betahydroxybutyrylation

Betahydroxybutyrylation, usually referred to as beta-hydroxybutyrylation (Kbhb), is a post-translational modification in which a beta-hydroxybutyryl group is covalently attached to lysine residues on proteins, most prominently on histone tails. The modification is derived from the ketone body beta-hydroxybutyrate (BHB), linking cellular energy status to chromatin regulation.

Biological context and distribution indicate that beta-hydroxybutyrylation is dynamically regulated by metabolic state. It has been detected on histones, especially H3 and H4, and is enriched at promoters and regulatory regions of actively transcribed genes. Levels of Kbhb increase in conditions that elevate BHB, such as fasting or ketogenic diets, suggesting a role in metabolic gene programs and energy homeostasis. While histones are the primary substrates studied, non-histone proteins may also bear bhb modifications, extending its potential regulatory scope.

Enzymology behind the modification involves writer enzymes that transfer the bhb group from beta-hydrobutyric acid donors to lysine residues. The p300/CBP family of histone acetyltransferases has been implicated as capable of catalyzing bhb transfer in the presence of BHB. Removal of bhb marks is achieved by deacylases, including histone deacetylases and sirtuins, indicating reversibility and potential dynamic regulation analogous to other lysine acylations.

Detection and research surrounding beta-hydroxybutyrylation are ongoing. It is identified by mass spectrometry and, in many studies, by antibodies specific to the bhb modification. Ongoing work seeks to clarify its precise functional roles, the full spectrum of substrates, and its significance in physiology and disease.