According to data from the World Health Organization, as of 2016, more than 1.9 billion adults aged 18 and over were overweight, while more than 650 million were obese. This means that approximately 13% of the world's adult population is obese. The prevalence of obesity worldwide has nearly tripled since 1975. While the total obesity rate in our country is 17%, it is reported that 20.9 percent of women and 13.7 percent of men are obese. It is known that obesity, which has the most important place in health expenditures along with the diseases it causes, is closely related to many chronic diseases.
When it comes to treating obesity, there are many treatment methods that focus on weight loss. Controlling energy intake and output is the most effective way to treat obesity. One of the most commonly used drugs in the treatment of obesity and type 2 diabetes is Orlistat. Orlistat is an inhibitor of pancreatic lipase, but it causes many side effects in patients, including soft stools. Its effectiveness also varies depending on the patient and diet. On the other hand, another active substance that could be an alternative to this drug has not yet been identified.
In this project, we aimed to test the potential of tyramine amine, which is produced from tyrosine and is a natural part of metabolism, to have an alternative effect to orlistat. Thus, the aim is to find a drug raw material that can be applied to obesity patients with more limited side effects or to have it designed through further studies. In the experimental phase, different concentrations of tyramine will be applied to the pure porcine pancreatic lipase enzyme, which is used in the literature as a model organism for humans, and its effect on the enzyme activity will be measured. Using the calculated specific activity values, the inhibition model will be revealed using the SigmaPlot 13th Enzyme Module software. In the final stage, molecular docking analysis was performed with AutoDockTools-1.5.6, Chimera 1.14, UCSF ChimeraX-1.6.1, CBDock2 and similar open source software to determine where tyramine binds on the lipase enzyme and what types of bonds and interactions it establishes with which amino acids during the binding phase. will be done. In this way, the existence, model and mechanism of inhibition will be reported as a whole, providing preliminary data for further studies. Additionally, the same experimental steps will be carried out for Orlistat to make a realistic comparison of the existing drug and tyramine under the same laboratory conditions.
