Assessment of protein function following cross-linking by alpha-dicarbonyls.
Protein cross-linking via the Maillard reaction with alpha-dicarbonyl compounds has been the subject of intense scrutiny in the literature. We report here a study of the impact of this cross-linking on enzyme function. Protein function following glycation was examined by treating ribonuclease A with methylglyoxal, glyoxal, and diacetyl, which cross-linked the enzyme and impaired its activity. The effects of two reported Maillard reaction inhibitors, aminoguanidine and 3,5-dimethylpyrazole-1-carboxamidine, on the cross-linking reaction were assessed, with a parallel measurement of the effect on enzyme activity. The results demonstrate that preventing protein cross-linking does not necessarily preserve enzyme activity. These results cast doubt on the likely efficacy of some purported antiaging compounds in vivo.
Miller
Antonia G
AG
School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch, New Zealand.
Gerrard
Juliet A
JA
D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D003432:Cross-Linking Reagents; D004134:Dimyristoylphosphatidylcholine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D007700:Kinetics; D015416:Maillard Reaction; D011506:Proteins / Q000737:chemistry*; D011765:Pyruvaldehyde / Q000494:pharmacology*; D012259:Ribonuclease, Pancreatic / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000578:Amidines; D003432:Cross-Linking Reagents; D004791:Enzyme Inhibitors; D006146:Guanidines; D011506:Proteins; C005993:3,5-dimethylpyrazole-1-carboxamidine; D011765:Pyruvaldehyde; D012259:Ribonuclease, Pancreatic; C004479:pimagedine; D004134:Dimyristoylphosphatidylcholine