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In chemistry, hydroxylation can refer to: *(i) most commonly, hydroxylation describes a chemical process that introduces a
hydroxyl group In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...
() 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. The s ...
. *(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 Sharpless asymmetric dihydroxylation (also called the Sharpless bishydroxylation) is the chemical reaction of an alkene with osmium tetroxide in the presence of a chiral quinine ligand to form a vicinal diol. The reaction has been applied to alke ...
is such a reaction: it converts alkenes into
diol A diol is a chemical compound containing two hydroxyl groups ( groups). An aliphatic diol is also called a glycol. This pairing of functional groups is pervasive, and many subcategories have been identified. The most common industrial diol is e ...
s. 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%–6 ...
, 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, a ...
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 Lipophilicity (from Greek λίπος "fat" and φίλος "friendly"), refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such non-polar solvents are themselves lipoph ...
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 no ...
) products that are more readily removed by the
kidneys The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
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 Excretion is a process in which metabolic waste is eliminated from an organism. In vertebrates this is primarily carried out by the lungs, kidneys, and skin. This is in contrast with secretion, where the substance may have specific tasks after lea ...
. Some
drugs A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhalati ...
(for example,
steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and ...
s) are activated or deactivated by hydroxylation. The principal hydroxylation agent in nature is
cytochrome P-450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various comp ...
, hundreds of variations of which are known. Other hydroxylating agents include flavins,
alpha-ketoglutarate-dependent hydroxylases Alpha-ketoglutarate-dependent hydroxylases are a major class of non-heme iron proteins that catalyse a wide range of reactions. These reactions include hydroxylation reactions, demethylations, ring expansions, ring closures, and desaturations. Fun ...
, 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 proteins is
proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...
. 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 wa ...
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 kn ...
(Hyl). These three reactions are catalyzed by very large, multi-subunit enzymes
prolyl 4-hydroxylase Procollagen-proline dioxygenase, commonly known as prolyl hydroxylase, is a member of the class of enzymes known as alpha-ketoglutarate-dependent hydroxylases. These enzymes catalyze the incorporation of oxygen into organic substrates through a me ...
,
prolyl 3-hydroxylase Procollagen-proline dioxygenase, commonly known as prolyl hydroxylase, is a member of the class of enzymes known as alpha-ketoglutarate-dependent hydroxylases. These enzymes catalyze the incorporation of oxygen into organic substrates through a me ...
and lysyl 5-hydroxylase, respectively. These reactions require iron (as well as molecular oxygen and α-ketoglutarate) to carry out the oxidation, and use
ascorbic acid Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) and ...
(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 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, decreased red blood cells, gum disease, changes to hair, and bleeding ...
. 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 Limes may refer to: * the plural form of lime (disambiguation) * the Latin word for ''limit'' which refers to: ** Limes (Roman Empire) (Latin, singular; plural: ) is a modern term used primarily for the Germanic border defence or delimiting ...
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 Cytochrome P450 17A1 (steroid 17α-monooxygenase, 17α-hydroxylase, 17-alpha-hydroxylase, 17,20-lyase, 17,20-desmolase) is an enzyme of the hydroxylase type that in humans is encoded by the ''CYP17A1'' gene on chromosome 10. It is ubiquitously ex ...
*
Cholesterol 7 alpha-hydroxylase Cholesterol 7 alpha-hydroxylase also known as cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1) is an enzyme that in humans is encoded by the gene which has an important role in cholesterol metabolism. It is a cytochrome P450 enz ...
*
Dopamine β-hydroxylase Dopamine beta-hydroxylase (DBH), also known as dopamine beta-monooxygenase, is an enzyme () that in humans is encoded by the DBH gene. Dopamine beta-hydroxylase catalyzes the conversion of dopamine to norepinephrine. The three substrates of ...
*
Phenylalanine hydroxylase Phenylalanine hydroxylase. (PAH) () is an enzyme that catalyzes the hydroxylation of the aromatic side-chain of phenylalanine to generate tyrosine. PAH is one of three members of the biopterin-dependent aromatic amino acid hydroxylases, a class ...
*
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 ...
* 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 ''para'' ...
.


References

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