About a year ago, I covered aspartame, the sometimes-maligned intense artificial sweetener. There is still a camp of substantial size insisting aspartame is deadly. Of course, it’s widely sold, and still FDA-approved, etc. There is one group of people for whom aspartame is undisputedly dangerous, however: phenylketonurics.
Aspartame is metabolized via esterases and peptidases – esterases remove the methyl ester as methanol (tiny, tiny quantities, but this is a big part of why some people insist this is a dangerous sweetener). This yields a dipeptide of aspartic acid and phenylalanine. Peptidases cleave the molecule into separate aspartic acid and phenylalanine molecules. The phenylalanine is what’s dangerous to phenylketonurics, who can’t metabolize it and must eat a phenylalanine-limited diet (some suggest that free aspartic acid is a dangerous metabolite of the molecule, but that’s another story). So here’s how aspartame metabolism goes:
Enter neotame, the exact same molecule with a bulky side chain on the terminal nitrogen of the aspartic acid.
The bulky carbon tail doesn’t impair the removal of the methyl ester, but it does keep it from being metabolized past the dipeptide! No phenylalanine metabolite: