D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1)

D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1), is a **mitochondrial enzyme** belonging to the short chain dehydrogenase/reductase superfamily, responsible for **catalyzing the reversible interconversion of acetoacetate and (R)-3-hydroxybutyrate**, which are major ketone bodies produced during fatty acid catabolism[1][2][3][5]. BDH1 is essential for ketogenesis, particularly during **fasting, ketogenic diets, or prolonged exercise**, helping to balance mitochondrial redox status and support glucose production[3][5]. BDH1 activity depends on phosphatidylcholine for optimal function and forms a homotetrameric structure localized to the mitochondrial membrane[3][5]. Functionally, it plays a key role in systemic energy homeostasis and influences disease states including cardiovascular, metabolic, neurological, and cancer-related disorders, partly through its regulation of beta-hydroxybutyrate, an important metabolic signaling molecule involved in **epigenetic modifications** such as histone β-hydroxybutyrylation[6]. Drugs that influence BDH1 or beta-hydroxybutyrate levels are being studied in metabolic and inflammatory contexts[6]. BDH1 is considered a **therapeutic enzyme target** in metabolic medicine and is under investigation as a player and biomarker in diverse human diseases.

Other names

3-hydroxybutyrate dehydrogenase 1BDH1BDHSDR9C1(R)-3-hydroxybutyrate dehydrogenaseD-beta-hydroxybutyrate dehydrogenase, mitochondrial3-hydroxybutyrate dehydrogenase (heart, mitochondrial)3-hydroxybutyrate dehydrogenase, type 1Short chain dehydrogenase/reductase family 9C member 1Epididymis secretory sperm binding protein

Drugs like empagliflozin and dapagliflozin elevate β-hydroxybutyrate and modulate BDH1 activity/metabolic signaling Beta-hydroxybutyrate acts as substrate and metabolic regulator; inhibits class I histone deacetylases as a metabolite BDH1 function impacts post-translational epigenetic modifications (β-hydroxybutyrylation) with transcriptional consequences for disease