Water-soluble vitamins for controlling starch digestion: Conformational scrambling and inhibition mechanism of human pancreatic α-amylase by ascorbic acid and folic acid

The inhibition of human pancreatic α-amylase (HPA) enzyme activity can offers facile routes to ameliorate postprandial hyperglycemia in diabetes via control of starch digestion. The present study utilizes complementary experimental (starch digestion kinetics, fluorescence quenching, Förster resonance energy transfer, and X-ray diffraction) and computational (molecular docking and dynamics simulation) methods to evaluate for the first time the HPA inhibitory activity of eight water-soluble vitamins. In particular, ascorbic acid inhibited HPA activity via non-competitive antagonism from two allosteric sites, by channeling the inhibition towards the active site cavity via the triose-phosphate isomerase (TIM) barrel. Whereas folic acid inhibited HPA activity by binding competitively at the active site cavity and decreasing the disorder in the neighboring loop 3 and 7, the latter are important mobile loops in HPA for starch digestion. The infusion of such biocompatible and nutritional water-soluble vitamins alongside starch may enable avenues in diabetes management.