Formation of Pent-4-en-1-amine, the Counterpart of Acrylamide from Lysine and Its Conversion into Piperidine in Lysine/Glucose Reaction Mixtures

Abstract

Isotope labeling studies performed using lysine/glucose model systems have indicated that lysine can generate piperidine, a reactive amine capable of undergoing Maillard type interactions. Two possible mechanisms were identified for the formation of piperidine: one arising through decarboxylation of lysine alone to generate cadaverine (1,5-diaminopentane) followed by deamination to form pent-4-en-1-amine which in turn can cyclize into piperidine where both Nepsilon and Nalpha atoms of lysine can be equally involved in its generation due to the symmetrical nature of the precursor diamine. On the other hand, in the presence of sugars, lysine, similarly to asparagine and phenylalanine, can undergo carbonyl-assisted decarboxylative deamination reaction to generate pent-4-en-1-amine, the counterpart of acrylamide. The pent-4-en-1-amine can then cyclize to form piperidine through the Nepsilon atom of lysine. To confirm the formation of pent-4-en-1-amine in the lysine/glucose model system, a useful strategy based on Py-GC/MS analysis was developed using isotope labeling technique to identify sugar adducts of pent-4-en-1-amine. Products simultaneously possessing five lysine carbon atoms (C2'-C6') and the Nepsilon-amino group from lysine in addition to glucose carbon atoms were targeted using specifically labeled precursors such as [(15)Nalpha]lysine.2HCl, [(15)Nepsilon]lysine.2HCl, [U-(13)C(6)]lysine.2HCl, [(13)C-6]lysine.2HCl and [U-(13)C(6)]glucose. The complete labeling studies along with structural analysis using synthetic and other available precursors have shown the presence of a peak that satisfies the above criteria, and the peak was tentatively identified as N-(5-methylfuran-2-yl)methylidene]penta-1,3-dien-1-amine incorporating pent-4-en-1-amine in its structure.