Advanced glycation end-products / sequestration of metal

ironjustice@aol.com · medicine forum Guru Joined: 28 Apr 2005 Posts: 1522

Inhibitors of the Maillard reaction and AGE breakers as therapeutics
for multiple diseases.
Reddy VP, Beyaz A
Drug Discov Today. 2006 Jul ; 11(13-14): 646-54

The Maillard reaction is a complex series of reactions that involve
reducing-sugars and proteins, giving a multitude of end-products that
are known as advanced glycation end-products (AGEs). AGEs can
contribute to the pathogenesis of diabetes and neurological diseases
such as Alzheimer's disease. AGEs also play a major role in vascular
stiffening, atherosclerosis, osteoarthritis, inflammatory arthritis and
cataracts. Thus, AGE inhibitors and AGE breakers offer a potential
strategy as therapeutics for diverse diseases. Various AGE inhibitors
have been developed in recent years, and their underlying mechanism is
based on the attenuation of glycoxidation and/or oxidative stress by
the sequestration of metal ions, reactive 1,2-dicarbonyl compounds, and
reactive oxygen and reactive nitrogen species.

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<<snip>>
Protein molecular weight analyses support the conclusion that Amadori
decomposition pathways are constrained in the presence of metal ion
chelators and radical traps.
<<snip>>

J Biol Chem. 2003 Oct 3;278(40):38384-94. Epub 2003 Jul 23. Related
Articles, Links

Paradoxical impact of antioxidants on post-Amadori glycoxidation:
Counterintuitive increase in the yields of pentosidine and
Nepsilon-carboxymethyllysine using a novel multifunctional pyridoxamine

derivative.

Culbertson SM, Vassilenko EI, Morrison LD, Ingold KU.

Steacie Institute for Molecular Sciences, National Research Council of
Canada, Ottawa, Ontario. sean.culbert...@nrc.ca

The inhibition of post-Amadori advanced glycation end product (AGE)
formation by three different classes of AGE inhibitors, carbonyl group
traps, chelators, and radical-trapping antioxidants, challenge the
current paradigms that: 1) AGE inhibitors will not increase the
formation of any AGE product, 2) transition metal ions are required for

oxidative formation of AGE, and 3) screening AGE inhibitors only in
systems containing transition metal ions represents a valid estimate of

potential in vivo mechanisms. This work also introduces a novel
multifunctional AGE inhibitor, 6-dimethylaminopyridoxamine (dmaPM),
designed to function as a combined carbonyl trap, metal ion chelator,
and radical-trapping antioxidant. Other AGE inhibitors including
pyridoxamine, aminoguanidine, o-phenylenediamine, dipyridoxylamine, and

diethylenetriaminepentaacetic acid were also examined. The results
during uninterrupted and interrupted ribose glycations show: 1) an
unexpected increase in the yield of pentosidine in the presence of
radical-trapping phenolic antioxidants such as Trolox and dmaPM, 2)
significant formation of Nepsilon-carboxymethyllysine (CML) in the
presence of strong chelators and phenolic antioxidants, which implies
that there must be nonradical routes to CML, 3) prevention of
intermolecular cross-links with radical-trapping inhibitors, and 4)
that dmaPM shows excellent inhibition of AGE. Glucose glycations reveal

the expected inhibition of pentosidine and CML with all compounds
tested, but in a buffer free of trace metal ions the yield of CML in
the presence of radical-trapping antioxidants was between the metal
ion-free and metal ion-containing controls. Protein molecular weight
analyses support the conclusion that Amadori decomposition pathways are

constrained in the presence of metal ion chelators and radical traps.

PMID: 12878609 [PubMed - indexed for MEDLINE]

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outsor@citynet.net · medicine forum Guru Joined: 11 Sep 2005 Posts: 569

Use of aspirin, thiamine, niacin among other things helps with glycation.
For a diabetic keeping tight glucose control is the best prevention.
Metals are not the cause of this, it is excessive glucose for extended
periods sticking to proteins that is the cause so glucose control is
really one's prine concern. The a1c test measures the glycation of a
protein in blood cells.

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