Challenging a mathematical model of amino acid metabolism in the small intestine, developed in pigs

A better understanding of the interplay between digestive processes and the metabolism of amino acids (AAs) in the small intestine (SI) is valuable for nutritional research. In a previous study, a conceptual model of AA fluxes in the SI was proposed. The SI was represented as a series of segments, each with the same structure and the main processes occurring for a generic AA were represented. The model considered AAs in different pools, differing in form (i.e., as free AA or as protein) and location (i.e., luminal or intestinal). Several important features of the SI, such as homeostasis and saturation of AA transporters, were explicitly implemented in the model. For simplicity reasons, certain aspects and nutritional conditions were not yet considered, including the energy cost of metabolic processes (e.g., protein synthesis and AA transport) and the catabolism of AAs (e.g., to provide energy). The initial model considered that endogenous secretions were driven by the presence of intact protein in the lumen, ignoring the presence of other substrates. These aspects were included in the revised model, while maintaining a structure based on a generic AA. The model was also challenged by varying different internal (e.g., different rates of hydrolysis between dietary and endogenous proteins) and external conditions (i.e., diet composition and meal frequency). The addition of catabolism slightly reduced export of AAs to blood and forced the SI to take up AAs from the blood during the nocturnal period. The energy cost of SI metabolism was estimated at 18 mol ATP/day (i.e., the equivalent of 105 g of glucose), most of which was driven by the cost of protein synthesis (83% of the total cost). Increasing the non-digestible fraction of the diet from 5 to 20% increased ileal endogenous losses more than endogenous secretions (i.e., 61 vs 26%). This occurred because the non-digestible fraction stimulates endogenous secretions all along the SI, including the distal parts where secretions are less prone to being hydrolysed and reabsorbed. Increasing the meal frequency increased endogenous secretions (33%), without affecting apparent ileal digestibility, due to more proximal secretions that can be hydrolysed and reabsorbed. A decrease in the rate of hydrolysis of endogenous proteins (-50%) mainly affected ileal endogenous losses (58%) and the apparent ileal digestibility (-10%). Overall, the model provided a systemic framework to integrate current knowledge and views on the complex aspects of intestinal metabolism that are difficult to address experimentally.