TPH1

Tryptophan hydroxylase 1 (tryptophan 5-monooxygenase), also known as TPH1, is an is_associated_with::enzyme which in humans is encoded by the TPH1 is_associated_with::gene.

TPH1 was first discovered to synthesize is_associated_with::serotonin in 1988 and was thought that there only was a single TPH gene until 2003, while a second form was found in the mouse (Tph2), rat and human brain (is_associated_with::TPH2) and the original Tph/TPH was then renamed to Tph1/TPH1.

Function
Tryptophan hydroxylase (TPH; EC 1.14.16.4) catalyzes the is_associated_with::biopterin-dependent monooxygenation of is_associated_with::tryptophan to is_associated_with::5-hydroxytryptophan (5-HTP), which is subsequently decarboxylated to form the neurotransmitter is_associated_with::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, is_associated_with::pinealocytes, is_associated_with::mast cells, mononuclear is_associated_with::leukocytes, beta-cells of the islets of Langerhans, and intestinal and pancreatic is_associated_with::enterochromaffin cells.

Tph1 is not expressed in the mouse brain.

Clinical significance
is_associated_with::Tryptophan hydroxylase is important for the is_associated_with::brain. However, Tph1 is not detected in the brain. Nevertheless the effect of variations in the TPH1 is_associated_with::gene on brain-related variables, such as is_associated_with::personality traits and is_associated_with::neuropsychiatric disorders, has been studied. For example, one study (1998) found an association between a polymorphism in the gene with impulsive-is_associated_with::aggression measures, while a is_associated_with::case-control study (2001) could find no association between polymorphisms and is_associated_with::Alzheimer's Disease.

One human mutant of TPH1, A218C found in is_associated_with::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.