regulated by the “erasers”, such as HDAC1, 2, 3, 8 and SIRT2, 3.
Liu X, Zhang Y, Li W, Zhou X. Lactylation, an emerging hallmark of metabolic reprogramming: Current progress and open challenges. Front Cell Dev Biol. 2022 26;10:972020.