Interactions of TPH2 and TPH1 in Biosynthesis Pathways

Abstract

Tryptophan hydroxylase‐2 (TPH2) is mainly located in neurons of the raphe nuclei. A small percentage of TPH2 can also be found through neurons in the wall of the digestive tract. Tryptophan hydroxylase‐1 (TPH1) is mainly found in the pancreas. This protein's alpha‐fold structure determines the rate of the appearance in serotonin through biosynthesis pathways. Serotonin (5‐HT), is a key neurotransmitter that modulates neuropsychological processes and neural activity receptors. Mutations in TPH2 can lead to psychiatric disorders such as bipolar disorder and depression. These can be used as a therapeutic response to selective serotonin reuptake in creating a first‐generation drug for humans. TPH2 has the potential of being synthetically manipulated to create a greater appearance of itself, which could help reduce depression in patients. Other disorders positively affected by increased activation of TPH2 include schizophrenia, autism, aggression, and suicidal behavior. Studies are being done to further pave the way for the development of animal models for behavioral and pharmacological studies. Additionally, TPH1’s impact on serotonin synthesis production throughout the body will be discussed with regards to its involvement in neuropsychiatric disorders similar to TPH2. Identified 15 years prior to TPH2, TPH1 is TPH2’s peripheral counterpart. TPH1 is predominantly expressed during the late developmental stages in the brain and is synthesizing serotonin throughout the body. Although TPH1 is particularly responsible for serotonin synthesis in enterochromaffin cells, mammary glands, lungs, and the pancreas, it is also found in the brain’s pineal gland. TPH1 shows a greater affinity for tryptophan, an amino acid used in the production of serotonin, and has a stronger enzymatic activity than TPH2 for a developing brain stem. Due to the chemical and physical specificity of the blood‐barrier which distinguishes TPH2 in the brain from the rest of the body, TPH1 and TPH2 inhibitors will function differently in the brain than in the body.