Description
THEORETICAL THERMOCHEMICAL ESTIMATIONS OF SEROTONIN FORMATION IN NEUROBIOLOGICAL PATHWAYS. Angelina Thotam, Aniyah Barnett, McKenzie Mcneill, Emmani Shaw,Ivana Thigpen, Michelle Waddell & Insu F. Hahn, Dept. of Biology and Dept. of Chemistry & Biochemistry, Hampton University. Serotonin is a key neurotransmitter that plays a critical role in mood regulation and the pathophysiology of depression. One of the most relevant approaches to studying this relationship involves the depletion of tryptophan, an amino acid precursor to serotonin. Despite this, there is minimal research on the secondary reaction in creating serotonin. The serotonin synthesis mechanism involves two enzymatic steps: the hydroxylation of tryptophan to 5-hydroxytryptophan, followed by the decarboxylation of 5-HTP to serotonin. In this computational study, the thermochemical characteristics of converting 5-hydroxytryptophan to serotonin were investigated utilizing L-amino acid decarboxylase, an enzyme, and the formation of carbon dioxide as a byproduct. Two semi-empirical quantum chemical calculation platforms were compared and used to model the tested molecules and calculate thermochemical properties (i.e., structure, stability, and reactivity) during the biosynthetic pathways of serotonin. Computational analysis revealed that the decarboxylation reaction exhibited a positive enthalpy change (ΔH>0), indicating that the process is endothermic and requires an input of energy to proceed. This finding suggests that enzymatic facilitation is critical in overcoming the energetic barrier associated with serotonin formation. The obtained data provides insight into further explaining the molecular-level behavior and energetic demands of serotonin and may contribute to a deeper understanding of pre-existing therapies targeting decreased serotonin levels in the brain. (Supported by: DOEd, R. McNair Program, Hampton Univ.).