New evidence for the diversity of mechanisms and protonated Schiff bases formed in the non-enzymatic covalent protein modification (NECPM) of HbA by the hydrate and aldehydic forms of acetaldehyde and glyceraldehyde

Abstract

Acetaldehyde is a physiological species existing in blood. Glyceraldehyde is a commonly-used surrogate for glucose in studies of nonenzymatic glycation. Both species exist in dynamic equilibrium between two forms, an aldehyde and a hydrate. Nonenzymatic covalent protein modification (NECPM) is a process whereby a protein is covalently modified by a non-glucose species. The purpose here was to elucidate the NECPM mechanism(s) for acetaldehyde and glyceraldehyde with human hemoglobin (HbA). For the first time, both aldehydic and hydrate forms of acetaldehyde and glyceraldehyde were considered. Computations and model reactions followed by 1 H NMR were employed. Results demonstrated that the aldehyde and hydrate forms of acetaldehyde bind and covalently-modify Val1 of HbA via different chemical mechanisms, yet generated an identical protonated Schiff base (PSB). The aldehyde and hydrate of glyceraldehyde also covalently-modified Val1 via mechanisms distinct from one another, yet generated an identical PSB.

A Bioprocessed Black Rice Bran Glutathione-Enriched Yeast Extract Protects Rats and Mice against Alcohol-Induced Hangovers

“…Modeling and analytical studies by Lewis, et al [28] suggest that a protonated Schiff base structure generated from acetaldehyde in vivo may be central to pathophysiological outcomes because it determines the structure of the stable covalent adduct formed. Also noteworthy are reports that the SH-containing amino acid L-cysteine alleviates the alcohol-related hangover symptoms of nausea, headache, stress and anxiety in humans [29].…”