(S)-3-Hydroxybutyrate (sodium salt) is a raw material used for synthesizing fine chemicals with optical activity. It is usually synthesized from acetyl coenzyme A, and this process is catalyzed by β-hydroxybutyrate dehydrogenase [1-2]. (S)-3-Hydroxybutyrate is the enantiomer of the naturally occurring ketone body β-hydroxybutyric acid, and the latter is the (R) isomer [3]. (S)-3-Hydroxybutyrate exists as a metabolite in the human body and is commonly seen in ketosis. (S)-3-Hydroxybutyrate plays an important intermediate role in the synthesis of various compounds such as amino acids, fatty acids, and carbohydrates. In laboratory applications, (S)-3-Hydroxybutyrate is widely used to study the effects of metabolic processes on different cell types [4].
In vitro, (S)-3-Hydroxybutyrate (0, 5, 10, 20, 40, 80, 160μM; 6, 12, 18, 24, 30h) treatment enhanced the cell viability of mouse hippocampal neuron cells (HT22) with glucose deficiency, decreased the expression of phosphorylated Tau protein and increased the expression of mtDNA-CN and maintained the mitochondrial morphology [5]. (S)-3-Hydroxybutyrate (10mM; 48h) treatment significantly reduced the percentage of apoptosis in mouse glial cells and increased the concentration of Ca2+ in the cytoplasm [6].
In vivo, (S)-3-Hydroxybutyrate (25, 50, and 100mg/kg/day; 21 days; oral) treatment significantly inhibited the loss of muscle weight, muscle fiber size, and muscle fiber diameter in the hind limb empty-load mouse model, and promoted positive balance of proteins and nucleotides, enhanced glutamate accumulation and reduced uric acid consumption in the muscles [7]. (S)-3-Hydroxybutyrate (150mg/day; 5 days; s.c.) treatment could safely prevent muscle weakness in septic mice without increasing the incidence or mortality risk. However, doses of 180mg/day and higher would cause significant metabolic alkalosis and hypernatremia as well as increased markers of kidney injury in mice [8].
References:
[1] Tseng, H.-C., Martin, C.H., Nielsen, D.R., et al. Metabolic engineering of Escherichia coli for enhanced production of (R)- and (S)-3-hydroxybutyrate. Appl. Environ. Microbiol. 75(10), 3137-3145 (2009).
[2] Ploux O, Masamune S, Walsh CT. The NADPH-linked acetoacetyl-CoA reductase from Zoogloea ramigera. Characterization and mechanistic studies of the cloned enzyme over-produced in Escherichia coli. Eur J Biochem. 1988 May 16;174(1):177-82.
[3] Budin N, Higgins E, DiBernardo A, et al. Efficient synthesis of the ketone body ester (R)-3-hydroxybutyryl-(R)-3-hydroxybutyrate and its (S, S) enantiomer[J]. Bioorganic Chemistry, 2018, 80: 560-564.
[4] Mierziak J, Burgberger M, Wojtasik W. 3-Hydroxybutyrate as a metabolite and a signal molecule regulating processes of living organisms[J]. Biomolecules, 2021, 11(3): 402.
[5] Hu X, Lin Y, Huang K, et al. 3-Hydroxybutyrate, a metabolite in sustaining neuronal cell vitality: a mendelian randomization and in vitro experimentation[J]. Nutrition & Metabolism, 2025, 22(1): 75.
[6] Xiao XQ, Zhao Y, Chen GQ. The effect of 3-hydroxybutyrate and its derivatives on the growth of glial cells. Biomaterials. 2007;28(25):3608-3616.
[7] Chen J, Li Z, Zhang Y, et al. Mechanism of reduced muscle atrophy via ketone body (D)-3-hydroxybutyrate[J]. Cell & Bioscience, 2022, 12(1): 94.
[8] Weckx R, Goossens C, Derde S, et al. Identification of the toxic threshold of 3-hydroxybutyrate-sodium supplementation in septic mice[J]. BMC Pharmacology and Toxicology, 2021, 22(1): 50.
(S)-3-Hydroxybutyrate (sodium salt)是一种用于合成具有光学活性的精细化学品的原料，通常由乙酰辅酶A合成，这一过程由β-羟基丁酸脱氢酶催化完成 [1-2]。(S)-3-Hydroxybutyrate是天然存在的酮体β-羟基丁酸的对映体，而后者是（R）异构体 [3]。(S)-3-Hydroxybutyrate在人体内作为一种代谢物存在，在酮症中常见。(S)-3-Hydroxybutyrate在合成如氨基酸、脂肪酸和碳水化合物等各种化合物方面起着重要的中间作用。在实验室应用中，(S)-3-Hydroxybutyrate被广泛用于研究代谢过程对不同细胞类型的影响 [4]。
在体外，(S)-3-Hydroxybutyrate（0, 5, 10, 20, 40, 80, 160μM; 6, 12, 18, 24, 30h）处理增强了葡萄糖缺乏的小鼠海马神经元细胞（HT22）的细胞活力，降低磷酸化Tau蛋白表达和增加mtDNA-CN的表达并维持线粒体形态 [5]。(S)-3-Hydroxybutyrate（10mM; 48h）处理显著降低了小鼠胶质细胞的凋亡百分比，并提高了细胞质中Ca2+的浓度 [6]。
在体内，(S)-3-Hydroxybutyrate（25, 50, and 100mg/kg/day; 21 days; oral）治疗显著抑制了后肢空载小鼠模型中肌肉重量、肌纤维大小和肌纤维直径的损失，并促进蛋白质和核苷酸的正平衡，增强谷氨酸的积累并降低肌肉中的尿酸消耗 [7]。(S)-3-Hydroxybutyrate（150mg/day; 5 days; s.c.）治疗能够安全预防脓毒症小鼠的肌肉无力，而不会增加发病率或死亡风险。而180mg/天及更高的剂量会导致小鼠发生明显的代谢性碱中毒和高钠血症以及肾损伤标志物增加 [8]。