赖氨酸β-羟丁酰化：健康与疾病中的代谢-表观遗传界面
Lysine β-hydroxybutyrylation: A metabolic-epigenetic interface in health and disease.
摘要(中文译文)
赖氨酸β-羟基丁酰化（Kbhb）是一种由β-羟基丁酸衍生的赖氨酸酰化修饰，将酮体代谢与染色质调控及非组蛋白蛋白功能联系起来。Kbhb最初被描述为一种禁食响应性组蛋白标记，如今已被认为与免疫记忆、代谢适应、癌症代谢和神经保护相关。本综述将Kbhb重新定义为一种情境依赖性的代谢酰化系统。我们讨论了β-羟基丁酰辅酶A的代谢来源、Kbhb的写入、读取和擦除机制、其与乙酰化、乳酸化和巴豆酰化的交互作用，以及区分Kbhb驱动机制与更广泛β-羟基丁酸生物学所需的证据标准。近期研究已确定p300/CBP为Kbhb写入酶，HDACs和sirtuins为擦除酶，ENL为H3K9bhb读取蛋白。Kbhb还与CD8 T细胞记忆、禁食响应性染色质重塑、肿瘤代谢重编程及非组蛋白蛋白调控相关。然而，共享的酶、重叠的酰化程序及多效性BHB信号传导使因果归因复杂化。Kbhb不应被视为统一有益或致病性的。相反，其效应取决于供体可用性、位点特异性、读取蛋白参与、组织情境、疾病阶段及竞争性酰化修饰。未来工作应优先开展位点分辨质谱分析、经验证的染色质图谱分析、平行酰化组分析、功能性扰动及临床可解释的生物标志物，以确定哪些Kbhb事件具有因果性且具有治疗可操作性。
Abstract
Lysine β-hydroxybutyrylation (Kbhb) is a β-hydroxybutyrate-derived lysine acylation that connects ketone-body metabolism with chromatin regulation and non-histone protein function. Initially described as a fasting-responsive histone mark, Kbhb is now implicated in immune memory, metabolic adaptation, cancer metabolism and neuroprotection. This Review reframes Kbhb as a context-dependent metabolic acylation system. We discuss the metabolic origin of β-hydroxybutyryl-CoA, the writer, reader and eraser machinery of Kbhb, its crosstalk with acetylation, lactylation and crotonylation, and the evidence standards required to distinguish Kbhb-driven mechanisms from broader β-hydroxybutyrate biology. Recent studies have identified p300/CBP as a Kbhb writer, HDACs and sirtuins as erasers, and ENL as an H3K9bhb reader. Kbhb has also been linked to CD8 T-cell memory, fasting-responsive chromatin remodeling, tumor metabolic rewiring and non-histone protein regulation. However, shared enzymes, overlapping acylation programs and pleiotropic BHB signaling complicate causal attribution. Kbhb should not be viewed as uniformly beneficial or pathological. Instead, its effects depend on donor availability, site specificity, reader engagement, tissue context, disease stage and competing acylations. Future work should prioritize site-resolved mass spectrometry, validated chromatin profiling, parallel acylome analysis, functional perturbation and clinically interpretable biomarkers to define which Kbhb events are causal and therapeutically actionable.
如何引用
AMA
Ce Chen, Xue Chen, Xin Lyu, Ling Yao, Shaowen Ge, Meiling Yu, et al. Lysine β-hydroxybutyrylation: A metabolic-epigenetic interface in health and disease.. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2026; doi:10.1016/j.phymed.2026.158410.
APA
Ce Chen, Xue Chen, Xin Lyu, Ling Yao, Shaowen Ge, Meiling Yu, et al (2026). Lysine β-hydroxybutyrylation: A metabolic-epigenetic interface in health and disease.. Phytomedicine : international journal of phytotherapy and phytopharmacology. https://doi.org/10.1016/j.phymed.2026.158410
GB/T 7714
Ce Chen, Xue Chen, Xin Lyu, Ling Yao, Shaowen Ge, Meiling Yu, et al. Lysine β-hydroxybutyrylation: A metabolic-epigenetic interface in health and disease.[J]. Phytomedicine : international journal of phytotherapy and phytopharmacology, 2026 doi:10.1016/j.phymed.2026.158410.
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