Pathways of the Maillard reaction under physiological conditions

Abstract

Initially investigated as a color formation process in thermally treated foods, nowadays, the relevance of the Maillard reaction in vivo is generally accepted. Many chronic and age-related diseases such as diabetes, uremia, atherosclerosis, cataractogenesis and Alzheimer's disease are associated with Maillard derived advanced glycation endproducts (AGEs) and α-dicarbonyl compounds as their most important precursors in terms of reactivity and abundance. However, the situation in vivo is very challenging, because Maillard chemistry is paralleled by enzymatic reactions which can lead to both, increases and decreases in certain AGEs. In addition, mechanistic findings established under the harsh conditions of food processing might not be valid under physiological conditions. The present review critically discusses the relevant α-dicarbonyl compounds as central intermediates of AGE formation in vivo with a special focus on fragmentation pathways leading to formation of amide-AGEs.

Dicarbonyls and Advanced Glycation End-Products in the Development of Diabetic Complications and Targets for Intervention

“…This is supported by data from skin collagen which has a very long half-life where CML levels but not MG-H1 is strongly associated with donor age [56]. However, this is not true for all tissues as a strong correlation with age is seen for MG-H1 levels in lenses from normal donors [7,40]. This could be explained by a significant increase in the rate of precursor formation, namely MG, due to elevated production or an impaired detoxification mechanism.…”

“…The other major glycation pathway, which is now also classified as part of the Maillard reaction [7], proceeds via the dicarbonyls methylglyoxal (MG), glyoxal and 3-deoxyclucosone (3-DG), of which MG is the most reactive compound [23]. Dicarbonyls form via several pathways some of which are intrinsically linked with the glucose derived pathway of AGE formation.…”

“…For example CML can form via metal-catalyzed oxidative cleavage of the Amadori compound [14], polyunsaturated fatty acids [13] or ascorbic acid [12] as well as from glyoxal [15,28] (Figure 1). The mechanism of AGE formation has been summarized in an extensive review recently [7]. In diabetes, elevated levels of AGEs have mostly been attributed to enhanced precursor levels such as glucose and dicarbonyls.…”

“…In addition to proteins, the modification of DNA has also been described [5,6]. Advanced glycation end-products (AGEs) are the resulting modifications and form via a number of pathways [7,8]. The main precursors of AGEs are glucose and reactive dicarbonyls.…”

Effects of Glycosylation on the Enzymatic Activity and Mechanisms of Proteases

“…Glycosylphosphatidyl-inositol-anchored proteins (GPI-APs) are linked to glycolipids as membrane anchors, which is sometimes termed glypation [9,40]. By contrast, glycation is the uncatalyzed covalent linkage of glucose or fructose with amino groups, which is involved in diabetes and ageing related diseases [41,42]. Apart from this unregulated process, most glycans play very well defined roles in physiology, such as in the regulation of enzymatic activity.…”