Hydroxylation
Encyclopedia
Hydroxylation is a chemical
process that introduces a hydroxyl group (-OH) into an organic compound
. In biochemistry
, hydroxylation reactions are often facilitated by enzyme
s called hydroxylases. Hydroxylation is the first step in the oxidative degradation of organic compounds in air. It is extremely important in detoxification since hydroxylation converts lipophilic compounds into water-soluble (hydrophilic) products that are more readily excreted. Some drugs (e.g. steroid
s) are activated or deactivated by hydroxylation.
s is proline
. The hydroxylation occurs at the γ-C atom, forming hydroxyproline
(Hyp), an essential element of collagen
, in turn a necessary element of connective tissue
. 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. Lysine may also be hydroxylated on its δ-C atom, forming hydroxylysine
(Hyl).
These three reactions are catalyzed by very large, multi-subunit enzymes prolyl 4-hydroxylase, prolyl 3-hydroxylase 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) to return the iron to its oxidized state. 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 sailor
s were given limes
to combat scurvy on long ocean voyages; hence, they were called "limeys".
Chemistry
Chemistry is the science of matter, especially its chemical reactions, but also its composition, structure and properties. Chemistry is concerned with atoms and their interactions with other atoms, and particularly with the properties of chemical bonds....
process that introduces a hydroxyl group (-OH) into an organic compound
Organic compound
An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...
. In biochemistry
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
, hydroxylation reactions are often facilitated by enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s called hydroxylases. Hydroxylation is the first step in the oxidative degradation of organic compounds in air. It is extremely important in detoxification since hydroxylation converts lipophilic compounds into water-soluble (hydrophilic) products that are more readily excreted. Some drugs (e.g. steroid
Steroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
s) are activated or deactivated by hydroxylation.
Chemical concepts
The hydroxylation process involves conversion of a CH group into a COH group. Hydroxylation is an oxidative process. The oxygen that is inserted into the C-H bond is usually derived from atmospheric oxygen (O2). Since O2 itself is a slow hydroxylating agent, catalysts are required to accelerate the pace of the process.Biological hydroxylation
The principal hydroxylation agent in nature is cytochrome P-450, hundreds of variations of which are known.Other hydroxylating agents include flavins.Hydroxylation of proteins
The principal residue to be hydroxylated in proteinProtein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s is proline
Proline
Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...
. The hydroxylation occurs at the γ-C atom, forming hydroxyproline
Hydroxyproline
-4-Hydroxyproline, or L-hydroxyproline , is a common non-proteinogenic amino acid, abbreviated as HYP, e.g., in Protein Data Bank.-Structure and discovery:...
(Hyp), an essential element of collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
, in turn a necessary element of connective tissue
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...
. Proline hydroxylation is also a vital component of hypoxia
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
response via hypoxia inducible factors. 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
5-Hydroxylysine is an amino acid with the molecular formula C6H14N2O3. It was first discovered in 1921 by Donald Van Slyke. It is a hydroxy derivative of lysine. It is most widely known as a component of collagen....
(Hyl).
These three reactions are catalyzed by very large, multi-subunit enzymes prolyl 4-hydroxylase, prolyl 3-hydroxylase 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
Ascorbic acid
Ascorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
(vitamin C) to return the iron to its oxidized 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
Scurvy is a disease resulting from a deficiency of vitamin C, which is required for the synthesis of collagen in humans. The chemical name for vitamin C, ascorbic acid, is derived from the Latin name of scurvy, scorbutus, which also provides the adjective scorbutic...
. Since citrus fruits are rich in vitamin C, British sailor
Sailor
A sailor, mariner, or seaman is a person who navigates water-borne vessels or assists in their operation, maintenance, or service. The term can apply to professional mariners, military personnel, and recreational sailors as well as a plethora of other uses...
s were given limes
Lime (fruit)
Lime is a term referring to a number of different citrus fruits, both species and hybrids, which are typically round, green to yellow in color, 3–6 cm in diameter, and containing sour and acidic pulp. Limes are a good source of vitamin C. Limes are often used to accent the flavors of foods and...
to combat scurvy on long ocean voyages; hence, they were called "limeys".
Examples of hydroxylases
- 17α-Hydroxylase
- Cholesterol 7 alpha-hydroxylaseCholesterol 7 alpha-hydroxylaseCholesterol 7 alpha-hydroxylase also known as cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 is an enzyme that in humans is encoded by the CYP7A1 gene.- Function :...
- Dopamine β-hydroxylase
- Phenylalanine hydroxylasePhenylalanine hydroxylasePhenylalanine hydroxylase is an enzyme that catalyzes the hydroxylation of the aromatic side-chain of phenylalanine to generate tyrosine. PheOH is one of three members of the pterin-dependent amino acid hydroxylases, a class of monooxygenase that uses tetrahydrobiopterin and a non-heme iron for...
- Tyrosine hydroxylaseTyrosine hydroxylaseTyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to dihydroxyphenylalanine . It does so using tetrahydrobiopterin as a coenzyme. DOPA is a precursor for dopamine, which, in turn, is a precursor for norepinephrine ...