Pyridoxamine / treatment of complications of diabetes

[Ironjustic]

Cell Mol Life Sci. 2005 May 18; [Epub ahead of print] Related
Articles, Links

Pyridoxamine as a multifunctional pharmaceutical: targeting
pathogenic glycation and oxidative damage.

Voziyan PA, Hudson BG.

Division of Nephrology, Vanderbilt University Medical Center,
3223 MCN, 1161 21st Avenue South, Nashville, Tennessee,
37232-2372, USA, paul.voziyan@vanderbilt.edu.

The discovery that pyridoxamine (PM) can inhibit glycation
reactions and the formation of advanced glycation end products
(AGEs) stimulated new interest in this B(6) vitamer as a
prospective pharmacological agent for treatment of
complications of diabetes. The mechanism of action of PM
includes: (i) inhibition of AGE formation by blocking
oxidative degradation of the Amadori intermediate of the
Maillard reaction; (ii) scavenging of toxic carbonyl products
of glucose and lipid degradation; and (iii) trapping of
reactive oxygen species. The combination of these multiple
activities along with PM safety posture it as a promising drug
candidate for treatment of diabetic complications as well as
other multifactorial chronic conditions in which oxidative
reactions and carbonyl compounds confer pathogenicity.

PMID: 15905958 [PubMed - as supplied by publisher]

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[Alf Christ]

On 24 May 2005 19:06:37 -0700, "ironjustice@aol.com"
<ironjustice@aol.com> wrote:

>The discovery that pyridoxamine (PM) can inhibit glycation
>reactions and the formation of advanced glycation end
>products (AGEs) stimulated new interest in this B(6) vitamer
>as a prospective pharmacological agent for treatment of
>complications of diabetes. The mechanism of action of PM
>includes: (i) inhibition of AGE formation by blocking
>oxidative degradation of the Amadori intermediate of the
>Maillard reaction; (ii) scavenging of toxic carbonyl products
>of glucose and lipid degradation; and (iii) trapping of
>reactive oxygen species. The combination of these multiple
>activities along with PM safety posture it as a promising
>drug candidate for treatment of diabetic complications as
>well as other multifactorial chronic conditions in which
>oxidative reactions and carbonyl compounds confer
>pathogenicity.

One important Amadori scavenger is taurine and hypotaurine,
whose formation in liver deeply depends on B6 status. Both
cysteine formation from homocysteine and taurine synthesis
from cysteine has B6 depended steps.

Taurine has long been known to compete with lysine for the
first Amadori step in AGE formation.