Fig. 4: Potential lactyltransferase and delactylase.
From: Protein lactylation in cancer: mechanisms and potential therapeutic implications
ACSS2 and GTPSCS activate l-lactate into l-lactyl-CoA, which is subsequently catalyzed by HATs, including p300/CBP, GCN5, HBO1, MOF and TIP60, to install l-lactylation. In addition, l-lactate can be directly activated by AARS to lactate-AMP and then transferred to target proteins for l-lactylation. In contrast to l-lactylation, d-lactylation can be caused by NECMs from metabolites in the GLO pathway, which branches off from G3P in glycolysis. The class I and III (sirtuins) HDAC families are reported as potential delactylases, although further investigations are needed. Enzymes that install and remove lactylation are outlined in red and blue, respectively. SIRT, silent information regulator.
