The inhibitory kinetics and mechanism of glycolic acid on lipase.

Obesity is prone to cause a variety of chronic metabolic diseases, and it has aroused people's attention that the rapid increase in the global population of obese people in the past years. As a kind of weight-loss drug acting in the intestine, lipase inhibitor does not enter the bloodstream without producing central nervous side effects. Because they do not affect the metabolism system, lipase inhibitors and obesity have become one of the hot spots in recent years. Glycolic acid is a new substrate analog inhibitor with the value of the semi-inhibitory concentration of lipase is estimated to be 17.29 ± 0.14 mM. Using the plots of Lineweaver-Burk, the inhibition mechanism of lipase by glycolic acid was reversible and the inhibition type belongs to competitive inhibition with a K_I value of 19.61 ± 0.26 mM. The inhibitory kinetics assay showed that the microscopic velocity constant k₊₀ of inhibition kinetics is 1.79 × 10^-3 mM^-1s^-1, and k_-0 is 0.73 × 10^-3 s^-1. The results of UV full-wavelength scanning on product cumulative, fluorescence quenching and molecular simulation also indicated that glycolic acid and substrate competitive with lipase by binding to Lys137. Thereby glycolic acid inhibiting the oxidation-catalyzed reaction and reducing the product of the enzyme and substrate. This adds a new direction for the search for lipase inhibitors and provides new ideas about the development of anti-obesity drugs. Abbreviations DMSO Dimethylsulfoxide MML Lipase from Mucor miehei PDB Protein Date Bank WHO World Health Organization 4-NPP 4-Nitrophenyl palmitate Communicated by Ramaswamy H. Sarma.