靶标信息
Phenylalanine hydroxylase (PAH), tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) comprise a small family of monooxygenases that use tetrahydropterine as a cofactor during the catabolism of aromatic L-amino acids. PAH, TH and TPH all contain catalytic domains with an amino-terminal regulatory domain and a short carboxy-terminal tetramerization domain. Each of these enzymes also contains a single ferrous iron atom, which is bound to two histidines and a glutamate and is likely to be involved in the formation of the hydroxylating intermediate. TPH is the first and rate-limiting step in the biosynthesis of serotonin in the central nervous system and melatonin in the pineal gland. Alteration of TPH function may be a key factor in the pathology of several neuropsychiatric disorders associated with serotonin, including depression, aggression, alcoholism and schizophrenia. For instance, L-DOPA, which is used as a common therapy for Parkinson’s disease (PD) patients, inhibits TPH function, which subsequently, is thought to contribute to the onset of depression in PD patients.