Tyrosine hydroxylase
Encyclopedia
Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme
responsible for catalyzing the conversion of the amino acid
L-tyrosine to dihydroxyphenylalanine
(DOPA). It does so using tetrahydrobiopterin
as a coenzyme. DOPA is a precursor for dopamine
, which, in turn, is a precursor for norepinephrine
(noradrenaline) and epinephrine
(adrenaline). In humans, tyrosine hydroxylase is encoded by the TH gene
.
, is found in the cytosol
of all cells containing catecholamines. This initial reaction is the rate limiting step in the production of catecholamines.
The enzyme is highly specific, not accepting indole
derivatives - which is unusual as many other enzymes involved in the production of catecholamines do.
). This inhibition can lead to a depletion of dopamine and norepinepherine in the brain due to the lack of the precursor L-Dopa (L-3,4-dyhydroxyphenylalanine) which is synthesized by tyrosine hydroxylase. This drug is rarely used and can cause depression, but it is useful in treating pheochromocytoma
and also resistant hypertension
.
Tyrosine hydroxylase is an autoantigen in Autoimmune Polyendocrine Syndrome (APS) type I
.
Older examples of inhibitors mentioned in the literature include oudenone
and aquayamycin
.
TH is decreased by the release of Catecholamines.
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...
responsible for catalyzing the conversion of the amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
L-tyrosine to dihydroxyphenylalanine
Dihydroxyphenylalanine
Dihydroxyphenylalanine may refer to either of two chemical compounds:* D-DOPA, -3,4-dihydroxyphenylalanine* L-DOPA, -3,4-dihydroxyphenylalanine, a precursor of a neurotransmitter...
(DOPA). It does so using tetrahydrobiopterin
Tetrahydrobiopterin
Tetrahydrobiopterin or sapropterin is a naturally occurring essential cofactor of the three aromatic amino acid hydroxylase enzymes, used in the degradation of amino acid phenylalanine and in the biosynthesis of the neurotransmitters serotonin , melatonin, dopamine, norepinephrine ,...
as a coenzyme. DOPA is a precursor for dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
, which, in turn, is a precursor for norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
(noradrenaline) and epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
(adrenaline). In humans, tyrosine hydroxylase is encoded by the TH gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Reaction
The enzyme, an oxygenaseOxygenase
An oxygenase is any enzyme that oxidizes a substrate by transferring the oxygen from molecular oxygen O2 to it. The oxygenases form a class of oxidoreductases; their EC number is EC 1.13 or EC 1.14....
, is found in the cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....
of all cells containing catecholamines. This initial reaction is the rate limiting step in the production of catecholamines.
The enzyme is highly specific, not accepting indole
Indole
Indole is an aromatic heterocyclic organic compound. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring. Indole is a popular component of fragrances and the precursor to many pharmaceuticals. Compounds that contain an...
derivatives - which is unusual as many other enzymes involved in the production of catecholamines do.
Clinical significance
Tyrosine hydroxylase can be inhibited by the drug α-methyl-para-tyrosine (MetirosineMetirosine
Metirosine is an antihypertensive drug. It inhibits the enzyme tyrosine hydroxylase and, therefore, catecholamine synthesis, which, as a consequence, depletes the levels of the catecholamines dopamine, adrenaline and noradrenaline in the body.-Clinical use:Metirosine has been used in the treatment...
). This inhibition can lead to a depletion of dopamine and norepinepherine in the brain due to the lack of the precursor L-Dopa (L-3,4-dyhydroxyphenylalanine) which is synthesized by tyrosine hydroxylase. This drug is rarely used and can cause depression, but it is useful in treating pheochromocytoma
Pheochromocytoma
A pheochromocytoma or phaeochromocytoma is a neuroendocrine tumor of the medulla of the adrenal glands , or extra-adrenal chromaffin tissue that failed to involute after birth and secretes excessive amounts of catecholamines, usually noradrenaline , and adrenaline to a lesser extent...
and also resistant hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
.
Tyrosine hydroxylase is an autoantigen in Autoimmune Polyendocrine Syndrome (APS) type I
Autoimmune polyendocrine syndrome
In medicine, autoimmune polyendocrine syndromes are a heterogeneous group of rare diseases characterised by autoimmune activity against more than one endocrine organs, although non-endocrine organs can be affected....
.
Older examples of inhibitors mentioned in the literature include oudenone
Oudenone
Oudenone is a molecule found in fungus metabolism. It is an inhibitor of the enzyme tyrosine hydroxylase....
and aquayamycin
Aquayamycin
Aquayamycin is an anthraquinone. It is an inhibitor of the enzyme tyrosine hydroxylase....
.
Regulation
TH is increased acutely (minutes) by phosphorylation and chronically (days) by protein synthesis. The phosphorylation can be sustained by nicotine for up to 48 hours.TH is decreased by the release of Catecholamines.