Luminal substrate "brake" on mucosal maltase-glucoamylase activity regulates total rate of starch digestion to glucose

BACKGROUND: Starches are the major source of dietary glucose in weaned children and adults. However, small intestine α-glucogenesis by starch digestion is poorly understood due to substrate structural and chemical complexity, as well as the multiplicity of participating enzymes. Our objective was dissection of luminal and mucosal α-glucosidase activities participating in digestion of the soluble starch product maltodextrin (MDx). PATIENTS AND METHODS: Immunoprecipitated assays were performed on biopsy specimens and isolated enterocytes with MDx substrate. RESULTS: Mucosal sucrase-isomaltase (SI) and maltase-glucoamylase (MGAM) contributed 85% of total in vitro α-glucogenesis. Recombinant human pancreatic α-amylase alone contributed <15% of in vitro α-glucogenesis; however, α-amylase strongly amplified the mucosal α-glucogenic activities by preprocessing of starch to short glucose oligomer substrates. At low glucose oligomer concentrations, MGAM was 10 times more active than SI, but at higher concentrations it experienced substrate inhibition whereas SI was not affected. The in vitro results indicated that MGAM activity is inhibited by α-amylase digested starch product "brake" and contributes only 20% of mucosal α-glucogenic activity. SI contributes most of the α-glucogenic activity at higher oligomer substrate concentrations. CONCLUSIONS: MGAM primes and SI activity sustains and constrains prandial α-glucogenesis from starch oligomers at approximately 5% of the uninhibited rate. This coupled mucosal mechanism may contribute to highly efficient glucogenesis from low-starch diets and play a role in meeting the high requirement for glucose during children's brain maturation. The brake could play a constraining role on rates of glucose production from higher-starch diets consumed by an older population at risk for degenerative metabolic disorders.