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In
chemistry Chemistry is the scientific study of the properties and behavior of matter. It is a natural science that covers the elements that make up matter to the compounds made of atoms, molecules and ions: their composition, structure, proper ...
, hydroxylation can refer to: *(i) most commonly, hydroxylation describes a chemical process that introduces a hydroxyl group () into an
organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...
. *(ii) the ''degree of hydroxylation'' refers to the number of OH groups in a molecule. The ''pattern of hydroxylation'' refers to the location of hydroxy groups on a molecule or material.


Hydroxylation reactions


Synthetic hydroxylations

Installing hydroxyl groups into organic compounds can be effected by various metal catalysts. Many such catalysts are biomimetic, i.e. they are inspired by or intended to mimic 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 diols. The hydroxy groups are provided by
hydrogen peroxide Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3 ...
, which adds across the double bond of
alkene In organic chemistry, an alkene is a hydrocarbon containing a carbon–carbon double bond. Alkene is often used as synonym of olefin, that is, any hydrocarbon containing one or more double bonds.H. Stephen Stoker (2015): General, Organic ...
s.


Biological hydroxylation

In
biochemistry Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology and ...
, hydroxylation reactions are often facilitated by
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s called hydroxylases. A bond is converted to an alcohol by insertion of an oxygen atom into a bond. Typical stoichiometries for the hydroxylation of a generic hydrocarbon are these: :2R3C-H + O2 -> 2R3C-OH :R3C-H + O2 + 2e- + 2H+ -> R3C-OH + H2O Since itself is a slow and unselective hydroxylating agent, catalysts are required to accelerate the pace of the process and to introduce selectivity. Hydroxylation is often the first step in the degradation of organic compounds in air. Hydroxylation is important in
detoxification Detoxification or detoxication (detox for short) is the physiological or medicinal removal of toxic substances from a living organism, including the human body, which is mainly carried out by the liver. Additionally, it can refer to the period of ...
since it converts lipophilic compounds into water-soluble (
hydrophilic A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are n ...
) products that are more readily removed by the kidneys or
liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...
and excreted. Some drugs (for example, steroids) are activated or deactivated by hydroxylation. The principal hydroxylation agent in nature is cytochrome P-450, hundreds of variations of which are known. Other hydroxylating agents include flavins, alpha-ketoglutarate-dependent hydroxylases, and some diiron hydroxylases.


Of proteins

The hydroxylation of proteins occurs as a post-translational modification, and is catalyzed by 2-oxoglutarate-dependent dioxygenases. When molecules are hydroxylated, they become more water‐soluble, which affects their structure and function. It can take place on several amino acids, like lysine, asparagine, aspartate and histidine, but the most frequently hydroxylated amino acid residue in human
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s is proline. This is due to the fact that 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 (2''S'',4''R'')-4-Hydroxyproline, or L-hydroxyproline ( C5 H9 O3 N), is an amino acid, abbreviated as Hyp or O, ''e.g.'', in Protein Data Bank. Structure and discovery In 1902, Hermann Emil Fischer isolated hydroxyproline from hydrolyzed gelatin ...
(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 factor Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in available oxygen in the cellular environment, or hypoxia. They are only present in parahoxozoan animals. Discovery The HIF transcriptional complex ...
s. In some cases, proline may be hydroxylated instead on its β-C atom. Lysine may also be hydroxylated on its δ-C atom, forming
hydroxylysine Hydroxylysine (Hyl) is an amino acid with the molecular formula C6H14N2O3. It was first discovered in 1921 by Donald Van Slyke as the 5-hydroxylysine form. It arises from a post-translational hydroxy modification of lysine. It is most widely kno ...
(Hyl). These three reactions are catalyzed by very large, multi-subunit enzymes prolyl 4-hydroxylase, prolyl 3-hydroxylase and
lysyl 5-hydroxylase Lysyl hydroxylases (or procollagen-lysine 5-dioxygenases) are alpha-ketoglutarate-dependent hydroxylases enzymes that catalyze the hydroxylation of lysine to hydroxylysine. Lysyl hydroxylases require iron and vitamin C as cofactors for their oxi ...
, respectively. These reactions require iron (as well as molecular oxygen and α-ketoglutarate) to carry out the oxidation, and use ascorbic acid (vitamin C) to return the iron to its reduced state. Deprivation of ascorbate leads to deficiencies in proline hydroxylation, which leads to less stable collagen, which can manifest itself as the disease
scurvy Scurvy is a deficiency disease, disease resulting from a lack of vitamin C (ascorbic acid). Early symptoms of deficiency include weakness, feeling tired and sore arms and legs. Without treatment, anemia, decreased red blood cells, gum disease, ch ...
. Since citrus fruits are rich in vitamin C, British
sailor A sailor, seaman, mariner, or seafarer is a person who works aboard a watercraft as part of its crew, and may work in any one of a number of different fields that are related to the operation and maintenance of a ship. The profession of the s ...
s were given limes to combat scurvy on long ocean voyages; hence, they were called "limeys". Several endogenous proteins contain hydroxyphenylalanine and hydroxytyrosine residues. These residues are formed due to the hydroxylation of phenylalanine and tyrosine, a process in which the hydroxylation converts phenylalanine residues into tyrosine residues. This is very important in living organisms to help them control excess amounts of phenylalanine residues. Hydroxylation of tyrosine residues is also very vital in living organisms because hydroxylation at C-3 of tyrosine creates 3,4- dihydroxy phenylalanine (DOPA), which is a precursor to hormones and can be converted into dopamine.


Examples

* 17α-Hydroxylase * Cholesterol 7 alpha-hydroxylase * Dopamine β-hydroxylase * Phenylalanine hydroxylase *
Tyrosine hydroxylase Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA). It does so using molecular oxygen (O2), as well as iron (Fe2+) and t ...
* One example of non-biological hydroxylation is the hydrogen peroxide hydroxylation of phenol to form
hydroquinone Hydroquinone, also known as benzene-1,4-diol or quinol, is an aromatic organic compound that is a type of phenol, a derivative of benzene, having the chemical formula C6H4(OH)2. It has two hydroxyl groups bonded to a benzene ring in a ''pa ...
.


References

{{Protein posttranslational modification Organic redox reactions Post-translational modification