Maillard reaction of proteins

The Maillard reaction is responsible for the glycation of proteins in vivo and is believed to lie at the heart of many medical conditions, particularly diabetes and those associated with ageing, such as cataract formation, and Alzheimer's disease. It is also responsible for many changes that occur in foods during processing. Thus, the detailed study of the Maillard reaction of proteins has specific applications in both medicine and food science. Recent breakthroughs suggest that our understanding of these processes is approaching the stage where the effects of these reactions may be controlled or reversed.

One manifestation of the Maillard reaction is protein crosslinking. When two proteins are bound together covalently there is a profound effect on their structure and function. Protein aggregation explains many diabetic complications, and is also responsible for changing the functional properties of food (see below). We are trying to understand the mechanisms of protein crosslinking, in order to find ways to reverse its damaging effects and exploit its useful ones.

To date, most model studies of the Maillard reaction have employed small molecules, typically sugars and amino acids, to study the detailed mechanisms of the reaction. We are studying the reaction of proteins themselves, to gain specific information as to the nature of the reaction.

This work was supported by a Marsden grant from the Royal Society NZ.

Collaborations: Prof Jenny Ames and Prof. Harry Nursten, University of Reading, UK.

More recently we have undertaken studies ona novel class of enzymes, amadoriases, which have been shown to reverse the Maillard reaction under some conditions. Due to their relatively recent discovery, little is known about the amino acids that are involved in the catalytic mechanism and substrate binding. The elucidation of these amino acids has been a particular focus in this laboratory. Studies are also underway to resolve the crystal structures of the amadoriase enzymes.

Completed projects

Dr Antonia Miller
2000-2004 PhD thesis

Investigating the amino acid requirements of protein crosslinking, the effect of the Maillard reaction on protein function, and restoration of function by the Amadoriase enzyme.

More Details.

see:

Miller, A.G. and Gerrard, J.A. 2004: The Maillard Reaction and Food Protein Crosslinking. Invited review for the inaugural issue of Progress in Food Biopolymer Research, submitted.

Miller, A.G., Hegge, S., Uhlmann, A., Gerrard, J.A. 2004: Two time-resolved enzyme assays for functional characterisation of fructosyl amine oxidase enzymes (EC 1.5.3). Analytical Biochemistry, submitted.

Miller, A.G., Meade, S.J. and Gerrard, J.A. 2003: New insights into protein crosslinking via the Maillard reaction: structural requirements, the effect on enzyme function, and predicted efficacy of crosslinking inhibitors as anti-ageing therapeutics, Bioorganic and Medicinal Chemistry, 11: 843 – 852.

Dr Susie Meade
2000-2002 Marsden postdoctoral fellow. Studied the effects of metal ions on the Maillard reaction, exploring new methods for studying the reaction using mass spectrometry, and elucidating the mechanism of the crosslinking reaction. Currently employed as an analytical chemist at Canesis.

Meade, S.J., Miller, A.G. and Gerrard, J.A. 2003: The role of dicarbonyl compounds in non-enzymatic crosslinking: a structure-activity study, Bioorganic and Medicinal Chemistry, 11: 853 - 862.

Fayle, S.E.; Gerrard, J.A.; Simmons, L.; Meade, S.J.; Reid, E.A.; Johnston, A.C. 2000: Crosslinkage of proteins by dehydroascorbic acid and its degradation products. Food Chem, 70, 69-74.