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In chemistry, hydroxylation refers to the installation of a hydroxyl group () into an organic compound. Hydroxylations generate alcohols and phenols, which are very common . Hydroxylation confers some degree of water-solubility. Hydroxylation of a hydrocarbon is an oxidation, thus a step in degradation.
Hydroxylation is often the first step in the degradation of organic compounds in air. Hydroxylation is important in detoxification since it converts lipophilicity compounds into water-soluble (hydrophile) products that are more readily removed by the kidneys or liver and excretion. Some drugs (for example, ) are activated or deactivated by hydroxylation.
The principal hydroxylation catalyst in nature is cytochrome P-450, hundreds of variations of which are known. Other hydroxylating agents include flavins, alpha-ketoglutarate-dependent hydroxylases (2-oxoglutarate-dependent dioxygenases), and some diiron hydroxylases.Nelson, D. L.; Cox, M. M. "Lehninger, Principles of Biochemistry" 3rd Ed. Worth Publishing: New York, 2000. .
The most frequently hydroxylated amino acid residue in human is proline. This is because collagen makes up about 25–35% of the protein in our bodies and contains a hydroxyproline at almost every 3rd residue in its amino acid sequence. Collagen consists of both 3‐hydroxyproline and 4‐hydroxyproline residues. Hydroxylation occurs at the γ-C atom, forming hydroxyproline (Hyp), which stabilizes the secondary structure of collagen due to the strong electronegative effects of oxygen. Proline hydroxylation is also a vital component of hypoxia response via hypoxia inducible factors. In some cases, proline may be hydroxylated instead on its β-C atom. These three reactions are catalyzed by large, multi-subunit enzymes prolyl 4-hydroxylase, prolyl 3-hydroxylase, and lysyl 5-hydroxylase, respectively. These enzymes require iron (as well as molecular oxygen and α-ketoglutarate). They consume oxygen (the oxidant) and ascorbic acid (vitamin C, the reductant). Deprivation of ascorbate leads to deficiencies in proline hydroxylation, which leads to less stable collagen, which can manifest itself as the disease scurvy. Since citrus fruits are rich in vitamin C, British were given limes to combat scurvy on long ocean voyages; hence, they were called "". (2025). 9781119451662, Wiley. ISBN 9781119451662
Several other amino acids aside from proline are susceptible to hydroxylation, especially lysine, asparagine, aspartate and histidine. Lysine may be hydroxylated on its δ-C atom, forming hydroxylysine (Hyl). Several endogenous proteins contain hydroxyphenylalanine and hydroxytyrosine residues. These residues are formed by hydroxylation of phenylalanine and tyrosine, a process in which the hydroxylation converts phenylalanine residues into tyrosine residues. Hydroxylation at C-3 of tyrosine gives 3,4- dihydroxyphenylalanine (DOPA), which is a precursor to hormones and can be converted into dopamine.
Installing hydroxyl groups into organic compounds can be effected by biomimetic catalysts, i.e. catalysts whose design is inspired by enzymes such as cytochrome P450.
Whereas many hydroxylations insert O atoms into bonds, some reactions add OH groups to unsaturated substrates. The Sharpless dihydroxylation is such a reaction: it converts alkenes into . The hydroxy groups are provided by hydrogen peroxide, which adds across the double bond of .
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