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.
PCM-TD-DFT computations were used to examine the electronic transitions exhibited by the molecular species of 2-hydroxybenzylamine (2-BNZ). The theoretical results thus obtained were found to accurately fit their experimental counterparts and to afford the assignation of the different experimental electronic transitions to 2-BNZ tautomers present in the solution. Also, the HCTH functional was found to accurately reproduce electronic excitations in the cationic species and neutral tautomer, and the B3LYP functional to provide accurate predictions of the transitions for the anionic species and zwitterionic tautomer.
Pyridoxal 5'-phosphate (PLP) is a B(6) vitamer acting as an enzyme cofactor in various reactions of aminoacid metabolism and inhibiting glycation of biomolecules. Nonenzymatic glycation of aminophospholipids alters the stability of lipid bilayers and cell function as a result. Similarly to protein glycation, aminophospholipid glycation initially involves the formation of a Schiff base. In this work, we studied the formation of Schiff bases between PLP and two compounds mimicking the polar head of natural aminophospholipids, namely: O-phosphorylethanolamine and O-phospho-D,L-serine. Based on the results, the pH-dependence of the microscopic constants of the two PLP-aminophosphate systems studied is identical with that for PLP-aminoacid systems. However, the rate and equilibrium formation constants for the Schiff bases of the aminophosphates are low relative to those for the aminoacids. A theoretical study by density functional theory of the formation mechanism for the Schiff bases of PLP with the two aminophospholipid analogues confirmed that the activation energy of formation of the Schiff bases is greater with aminophosphates; on the other hand, that of hydrolysis is essentially similar with aminoacids and aminophosphates.
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