Around 40% of dietary is converted to , which is subsequently used in the synthesis of other compounds. The vast majority of metabolism is initially catalyzed by the branched-chain amino acid aminotransferase enzyme, producing (α-KIC). α-KIC is mostly metabolized by the mitochondrial enzyme branched-chain dehydrogenase, which converts it to isovaleryl-CoA. Isovaleryl-CoA is subsequently metabolized by isovaleryl-CoA dehydrogenase and converted to , which is used in the synthesis of acetyl-CoA and other compounds. During biotin deficiency, HMB can be synthesized from via enoyl-CoA hydratase and an unknown thioesterase enzyme, which convert into and into HMB respectively. A relatively small amount of α-KIC is metabolized in the liver by the cytosolic enzyme 4-hydroxyphenylpyruvate dioxygenase (KIC dioxygenase), which converts α-KIC to HMB. In healthy individuals, this minor pathway – which involves the conversion of to α-KIC and then HMB – is the predominant route of HMB synthesis. Chemistry acid is a monocarboxylic β-hydroxy acid and natural product with the molecular formula . At room temperature, pure acid occurs as a transparent, colorless to light yellow liquid which is soluble in water. acid is a weak acid with a pKa of 4.4. Its refractive index () is 1.42. Chemical structure acid is a member of the carboxylic acid family of organic compounds. It is a structural analog of butyric acid with a hydroxyl functional group and a methyl substituent located on its beta carbon. By extension, other structural analogs include acid and acid. Synthesis A variety of synthetic routes to acid have been developed. The first reported chemical syntheses approached HMB by oxidation of alkene, vicinal diol, and alcohol precursors: in 1877, Russian chemists Michael and Alexander Zaytsev reported the preparation of HMB by oxidation of 2-methylpent-4-en-2-ol with chromic acid (H2CrO4); in 1880 and 1889, Schirokoff and Reformatsky (respectively) reported that the oxidative cleavage of the vicinal diol 4-methylpentane-1,2,4-triol with acidified potassium permanganate (KMnO4) yields HMB – this result is closest related to the first synthesis as cold dilute KMnO4 oxidises alkenes to vicinal cis-diols which hot acid KMnO4 further oxidises to carbonyl-containing compounds, and the diol intermediate is not obtained when hot acidic conditions are used for alkene oxidation. In other words, racemic 4-methylpentane-1,2,4-triol is a derivative of 2-methylpent-4-en-2-ol and β-hydroxy β-methylbutyric acid is a derivative of both; and, in 1892, Kondakow reported the preparation of HMB by permanganate oxidation of 3-methylbutane-1,3-diol. Depending on the experimental conditions, cycloaddition of acetone and ketene produces