Intestinal hydrolysis of aspartylphenylalanine--the metabolic product of aspartame.

Aspartame [Nutrasweet, Equal (Searle Consumer Products, Chicago, Ill.)] is the methyl ester of the dipeptide aspartylphenylalanine (Asp-Phe). After hydrolysis of the ester bond in the intestinal lumen, the dipeptide is apparently absorbed and digested in the same manner as dipeptides derived from protein digestion. We observed that Asp-Phe is hydrolyzed approximately equally well by three previously reported brush border dipeptidases. However, these enzymes have very low affinity for Asp-Phe, and a substantial amount of the dipeptide may be transported intact and hydrolyzed in the cytosol. Starch gel electrophoresis and ion-exchange chromatography of the cytosol of intestinal mucosa and of red blood cell lysate revealed only one peak with Asp-Phe hydrolase activity. This activity was distinct from the seven cytosolic peptidases that have been described previously. The reduction in Asp-Phe hydrolase activity in the brush border and cytosol of diseased intestinal mucosa was similar to the reduction in levels of other brush border and cytosol enzyme activities. If double-blind studies confirm that some people have symptoms caused by aspartame ingestion, it would be appropriate to test such individuals for deficiency of cytosolic Asp-Phe hydrolase activity.