Lysine β-hydroxybutyrylation: A metabolic-epigenetic interface in health and disease.
Level 5 - mechanism / opinion, no new human data
Narrative review of biochemical mechanisms and preclinical studies without human clinical trials
PubMed 42284641 · doi:10.1016/j.phymed.2026.158410
What was done
This narrative review summarizes literature regarding lysine β-hydroxybutyrylation (Kbhb), detailing the generation of β-hydroxybutyryl-CoA, molecular machinery (writers, erasers, readers), crosstalk with other lysine acylations, and implicated roles in fasting, immune memory, cancer, and neuroprotection.
What was found
No quantitative findings or empirical metrics are reported in the abstract. Qualitatively, the review identifies p300/CBP as a Kbhb writer, HDACs and sirtuins as erasers, and ENL as an H3K9bhb reader, while noting that shared enzymatic machinery and pleiotropic β-hydroxybutyrate signaling obscure direct causal attribution.
Why it matters
The paper clarifies that Kbhb is a context-dependent acylation rather than uniformly protective or deleterious, emphasizing the analytical rigor required to separate epigenetic Kbhb actions from general ketone-body signaling.
Limits
The abstract describes a narrative review with no original experimental data, quantitative synthesis, or human clinical trial results. Functional attribution in the field is limited by overlapping enzymatic machinery across different acylation pathways.
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