TPH1
Encyclopedia
Tryptophan hydroxylase 1 (tryptophan 5-monooxygenase), also known as TPH1, is an enzyme
which in humans is encoded by the TPH1 gene
.
Until 2003 it was thought that there only was a single TPH gene, but then
a second form was found in the mouse (Tph2), rat and human brain (TPH2
) and the original Tph/TPH was then renamed to Tph1/TPH1.
-dependent monooxygenation of tryptophan
to 5-hydroxytryptophan
(5HT), which is subsequently decarboxylated
to form the neurotransmitter serotonin
. It is thus the rate-limiting enzyme in the biosynthesis of serotonin.
TPH expression is limited to a few specialized tissues: raphe
neurons, pinealocyte
s, mast cell
s, mononuclear leukocytes, beta-cells
of the islets of Langerhans, and intestinal and pancreatic enterochromaffin cells.
Tph1 is not expressed in the mouse brain.
is important for the brain
.
However, Tph1 is not detected in the brain.
Nevertheless the effect of variations in the TPH1 gene
on brain-related variables, such as personality traits and neuropsychiatric disorders, has been studied.
For example, one study found an association between a polymorphism
in the gene with impulsive
-aggression
measures,
while a case-control
study could find no association between polymorphisms and Alzheimer's Disease
.
One human mutant of TPH1, A218C found in intron
7, is highly associated with schizophrenia. Introns are regions of DNA that do not code for the amino acid sequence of a protein and were long considered to be 'junk DNA' lacking purpose. The correlation of an intron mutation with schizophrenia is significant because it suggests that introns have an important role in translation
, transcription
, or another, possibly unknown, aspect of the production of proteins from DNA.
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...
which in humans is encoded by the TPH1 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...
.
Until 2003 it was thought that there only was a single TPH gene, but then
a second form was found in the mouse (Tph2), rat and human brain (TPH2
TPH2
The enzyme Tryptophan hydroxylase 2, also known as TPH2, is an isozyme of Tryptophan hydroxylase found in vertebrates. In humans TPH2 is primarily expressed in the serotonergic neurons of the brain, with the highest expression in the raphe nucleus of the midbrain...
) and the original Tph/TPH was then renamed to Tph1/TPH1.
Function
Tryptophan hydroxylase (TPH; EC 1.14.16.4) catalyzes the biopterinBiopterin
Biopterin is a coenzyme that is produced within the body.It is an oxidized degradation product of tetrahydrobiopterin.Defects in biopterin synthesis or regeneration can cause a form of hyperphenylalaninemia ....
-dependent monooxygenation of tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...
to 5-hydroxytryptophan
5-Hydroxytryptophan
5-Hydroxytryptophan , also known as oxitriptan , is a naturally occurring amino acid and chemical precursor as well as metabolic intermediate in the biosynthesis of the neurotransmitters serotonin and melatonin from tryptophan....
(5HT), which is subsequently decarboxylated
Decarboxylation
Decarboxylation is a chemical reaction that releases carbon dioxide . Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is the first chemical step in photosynthesis, is called carbonation, the addition of CO2 to...
to form the neurotransmitter serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
. It is thus the rate-limiting enzyme in the biosynthesis of serotonin.
TPH expression is limited to a few specialized tissues: raphe
Raphe nuclei
The raphe nuclei are a moderate-size cluster of nuclei found in the brain stem. Their main function is to release serotonin to the rest of the brain...
neurons, pinealocyte
Pinealocyte
Pinealocytes are the main cells of the pineal gland. They produce and secrete melatonin. Pinealocytes have an organelle called the synaptic ribbon; this is considered to be a specific marker for pinealocytes...
s, mast cell
Mast cell
A mast cell is a resident cell of several types of tissues and contains many granules rich in histamine and heparin...
s, mononuclear leukocytes, beta-cells
Beta cell
Beta cells are a type of cell in the pancreas located in the so-called islets of Langerhans. They make up 65-80% of the cells in the islets.-Function:...
of the islets of Langerhans, and intestinal and pancreatic enterochromaffin cells.
Tph1 is not expressed in the mouse brain.
Clinical significance
Tryptophan hydroxylaseTryptophan hydroxylase
Tryptophan hydroxylase is an enzyme involved in the synthesis of the neurotransmitter serotonin. TPH catalyzes the following chemical reactionIt employs one cofactor, iron.- Function :...
is important for the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
.
However, Tph1 is not detected in the brain.
Nevertheless the effect of variations in the TPH1 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...
on brain-related variables, such as personality traits and neuropsychiatric disorders, has been studied.
For example, one study found an association between a polymorphism
Polymorphism (biology)
Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...
in the gene with impulsive
Impulsive
Impulsive may refer to:*Impulsive *Impulsivity*Impulsion*Impulse function...
-aggression
Aggression
In psychology, as well as other social and behavioral sciences, aggression refers to behavior between members of the same species that is intended to cause humiliation, pain, or harm. Ferguson and Beaver defined aggressive behavior as "Behavior which is intended to increase the social dominance of...
measures,
while a case-control
Case-control
A case-control study is a type of study design in epidemiology. Case-control studies are used to identify factors that may contribute to a medical condition by comparing subjects who have that condition with patients who do not have the condition but are otherwise similar .Case-control studies are...
study could find no association between polymorphisms and Alzheimer's Disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
.
One human mutant of TPH1, A218C found in intron
Intron
An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...
7, is highly associated with schizophrenia. Introns are regions of DNA that do not code for the amino acid sequence of a protein and were long considered to be 'junk DNA' lacking purpose. The correlation of an intron mutation with schizophrenia is significant because it suggests that introns have an important role in translation
Translation (genetics)
In molecular biology and genetics, translation is the third stage of protein biosynthesis . In translation, messenger RNA produced by transcription is decoded by the ribosome to produce a specific amino acid chain, or polypeptide, that will later fold into an active protein...
, transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
, or another, possibly unknown, aspect of the production of proteins from DNA.