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In
chemistry Chemistry is the scientific Science () is a systematic enterprise that builds and organizes knowledge Knowledge is a familiarity or awareness, of someone or something, such as facts A fact is an occurrence in the real world. T ...

chemistry
, hydroxylation can refer to: *(i) most commonly, hydroxylation describes a
chemical A chemical substance is a form of matter In classical physics and general chemistry, matter is any substance that has mass and takes up space by having volume. All everyday objects that can be touched are ultimately composed of atoms, which ...

chemical
process that introduces a
hydroxyl group A hydroxy or hydroxyl group is a functional group with the chemical formula -OH and composed of one oxygen Oxygen is the chemical element Image:Simple Periodic Table Chart-blocks.svg, 400px, Periodic table, The periodic table of the ...

hydroxyl group
(-OH) into an
organic compound In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the composed of s, s and s: their composition, structure, properties, behavior and the changes they undergo during ...
. *(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 C-H bonds, some reactions ''add'' OH groups to unsaturated substrates. The
Sharpless dihydroxylation Sharpless asymmetric dihydroxylation (also called the Sharpless bishydroxylation) is the chemical reaction A chemical reaction is a process that leads to the chemical transformation of one set of chemical substance A chemical substance is ...
is such a reaction: it converts alkenes into
diol A diol is a chemical compound A chemical compound is a chemical substance composed of many identical molecules (or molecular entity, molecular entities) composed of atoms from more than one chemical element, element held together by chemical ...

diol
s. The hydroxy groups are provided by
hydrogen peroxide Hydrogen peroxide is a chemical compound A chemical compound is a chemical substance composed of many identical molecules (or molecular entity, molecular entities) composed of atoms from more than one chemical element, element held together ...

hydrogen peroxide
, which adds across the double bond of
alkene In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the composed of s, s and s: their composition, structure, properties, behavior and the changes they undergo dur ...

alkene
s.


Biological hydroxylation

In
biochemistry Biochemistry or biological chemistry, is the study of chemical process In a scientific Science () is a systematic enterprise that Scientific method, builds and organizes knowledge in the form of Testability, testable explanations and pr ...

biochemistry
, hydroxylation reactions are often facilitated by
enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates in ...

enzyme
s called hydroxylases. A C-H bond is converted to an alcohol by insertion of an oxygen atom into a C-H 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 O2 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 Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism In biology, an orga ...
since it converts
lipophilic Lipophilicity (from Greek#REDIRECT Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country located in Southeast Europe. Its population is approxi ...
compounds into water-soluble (
hydrophilic A hydrophile is a molecule A molecule is an electrically Electricity is the set of physical phenomena associated with the presence and motion Image:Leaving Yongsan Station.jpg, 300px, Motion involves a change in position In phys ...

hydrophilic
) products that are more readily removed by the
kidneys The kidneys are two reddish-brown bean-shaped organs found in vertebrate Vertebrates () comprise all species of animal Animals (also called Metazoa) are multicellular eukaryotic organisms that form the Kingdom (biology), biological ...
or
liver The liver is an organ Organ may refer to: Biology * Organ (anatomy) An organ is a group of Tissue (biology), tissues with similar functions. Plant life and animal life rely on many organs that co-exist in organ systems. A given organ's t ...

liver
and
excreted Excretion is a process in which metabolic waste Metabolic wastes or excrements are substance Substance may refer to: * Substance (Jainism), a term in Jain ontology to denote the base or owner of attributes * Chemical substance, a material with a ...
. Some
drugs A drug is any chemical substance A chemical substance is a form of matter In classical physics and general chemistry, matter is any substance that has mass and takes up space by having volume. All everyday objects that can be touched ...
(for example,
steroid A steroid is a biologically active organic compound In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the composed of s, s and s: their composition, structure, ...

steroid
s) are activated or deactivated by hydroxylation. The principal hydroxylation agent in nature is
cytochrome P-450 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...
, 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. Func ...
, 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 biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew in 1958, for which they received a No ...

protein
s is
proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid Proteinogenic amino acids are amino acids that are incorporated biosynthetically into proteins during translation (biology), translation. The word "proteinogenic ...

proline
. This is due to the fact that
collagen Collagen () is the main structural protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Cowder ...

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 (C5H9O3N), is an amino acid Amino acids are organic compound In , organic compounds are generally any s that contain - . Due to carbon's ability to (form chains with other carbon s) ...

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 factor Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in available oxygen in the cellular environment, or Hypoxia (medical), hypoxia. Discovery The HIF transcriptional complex was discovered in 1995 by Gregg ...
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 Amino acids are organic compound In , organic compounds are generally any s that contain - . Due to carbon's ability to (form chains with other carbon s), millions of organic compounds are known. Th ...

hydroxylysine
(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 mec ...
,
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 mec ...
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 cofactor (biochemistry), ...
, 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 vitamin A vitamin is an organic molecule , CH4; is among the simplest organic compounds. In chemistry, organic compounds are generally any chemical compounds that contain carb ...

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 disease A disease is a particular abnormal condition that negatively affects the structure A structure is an arrangement and organization of interrelated elements in a material object or system A system is a group of ...
. Since citrus fruits are rich in vitamin C, British
sailor A sailor, seaman, mariner, or seafarer is a person who works aboard a watercraft Watercraft, also known as water vessels or waterborne vessels, are vehicles A vehicle (from la, vehiculum) is a machine A machine is any physical sys ...

sailor
s were given
limes Limes is the plural of lime. It is also the Latin word for ''limit'' which refers to: * Limes (Roman Empire), a border marking and defense system of the ancient Roman Empire * Limes (magazine), ''Limes'' (magazine), an Italian geopolitical magazi ...
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 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 enzy ...
* Dopamine β-hydroxylase *
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 of ...

Phenylalanine hydroxylase
*
Tyrosine hydroxylase -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acid Amino acids are organic compound In , organic compounds are generally any s that contain - . Due to carbon's ability to (form chain ...
* 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 forms of benzene (top) combine to produce an average structure (bottom) In chemistry, aromaticity is a property of cyclic compound, cyclic (ring (chemistry), ring-shaped), ...

hydroquinone
.


References

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