3-hydroxybutyrate dehydrogenase (BDH) (BDH)

3-hydroxybutyrate dehydrogenase (BDH) is a critical enzyme in ketone body metabolism, primarily existing in humans as the mitochondrial isoform BDH1 and the cytosolic isoform BDH2 [1, 5]. BDH1 catalyzes the reversible, NAD+-dependent interconversion of (R)-3-hydroxybutyrate and acetoacetate, serving as a key regulator of energy homeostasis during periods of glucose scarcity, such as fasting or intense exercise [3, 8]. It is the final step of ketogenesis in the liver and the first step of ketolysis in peripheral tissues like the heart, brain, and skeletal muscle [1, 4]. Beyond its metabolic role, BDH1 is involved in regulating oxidative stress, inflammation, and apoptosis, often through the activation of the Nrf2 signaling pathway [4, 16]. The enzyme has emerged as a promising therapeutic target for metabolic disorders such as fatty liver disease and type 2 diabetes, as well as certain cancers and cardiomyopathies [4, 9, 16]. While direct pharmacological modulators are largely in the experimental stage, the enzyme's activity is influenced by ketogenic diets and exogenous ketone supplements, which are being explored for their therapeutic potential in various metabolic and neurodegenerative conditions [12, 14, 19].

Other names

3-HBDHHBDHD-beta-hydroxybutyrate dehydrogenaseBDH1BDH2Mitochondrial 3-hydroxybutyrate dehydrogenaseCytosolic 3-hydroxybutyrate dehydrogenase

Catalyzes the reversible NAD+-dependent interconversion of (R)-3-hydroxybutyrate and acetoacetate, facilitating ketone body synthesis in the liver and utilization in peripheral tissues as an alternative energy source.