An overview of tryptophan hydroxylase (TPH)
Tryptophan hydroxylase (TPH) is a member of aromatic amino acid hydroxylase (AAAH), and it has many subunit assembly domains. There are a large number of hydrophobic bonds and salt bridges interactions between the subunits, among which serine (Ser) is the binding sites of protein kinase A (PKA), while the C-terminal leucine zipper structure is responsible for the formation of the total enzyme in the tetramer. And the structure of TPH is conservative in all animals, and its activity is regulated by many mechanisms, such as phosphorylation after transcription, dynamic inhibition, and covalent modification. TPH also plays a very important role in the growth and development of organism and the process of behavior change.
Major types of tryptophan hydroxylase (TPH)
In recent years, it has been found that there are two subtypes of TPH gene, including TPH-1 gene and TPH-2 gene. The TPH-1 gene is mainly expressed in the outer circumference and pineal gland, and the TPH-2 gene is more active in the brain stem.
Inhibition of tryptophan hydroxylase (TPH)
4-Chloro-DL-phenylalanine is an irreversible and selective inhibitor of TPH. TPH is a speed-limiting enzyme in the synthesis of serotonin, and 4-Chloro-DL-phenylalanine can deplete endogenous serotonin levels.
Tryptophan hydroxylase (TPH) and diseases
Some patients with depression in clinical practice commit suicide while others of the same severity have no suicidal behavior, which suggests that suicide is not simply the result of repeated episodes of depression. Genetic data show that suicidal behavior has inherited susceptibility to depression which is one of the major causes of suicide, and there is a significant overlap between suicidal behavior and heredity in depression. Studies have found that mutations in intron 7, 8, 9 and 3-terminal non-coding regions were associated with attempted suicide, especially in individuals with a history of extreme suicide attempts and a history of depression. Thus, it can be concluded that the mutation of the TPH-1 gene near the 3' end could be a predisposing factor for suicidal behavior, affective disorder and pathological attack.