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Pyridoxamine (PM) is one of three natural forms of vitamin B6. It is a critical transient intermediate in catalysis of transamination reactions by vitamin B6-dependent enzymes. The discovery eight years ago that PM can inhibit the Maillard reaction stimulated new interest in this B6 vitamer as a prospective pharmacological agent for treatment of complications of diabetes. PM application in diabetic nephropathy has now progressed to a phase III clinical trial. Investigation of the PM mechanism of action demonstrated that PM inhibits post-Amadori steps of the Maillard reaction by sequestering catalytic metal ions and blocking oxidative degradation of Amadori intermediate. PM also has the capacity to scavenge toxic carbonyl products of sugar and lipid degradation, and to inhibit reactive oxygen species. These multiple activities position PM as a promising drug candidate for treatment of multifactorial chronic conditions in which oxidative reactions and/or carbonyl compounds confer pathogenicity.