Tryptophan hydroxylase 1 (TPH1) is an
isoenzyme
In biochemistry, isozymes (also known as isoenzymes or more generally as multiple forms of enzymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. Isozymes usually have different kinetic parameters (e.g. di ...
of
tryptophan hydroxylase
Tryptophan hydroxylase (TPH) is an enzyme () involved in the synthesis of the monoamine neurotransmitter serotonin. Tyrosine hydroxylase, phenylalanine hydroxylase, and tryptophan hydroxylase together constitute the family of biopterin-depen ...
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
Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...
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
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 aromat ...
to
5-hydroxytryptophan (5-HTP), which is subsequently
decarboxylated by
aromatic amino acid decarboxylase to form the neurotransmitter
serotonin
Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...
(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
Raphe ( ; from ;Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon. revised and augmented throughout by Sir Henry Stuart Jones. with the assistance of. Roderick McKenzie.'' Oxford: Clarendon Press. : raphae or raphes) has several differe ...
neurons,
pinealocytes,
mast cell
A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a p ...
s, mononuclear
leukocyte
White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
s,
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
Tryptophan hydroxylase (TPH) is an enzyme () involved in the synthesis of the monoamine neurotransmitter serotonin. Tyrosine hydroxylase, phenylalanine hydroxylase, and tryptophan hydroxylase together constitute the family of biopterin-depen ...
is important for synthesizing
indoleamine
Indolamines are a family of neurotransmitters that share a common molecular structure. Indolamines are a classification of monoamine neurotransmitter, along with catecholamines and ethylamine derivatives. A common example of an indolamine is the ...
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
Melatonin, an indoleamine, is a natural compound produced by various organisms, including bacteria and eukaryotes. Its discovery in 1958 by Aaron B. Lerner and colleagues stemmed from the isolation of a substance from the pineal gland of cow ...
. 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 trait
In psychology, trait theory (also called dispositional theory) is an approach to the study of human personality. Trait theorists are primarily interested in the measurement of ''traits'', which can be defined as habitual patterns of behavior, thou ...
s and
neuropsychiatric disorder
A mental disorder, also referred to as a mental illness, a mental health condition, or a psychiatric disability, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. A mental disorder is ...
s, 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
*
Tryptophan hydroxylase
Tryptophan hydroxylase (TPH) is an enzyme () involved in the synthesis of the monoamine neurotransmitter serotonin. Tyrosine hydroxylase, phenylalanine hydroxylase, and tryptophan hydroxylase together constitute the family of biopterin-depen ...
*
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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EC 1.14.16