3-Hydroxybutyric acid (CAS: 300-85-6), also known as beta-hydroxybutanoic acid, is a typical partial-degradation product of branched-chain amino acids (primarily valine) released from muscle for hepatic and renal gluconeogenesis. This acid is metabolized by 3-hydroxybutyrate dehydrogenase (catalyzes the oxidation of 3-hydroxybutyrate to form acetoacetate, using NAD+ as an electron acceptor). In the liver mitochondrial matrix, the enzyme can also catalyze the reverse reaction, a step in ketogenesis. Hepatocytes are the main cell type in the liver (~80%). Blood glucose enters hepatocytes via GLUT2 and GLUT8, a plasma membrane glucose transporter. Glucose is metabolized into pyruvate through glycolysis in the cytoplasm, and pyruvate is completely oxidized to generate ATP through the TCA cycle and oxidative phosphorylation in the mitochondria. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Ketone synthesis in the liver produces acetoacetate and beta-hydroxybutyrate from two acetyl CoA molecules. Acetyl-CoA is a metabolite derived from glucose, fatty acid, and amino acid catabolism. During glycolysis, glucose is broken down into two three-carbon molecules of pyruvate. The mitochondrial pyruvate dehydrogenase complex then catalyzes the oxidative decarboxylation of pyruvate to produce acetyl-CoA, a two-carbon acetyl unit that is ligated to the acyl-group carrier, CoA. Under fasted or survival states, acetyl-CoA is channeled into the mitochondria for synthesis of ATP and ketone bodies. Mitochondrial amounts of acetyl-CoA increase relative to nucleocytosolic amounts. Fatty acid oxidation significantly increases mitochondrial acetyl-CoA. β-hydroxybutyrate (not technically a ketone according to IUPAC nomenclature) is generated through the action of the enzyme D-β-hydroxybutyrate dehydrogenase on acetoacetate. Upon entering the tissues, beta-hydroxybutyrate is converted by D-β-hydroxybutyrate dehydrogenase back to acetoacetate along with a proton and a molecule of NADH, the latter of which goes on to power the electron transport chain and other redox reactions. β-Hydroxybutyrate is the most abundant of the ketone bodies, followed by acetoacetate and finally acetone

Metabolism and Physiological Effects of β-Hydroxybutyric acid References