Bioactive alginates and macronutrient digestion

Abstract

Macronutrient digestion is a major factor in health and metabolic diseases such as obesity and diabetes and presents a huge global challenge. Modulating macronutrient digestion with food additives and pharmaceuticals has been shown to be a fruitful approach to the treatment of obesity (Orlistat) and diabetes (Acarbose). Previous work has shown that bioactive agents have novel modulatory effects on the major enzymes of digestion, and work in this lab has shown that specific alginates can inhibit pancreatic lipase up to 70%. Alginates are now being investigated as a potential anti-obesity agent. The purpose of this thesis was to develop in vitro methodologies and an analytical approach for investigating the effects of exogenous compounds on the major digestive enzymes; -amylase, pepsin, trypsin, and lipase. A 3-step process was developed consisting of; higher-throughput single enzyme analysis, selected enzyme kinetics and model gut analysis. Alginates were shown to inhibit the action of pepsin, but have no effect on trypsin activity in vitro. The structure of alginate is key to the inhibition of pepsin, and rheological and viscometric data suggested that this effect was due to a pH dependent interaction between alginate and protein substrate as well as direct enzyme-inhibitor interactions. A similar effect was observed with Fucoidan and sulphated carrageenans. In the model gut analysis, these effects manifested as inhibition of proteolysis in the simulated gastric phase, but not in the small-intestinal phase. Alginates were shown to increase the activity of α-amylase during in vitro single enzyme analysis, but have no significant affect on carbohydrate digestion in a model gut simulation. Fat digestion in the model gut simulation was inhibited by specific alginates, adding further weight to the potential use of alginates as a therapeutic treatment of obesity.