Fig. 5: Previously undescribed metabolite malonyl-lysine connects lysine metabolism to reduced fatty acid synthesis.

A Structure and potential formation of Malonyl-lysine, a previously undescribed metabolite and potentially relationship to fatty acid synthesis. B Non-enzymatic formation of Nε-Malonyl-lysine by incubation of lysine and Malonyl-CoA. Both ¹³C₆ and ¹²C₆ lysine were used in the reaction, and detected by targeted metabolomics assay with heavy and light transitions. C Accelerated formation of Nε-malonyl-lysine in hypertension. Animals from Fig. 3D were analyzed for the formation of Nε-malonyl-lysine (n = 3 independent animals). D Nε-malonyl-lysine abundance in kidney cortices of hypertensive animals with and without lysine treatment (n = 4 independent animals for control, 8% 2w, and 8% 3w diet, and n = 5 for 4% diet, p < 0.05 in a two-tailed t-test). E Nε-malonyl-CoA abundance in kidney cortices of hypertensive animals with and without lysine treatment. Each dot is an observation from an independent animal, error bar = SEM. F Nε-acetyl-lysine abundance in kidney cortices (n = 5 independent animals, p < 0.05 in a two-tailed t-test). G Acetyl-CoA abundance in kidney cortices. Each dot is an observation from an independent animal, error bar = SEM. H Immunoblot analysis of protein acetylation and malonylation in cortex lysates as detected with respective antibodies. β-Actin serves as loading control. Representative run of in total n = 2 runs for n = 4 independent animals per group. Source data for this figure is available.