Ironjustic
Sat, Jun-24-06, 17:15
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.
--------------------------------------------------------------
--------------
<<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]
--------------------------------------------------------------
--------------
Who loves ya. Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING http://tinyurl.com/zk9fk
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.
--------------------------------------------------------------
--------------
<<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]
--------------------------------------------------------------
--------------
Who loves ya. Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING http://tinyurl.com/zk9fk