Tryptophan hydroxylase 1 (TPH1) is an
isoenzyme of
tryptophan hydroxylase which in humans is encoded by the ''TPH1''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
TPH1 was first discovered to support
serotonin synthesis in 1988 by converting tryptophan into 5-hydroxytryptophan.
It was thought that there only was a single ''TPH'' gene until 2003. A second form was found in the mouse (''Tph2''), rat and human brain (
TPH2) and the original TPH was then renamed to TPH1.
Function
Tryptophan hydroxylases catalyze the
biopterin-dependent monooxygenation of
tryptophan to
5-hydroxytryptophan (5-HTP), which is subsequently
decarboxylated by
aromatic amino acid decarboxylase to form the neurotransmitter
serotonin (5-hydroxytryptamine or 5-HT). It is the rate-limiting enzyme in the biosynthesis of serotonin.
TPH expression is limited to a few specialized tissues:
raphe neurons,
pinealocytes,
mast cells, mononuclear
leukocytes,
beta-cells of the islets of Langerhans, and intestinal and pancreatic
enterochromaffin cell
Enterochromaffin (EC) cells (also known as Kulchitsky cells) are a type of enteroendocrine cell, and neuroendocrine cell. They reside alongside the epithelium lining the lumen of the digestive tract and play a crucial role in gastrointestinal r ...
s.
Clinical significance
Tryptophan hydroxylase is important for synthesizing
indoleamine neurotransmitters and related compounds in the body and
brain
The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...
, including serotonin and
melatonin. TPH1 is expressed in the body, but not the brain.
Nevertheless, the effect of variations in the TPH1
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
on brain-related variables, such as
personality traits and
neuropsychiatric disorders, has been studied.
For example, one study (1998) found an association between a
polymorphism in the gene with
impulsive-
aggression
Aggression is behavior aimed at opposing or attacking something or someone. Though often done with the intent to cause harm, some might channel it into creative and practical outlets. It may occur either reactively or without provocation. In h ...
measures,
while a
case-control study (2001) could find no association between polymorphisms and
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
.
One human mutant of TPH1, A218C found in
intron
An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e., a region inside a gene."The notion of the cistron .e., gen ...
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 is the communication of the semantics, meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The English la ...
,
transcription, or another, possibly unknown, aspect of the production of proteins from DNA.
See also
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Tryptophan hydroxylase
*
TPH2
*
Rs1799913 (A779C): intron related to figural and numeric creativity
*
rs1800532 (A218C)
References
Further reading
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External links
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