Anti-crosslinking properties of carnosine: Significance of histidine.
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Anti-crosslinking properties of carnosine: Significance of histidine.
Hobart LJ, Seibel I, Yeargans GS, Seidler NW.
Department of Biochemistry, University of Health Sciences, 1750
Independence Avenue, Kansas City, MO 64106-1453, USA.
Carnosine, a histidine-containing dipeptide, is a potential treatment
for Alzheimer's disease. There is evidence that carnosine prevents
oxidation and glycation, both of which contribute to the crosslinking
of proteins; and protein crosslinking promotes beta-amyloid plaque
formation. It was previously shown that carnosine has
anti-crosslinking activity, but it is not known which of the chemical
constituents are responsible. We tested the individual amino acids in
carnosine (beta-alanine, histidine) as well as modified forms of
histidine (alpha-acetyl-histidine, 1-methyl-histidine) and methylated
carnosine (anserine) using glycation-induced crosslinking of cytosolic
aspartate aminotransferase as our model. beta-Alanine showed
anti-crosslinking activity but less than that of carnosine, suggesting
that the beta-amino group is required in preventing protein
crosslinking. Interestingly, histidine, which has both alpha-amino and
imidazolium groups, was more effective than carnosine. Acetylation of
histidine's alpha-amino group or methylation of its imidazolium group
abolished anti-crosslinking activity. Furthermore, methylation of
carnosine's imidazolium group decreased its anti-crosslinking
activity. The results suggest that histidine is the representative
structure for an anti-crosslinking agent, containing the necessary
functional groups for optimal protection against crosslinking agents.
We propose that the imidazolium group of histidine or carnosine may
stabilize adducts formed at the primary amino group.
PMID: 15234195 [PubMed - in process]