Inhibition of Lipase by Orlistat: Kinetics Combined with In Silico Approaches to Visualize Interactions

Abstract

The inhibition of porcine pancreatic lipase by the drug orlistat was studied through a series of activities that combine experimental and computational procedures. The enzymatic activity of the lipase was determined by measuring enzyme kinetics and calculating parameters such as K m and V max from experimental data. Assays of lipase inhibition by orlistat were used to construct Linewaver−Burk and Dixon plots. Docking calculations are highly recommended to visualize the enzyme−ligand interactions and as an approach to decipher the inhibitor mechanism of action. Furthermore, sequence analysis was included to compare enzyme structures across different organisms, specifically between human and pig as closely related study models, and complement the docking simulations. The educational project proposed here for biochemistry or pharmacy students can enhance the understanding of concepts regarding enzyme kinetics, binding sites, and enzyme−ligand interactions through visualizations.

Inhibition of Pancreatic Lipase by Flavonoid Derivatives: In Vitro and In Silico Investigations

“…Similar competitive inhibitory characteristics against pancreatic lipase are observed in certain other flavonoid compounds, consistent with the behavior exhibited by F01 [ 35 – 37 ]. Notably, orlistat, as depicted in Figure 3(b) , also manifested competitive inhibition against the pancreatic lipase enzyme, aligning with previously reported findings on the inhibitory properties of this compound [ 38 ].…”

Panorama das publicações científicas (2019-2023) sobre Inflamação Gastrointestinal associada à Orlistate: Uma revisão integrativa da literatura

“…Esta dose é geralmente considerada um equilíbrio ideal entre eficácia e tolerabilidade. Entretanto, há uma variação significativa na resposta individual, o que pode afetar a incidência de inflamação gastrointestinal (Candela et al 2021) (Murshed et al, 2022).…”

Current Role and Potential of Polymeric Biomaterials in Clinical Obesity Treatment

“…Current medication achieves weight loss via multiple routes of mechanism. To be more specific, orlistat binds to gastric and pancreatic lipase to inhibit lipid absorption; phentermine-topiramate and naltrexone-bupropion suppress appetite via neuropathic mechanisms; while liraglutide and semaglutide act as GLP-1 receptor agonists. − According to a network meta-analysis published in the Lancet, antiobesity drugs exhibited body weight loss of 1.88% to up to 11.41%, with the interpretation that phentermine-topiramate and GLP-1 receptor agonists proved the best drugs in reducing weight when taking into account adverse effects …”