Glucose Schiffs base formation

Figure 1.37 A reducing sugar may modify protein amine groups through Schiff base formation followed by an Amadori rearrangement to give a stable ketoamine product. Glucose is a common in vivo modifier of blood proteins through this process.

Lactose is a disaccharide comprised of glucose and galactose units. These reducing sugars are reported to be present in spray dried lactose, as is the hexose degradent 5-hydroxymethyl furfural.This aldehyde has the potential for additional reactions with primary amino groups, Schiff Base formation and color development (Fig. 

As is tile case for other aldehydes, acetaldehyde can condense with amino groups to form a Schiff base. Schiff base formation occurs in a number of pathological conditions. For example, breakdown of polyunsaturated fatty adds may generate malondialdehyde, which reacts with proteins to produce damage. To review another example, the elevated plasma glucose levels in diabetes results in an increased condensation of glucose, via a Schiff base, with various proteins in the bloodstream. Aldehyde damage to proteins has been reviewed by Stadtman (1990). 

Thus, glycoproteins such as horseradish peroxidase, glucose oxidase, or most antibody molecules can be activated for conjugation by brief treatment with periodate. Cross-linking with an amine-containing protein takes place under alkaline pH conditions through the formation of Schiff base intermediates. These relatively labile intermediates can be stabilized by reduction to a secondary amine linkage with sodium cyanoborohydride (Fig. 303). 

In a kinetic study of the reaction of various amino acids with aldoses, Haugaard, Tumerman, and Silvestri108 applied a new method (see Section VIII) for following the course of the reaction. With D-glucose and DL-leucine as reactants (and an initial pH of 9.2), the reaction constants for the formation of the Schiff base at the three temperatures studied were as follows ... 

The Amadori product from D-glucose 33 and L-proline decomposes at 130 °C in DMF to afford 33 and D-Mannose 54, indicating the reversibility of the Amadori reaction. A kinetic study using 33 and phenylalanine indicates that the Schiff s base formation is the rate-determining step of the Maillard reaction [275,276]. 

Hb A with pyruvic acid attached to the N-terminal of the P-chain Hb A with glucose attached to the N-terminal valine of the P-chain Unstable Schiff base (aldimine) a labile intermediary component in the formation ofHbAic. 

---