Ketogenesis impact on liver metabolism revealed by proteomics of lysine β-hydroxybutyrylation.

ABSTRACT: Ketone bodies are bioactive metabolites that function as energy substrates, signaling molecules, and regulators of histone modifications. β-hydroxybutyrate (β-OHB) is utilized in lysine β-hydroxybutyrylation (Kbhb) of histones, and associates with starvation-responsive genes, effectively coupling ketogenic metabolism with gene expression. The emerging diversity of the lysine acylation landscape prompted us to investigate the full proteomic impact of Kbhb. Global protein Kbhb is induced in a tissue-specific manner by a variety of interventions that evoke β-OHB. Mass spectrometry analysis of the β-hydroxybutyrylome in mouse liver revealed 891 sites of Kbhb within 267 proteins enriched for fatty acid, amino acid, detoxification, and one-carbon metabolic pathways. Kbhb inhibits S-adenosyl-L-ho

SUBMITTER: Koronowski KB 

PROVIDER: S-EPMC8372761 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature