D-alpha-hydroxybutyrate

D-alpha-hydroxybutyrate (DAHB), also known as (R)-2-hydroxybutyrate, is a naturally occurring short-chain alpha-hydroxy acid of microbial origin that acts as an immunometabolic signaling molecule. Developed by researchers at Memorial Sloan Kettering Cancer Center, DAHB has been shown to enhance the antitumor activity of cytotoxic CD8+ T cells. Mechanistically, DAHB signaling switches T cell cellular bioenergetics from glycolysis to oxidative phosphorylation supported by fatty acid oxidation, which suppresses AMPK phosphorylation and the integrated stress response (ISR) while significantly elevating phosphocreatine (PCr) levels. This bioenergetic reserve supports ATP-dependent chromatin remodeling at effector gene loci (such as Prf1, Ifng, and Tnf) via the BAF (mSWI/SNF) complex, driving T cell differentiation into cytotoxic effector cells. Additionally, oral administration of DAHB has been shown to limit diet-induced weight gain through a mechanism requiring lactate dehydrogenase D (LDHD) in the intestinal epithelium, where it is oxidized to alpha-ketobutyrate.

Other names

(R)-2-hydroxybutanoic acid(R)-2-hydroxybutyrate(R)-2-hydroxybutyric acidD-2-hydroxybutanoic acidD2-hydroxybutanoic acidD 2-hydroxybutanoic acidD-2-hydroxybutyrateD2-hydroxybutyrateD 2-hydroxybutyrateD-2-hydroxybutyric acidD2-hydroxybutyric acidD 2-hydroxybutyric acidD-alpha-hydroxybutyric acidD-α-hydroxybutyrateD-α-hydroxybutyric acidDAHB