Maillard reaction: the Amadori rearrangement template

The amine adds to the open-chain aldehyde of glucose and loses water to an iminium ion (in equilibrium with the cyclic N-glucosylamine). Loss of the C2 proton gives the 1,2-enaminol, which tautomerises to the Amadori product, the start of browning.

Mechanism step by step

A reducing sugar and an amino group form an N-glycosylamine, which rearranges to the 1-amino-1-deoxy-2-ketose

1. Addition – The amine attacks the aldehyde carbon
2. Proton transfer – A carbinolamine (hemiaminal)
3. Protonation – Acid turns the OH into a leaving group
4. Loss of water – The nitrogen lone pair pushes out water: an iminium ion (protonated Schiff base)
5. N-Glucosylamine – The C5–OH closes the ring, as in the hemiacetal; it reopens for the next step
6. Enolisation – Water removes H from C2: the 1,2-enaminol
7. Keto form – C1 is protonated as the enol O forms C=O⁺H
8. Deprotonation – The Amadori product, a 1-amino-1-deoxy-2-ketose

Key points

• Steps 1–5 are the reversible early stage; the Amadori rearrangement (6–8) is the first effectively irreversible step. Ketoses give Heyns products instead.
• Later stages (summarised): Amadori products enolise and lose the amine to reactive dicarbonyls (3-deoxyglucosone), which give furans such as HMF.
• Dicarbonyls also break down amino acids to aldehydes and CO₂ (Strecker degradation, aroma), and condense into brown nitrogenous polymers, the melanoidins.
• The same chemistry glycates proteins in the body: HbA1c is Amadori-modified haemoglobin and tracks blood glucose over weeks.

Drawn with 269 atoms, 26 arrows, 13 shapes – every one editable in MolDraw.

Sources

• Nelson & Cox, Lehninger Principles of Biochemistry, 8th ed., 2021, ch. 7 Textbook
• Berg, Tymoczko, Gatto & Stryer, Biochemistry, 9th ed., 2019 Textbook
• Hellwig & Henle, Angew. Chem. Int. Ed. 2014, 53, 10316 Review