非酶糖基化(又称美拉德反应)是还原糖和胺之间的一系列随机自发反应,导致不可逆的晚期糖基化终产物(AGE)的形成。在食品化学中,这个过程是有益的,有助于风味,香气,纹理,和熟食的外观。在体内,然而,美拉德反应是有害的,因为生物大分子的不受控制的修饰和交联损害了它们的功能。因此,糖尿病的慢性高血糖症,例如,导致非酶糖基化增加和多样化,糖尿病并发症的多器官病理学。基于有毒化合物的事实,如自由基,通过特定的防御机制在体内解毒,人们期望找到控制葡萄糖毒性的机制。到目前为止,只有一种这样的酶,果糖胺-3-激酶(FN3K),已被定性。它通过催化ATP依赖性去除Maillard加合物在细胞内运作,D-果糖赖氨酸,来自蛋白质,从而减少从葡萄糖到AGE的美拉德反应通量。当FN3K被分离时,与之紧密相关但独特的蛋白质。与FN3K不同,然而,这种酶,果糖胺-3-激酶相关蛋白(FN3KRP),不会磷酸化D-果糖赖氨酸,但会磷酸化其他几种(非生理)底物。有趣的是,FN3KRP在自然界中的分布似乎几乎是普遍的,而FN3K的分布仅限于吸热。在这篇文章中,建议FN3KRP的功能是果糖赖氨酸下游的美拉德加合物的去糖基化。这样的机制,如果证明是正确的,对于FN3KRP与某些慢性病症和/或疾病之间的明显相关性的报告将是有价值的,例如最近的出版物提出FN3KRP基因可能是长寿基因。
Non-enzymatic glycation (a.k.a. Maillard reaction) is a series of random spontaneous reactions between reducing sugars and amines, resulting in the formation of irreversible advanced glycation endproducts (AGE\'s). In food chemistry, this process is beneficial by contributing to the flavor, aroma, texture, and appearance of cooked foods. In vivo, however, Maillard reaction is deleterious because uncontrolled modification and crosslinking of biological macromolecules impairs their function. Consequently, chronic hyperglycemia of diabetes mellitus, for instance, leads to increased non-enzymatic glycation and diverse, multi-organ pathologies of diabetic complications. Based on the fact that toxic compounds, such as free radicals, are detoxified in vivo by specific defense mechanisms, one would expect to find mechanisms to control glucose toxicity as well. Thus far, only one such enzyme, fructosamine-3-kinase (FN3K), has been characterized. It operates intracellularly by catalyzing ATP-dependent removal of Maillard adducts, D-fructoselysines, from proteins, thereby reducing the Maillard reaction flux from glucose to AGE\'s. When FN3K was isolated, a closely related but distinct protein copurified with it. Unlike FN3K, however, this enzyme, fructosamine-3-kinase-related protein (FN3KRP), does not phosphorylate D-fructoselysines but it does phosphorylate several other (non-physiological) substrates. Interestingly, the distribution of FN3KRP in nature appears to be nearly universal whereas that of FN3K is limited to endotherms. In this article, it is suggested that the function of FN3KRP is
deglycation of Maillard adducts downstream from fructoselysines. Such a mechanism, if proven correct, would be valuable given reports on apparent correlations between FN3KRP and some chronic conditions and/or diseases, such as a recent publication which proposes that the FN3KRP gene may be a longevity gene.