Phenol Group in Pyridoxamine Acts as a Stabilizing Element for Its Carbinolamines and Schiff Bases

Abstract

Pyridoxamine (PM), a natural derivative of vitamin B(6) , possesses a high biological and biomedical significance by virtue of its acting as enzyme cofactor in amino acid metabolism and as inhibitor in the nonenzymatic glycation of proteins. Both types of processes require the initial formation of a Schiff base. In this work, we used NMR spectroscopy to study the formation mechanism for a Schiff base between PM and formaldehyde (FA). This allowed the Schiff base and an intermediate carbinolamine (CA) to be detected. The Schiff base was found to be in isomeric equilibrium with a hemiaminal (HE) form. The formation equilibrium constants for the CA and HE over the pD range of 6.0-13.0 were determined and compared with those for the reaction between 4-picolylamine (PAM) and formaldehyde (FA). The comparison revealed a strong influence of the phenol group on the equilibrium constant. Based on the results, the phenol group in PM is a key structural element towards stabilizing the resulting carbinolamine and Schiff base.

Reactivity, Selectivity, and Reaction Mechanisms of Aminoguanidine, Hydralazine, Pyridoxamine, and Carnosine as Sequestering Agents of Reactive Carbonyl Species: A Comparative Study

“…[16] Phenolic and amine groups were found to be directly engaged by condensation between PM and GO, which involves two molecules for each reactant and generates piperazine-based five-ring adduct 2.2 as already described by Voziyan et al [26] (m/z = 417.17478). Under our conditions we were unable to detect the corresponding Schiff base, although previouss tudies suggest that the condensation of carbonyl groups with the PM primary amine should be promoted by the vicinal phenolic function, which assists the formation of the carbinolamine intermediate.…”

“…[1,14] Moreover,t he direct RCS-sequestering effect has been demonstrated under in vivo conditions by identifying the corresponding reaction products in urine and serum. [16] Such chemical diversity suggestst hat the reactivity of these sequestering agentst owards the different classes of RCS should be different. In particular, CAR is ad ipeptide bearinga na mino group and an imidazole ring, whereas PM is ap henyl derivativep resenting ap rimary amino group and ap henolic functioni nvolved in the quenching mechanisms.…”

Pyridoxamine protects proteins from damage by hypohalous acids in vitro and in vivo

“…S1. Thus, PM can scavenge hypohalous acids due, in part, to high reactivity of its 4-aminomethyl group [19]. …”

Cholesterol in the retina: The best is yet to come

“…The later, indirectly confirmed in a separate study demonstrating that the isoLG modification impairs CYP27A1 activity in vitro (Charvet et al, 2013a), gave impetus to the pharmacologic treatments with pyridoxamine, former dietary supplement, now an investigational new pharmaceutical, as the FDA has changed its regulatory status in 2009. Pyridoxamine, efficient scavenger of lipid peroxidation products including isoLGs (Caldes et al, 2011), was administered to mice after they were exposed to bright light to induce the formation of isoLGs (Charvet et al, 2013b). This treatment tested whether pharmacologic targeting of the downstream steps in the oxidative injury cascade, e.g.…”