Carnosine protects proteins against methylglyoxal-mediated modifications.
Methylglyoxal (MG) (pyruvaldehyde) is an endogenous metabolite which is present in increased concentrations in diabetics and implicated in formation of advanced glycosylation end-products (AGEs) and secondary diabetic complications. Carnosine (beta-alanyl-L-histidine) is normally present in long-lived tissues at concentrations up to 20 mM in humans. Previous studies showed that carnosine can protect proteins against aldehyde-containing cross-linking agents such as aldose and ketose hexose and triose sugars, and malon-dialdehyde, the lipid peroxidation product. Here we examine whether carnosine can protect protein exposed to MG. Our results show that carnosine readily reacts with MG thereby inhibiting MG-mediated protein modification as revealed electrophoretically. We also investigated whether carnosine could intervene when proteins were exposed to an MG-induced AGE (i.e. lysine incubated with MG). Our results show that carnosine can inhibit protein modification induced by a lysine-MG-AGE; this suggests a second intervention site for carnosine and emphasizes its potential as a possible non-toxic modulator of diabetic complications.
Hipkiss
A R
AR
Molecular Biology and Biophysics Group, King's College London, United Kingdom. alan.hipkiss@kcl.ac.uk
Chana
H
H
D002336:Carnosine / Q000737:chemistry / Q000494:pharmacology*; D003459:Crystallins / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D017127:Glycation End Products, Advanced / Q000737:chemistry / Q000494:pharmacology; D008239:Lysine / Q000737:chemistry / Q000494:pharmacology; D010047:Ovalbumin / Q000737:chemistry*; D011765:Pyruvaldehyde / Q000037:antagonists & inhibitors* / Q000737:chemistry
D003459:Crystallins; D017127:Glycation End Products, Advanced; D011765:Pyruvaldehyde; D002336:Carnosine; D010047:Ovalbumin; D008239:Lysine