Β-Hydroxybutyric acid

In humans, can be synthesized in the liver via the metabolism of fatty acids (e.g., butyrate), , and ketogenic amino acids through a series of reactions that metabolize these compounds into acetoacetate, which is the first ketone body that is produced in the fasting state. The biosynthesis of from acetoacetate is catalyzed by the β-hydroxybutyrate dehydrogenase enzyme. Butyrate can also be metabolized into via a second metabolic pathway that does not involve acetoacetate as a metabolic intermediate. This metabolic pathway is as follows: :butyrate→butyryl-CoA→crotonyl-CoA→β-hydroxybutyryl-CoA→poly-β-hydroxybutyrate→()→ The last reaction in this metabolic pathway, which involves the conversion of () into , is catalyzed by the hydroxybutyrate-dimer hydrolase enzyme. This elevated β-hydroxybutyrate level is naturally expected, as β-hydroxybutyrate is formed from acetoacetate. The compound can be used as an energy source by the brain and skeletal muscle when blood glucose is low. Diabetic patients can have their ketone levels tested via urine or blood to indicate diabetic ketoacidosis. In alcoholic ketoacidosis, this ketone body is produced in greatest concentration. Ketogenesis occurs if oxaloacetate in the liver cells is depleted, a circumstance created by reduced carbohydrate intake (through diet or starvation); prolonged, excessive alcohol consumption; and/or insulin deficiency. Because oxaloacetate is crucial for entry of acetyl-CoA into the TCA cycle, the rapid production of acetyl-CoA from fatty acid oxidation in the absence of ample oxaloacetate overwhelms the decreased capacity of the TCA cycle, and the resultant excess of acetyl-CoA is shunted towards ketone body production. ==Biological activity==

D-β-Hydroxybutyric acid, along with butyric acid, are the two primary endogenous agonists of hydroxycarboxylic acid receptor 2 (HCA2), a GPCR. β-Hydroxybutyrate is primarily carried via two classes of transporters: monocarboxylate transporters (MCTs) and sodium-coupled monocarboxylate transporters (SMCTs). MCTs enable keton bodies like β-hydroxybutyrate to enter extrahepatic tissues, like the brain, muscle and kidneys, while SMCTs (which co-transport sodium) are found in the kidneys, intestines, and certain neurones. Evidence suggests that MCT1 deficiency can lead to recurrent ketoacidosis. β-Hydroxybutyric acid is able to cross the blood-brain-barrier into the central nervous system. Levels of β-hydroxybutyric acid increase in the liver, heart, muscle, brain, and other tissues with exercise, calorie restriction, fasting, and ketogenic diets. ==Laboratory and industrial chemistry==

β-Hydroxybutyric acid is the precursor to polyesters, which are biodegradable plastics. This polymer, poly(3-hydroxybutyrate), is also naturally produced by the bacteria Alcaligenes eutrophus. β-Hydroxybutyrate can be extracted from poly(3-hydroxybutyrate) by acid hydrolysis. The concentration of in blood plasma is measured through a test that uses β-hydroxybutyrate dehydrogenase, with NAD+ as an electron-accepting cofactor. The conversion of to acetoacetate, which is catalyzed by this enzyme, reduces the NAD+ to NADH, generating an electrical change; the magnitude of this change can then be used to extrapolate the amount of in the sample. == See also ==