Schiff bases protein-formaldehyde reactions

Formaldehyde reacts with proteins to form adducts and cross-links.31516 Metz et al.3 have identified three types of chemical modifications after treatment of proteins with formaldehyde (a) methylol (hydroxymethyl) adducts, (b) Schiff bases, and (c) methylene bridges. The reaction of formaldehyde with proteins is summarized in Figure 19.1, but briefly, formaldehyde reacts primarily with lysine and cysteine to form methylol adducts. The methylol adduct can subsequently undergo a dehydration reaction to form a Schiff base. Adducted primary amine and thiol groups can undergo a second reaction with arginine,... 

Figure 19.1 A schematic view of the common formaldehyde-induced modifications in proteins. Reactive methylol adducts are formed in the initial reaction between formaldehyde and cysteine or the amino groups of basic amino acid residues. The methylol adduct can subsequently undergo a dehydration reaction to form a Schiff s base. Adducted residues can undergo a second reaction to form methylene bridges or can convert to the ethoxymethyl adduct after the ethanol dehydration step.

The process of toxin inactivation by formaldehyde treatment is pooriy understood. However, it does involve the formation of a Schiff s base, either with lysine or arginine residues in the protein, foiiowed by cross-linking to residues such as tyrosine, lysine and tryptophan. The quality control for this reaction is bioassay of the resultant toxoid using an animal model but there is the possibility of using mass spectrometry to follow the modification (Fig. 27.21). ... 

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