Tryptophan hydroxylase (TPH) is an

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 ...

() involved in the synthesis of the neurotransmitter serotonin. Tyrosine 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 ...

, and tryptophan hydroxylase together constitute the family of biopterin-dependent aromatic amino acid hydroxylases. TPH catalyzes the following chemical reaction : L-

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic ...

tetrahydrobiopterin Tetrahydrobiopterin (BH4, THB), also known as sapropterin (INN), is a 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 ...

+ O₂

\rightleftharpoons

5-Hydroxytryptophan +

dihydrobiopterin Dihydrobiopterin (BH2) is a pteridine compound produced in the synthesis of L-DOPA, dopamine, serotonin, norepinephrine and epinephrine. It is restored to the required cofactor tetrahydrobiopterin by dihydrobiopterin reductase. See also * Pt ...

+ H₂O It employs one additional cofactor,

iron Iron () is a chemical element with Symbol (chemistry), symbol Fe (from la, Wikt:ferrum, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 element, group 8 of the periodic table. It is, Abundanc ...

Function

It is responsible for addition of the -OH group ( hydroxylation) to the 5 position to form the

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...

5-hydroxytryptophan (5-HTP), which is the initial and rate-limiting step in the synthesis of the neurotransmitter serotonin. It is also the first enzyme in the synthesis of melatonin. Tryptophan hydroxylase (TPH), tyrosine hydroxylase (TH) and

(PAH) are members of a superfamily of aromatic amino acid hydroxylases, catalyzing key steps in important metabolic pathways. Analogously to

and tyrosine hydroxylase, this enzyme uses (6R)-L-erythro-5,6,7,8-

(BH₄) and dioxygen as cofactors. In humans, the stimulation of serotonin production by administration of tryptophan has an antidepressant effect and inhibition of tryptophan hydroxylase (e.g. by p-Chlorophenylalanine) may precipitate depression. The activity of tryptophan hydroxylase (i.e. the rate at which it converts L-tryptophan into the serotonin precursor L-5-hydroxytryptophan) can be increased when it undergoes phosphorylation.

Protein Kinase A In cell biology, protein kinase A (PKA) is a family of enzymes whose activity is dependent on cellular levels of cyclic AMP (cAMP). PKA is also known as cAMP-dependent protein kinase (). PKA has several functions in the cell, including regulatio ...

, for example, can phosphorylate tryptophan hydroxylase, thus increasing its activity.

Isoforms

In humans, as well as in other mammals, there are two distinct TPH genes. In humans, these genes are located on chromosomes 11 and 12 and encode two different homologous enzymes ''

TPH1 Tryptophan hydroxylase 1 (TPH1) is an isoenzyme of tryptophan hydroxylase which in humans is encoded by the ''TPH1'' gene. TPH1 was first discovered to synthesize serotonin in 1988 and was thought that there only was a single ''TPH'' gene until ...

'' and '' TPH2'' (sequence identity 71%). *TPH1 is mostly expressed in tissues that express serotonin (a neurotransmitter) in the periphery (

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different de ...

, gut, pineal gland) but it is also expressed in the central nervous system. *On the other hand, TPH2 is exclusively expressed in

neuronal A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. No ...

cell types and is the predominant isoform in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

Additional images

Image:5htsynt 2.png , The pathway for the synthesis of serotonin from tryptophan Image:Trp-5ht-pathway.svg , Metabolic pathway from tryptophan to serotonin

References

External links

* * See als
tryptophan hydroxylase
i
Proteopedia
EC 1.14.16 {{1.14-enzyme-stub

Function

Isoforms

Additional images

See also

References

Further reading

External links