Szwergold B S, Howell S, Beisswenger P J
Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
Diabetes. 2001 Sep;50(9):2139-47. doi: 10.2337/diabetes.50.9.2139.
Nonenzymatic glycation appears to be an important factor in the pathogenesis of diabetic complications. Key early intermediates in this process are fructosamines, such as protein-bound fructoselysines. In this report, we describe the purification and characterization of a mammalian fructosamine-3-kinase (FN3K), which phosphorylates fructoselysine (FL) residues on glycated proteins, to FL-3-phosphate (FL3P). This phosphorylation destabilizes the FL adduct and leads to its spontaneous decomposition, thereby reversing the nonenzymatic glycation process at an early stage. FN3K was purified to homogeneity from human erythrocytes and sequenced by means of electrospray tandem mass spectrometry. The protein thus identified is a 35-kDa monomer that appears to be expressed in all mammalian tissues. It has no significant homology to other known proteins and appears to be encoded by genomic sequences located on human chromosomes 1 and 17. The lability of FL3P, the high affinity of FN3K for FL, and the wide distribution of FN3K suggest that the function of this enzyme is deglycation of nonenzymatically glycated proteins. Because the condensation of glucose and lysine residues is an ubiquitous and unavoidable process in homeothermic organisms, a deglycation system mediated by FN3K may be an important factor in protecting cells from the deleterious effects of nonenzymatic glycation. Our sequence data of FN3K are in excellent agreement with a recent report on this enzyme by Delpierre et al. (Diabetes 49:1627-1634, 2000).
非酶糖基化似乎是糖尿病并发症发病机制中的一个重要因素。这一过程中的关键早期中间体是果糖胺，如与蛋白质结合的果糖赖氨酸。在本报告中，我们描述了一种哺乳动物果糖胺-3-激酶（FN3K）的纯化及特性，该激酶可将糖化蛋白上的果糖赖氨酸（FL）残基磷酸化为3-磷酸果糖赖氨酸（FL3P）。这种磷酸化作用使FL加合物不稳定并导致其自发分解，从而在早期阶段逆转非酶糖基化过程。FN3K从人红细胞中纯化至同质，并通过电喷雾串联质谱法进行测序。鉴定出的该蛋白质是一种35 kDa的单体，似乎在所有哺乳动物组织中均有表达。它与其他已知蛋白质无显著同源性，似乎由位于人类1号和17号染色体上的基因组序列编码。FL3P的不稳定性、FN3K对FL的高亲和力以及FN3K的广泛分布表明，这种酶的功能是使非酶糖基化蛋白质去糖基化。由于葡萄糖和赖氨酸残基的缩合在恒温生物中是一个普遍且不可避免的过程，由FN3K介导的去糖基化系统可能是保护细胞免受非酶糖基化有害影响的一个重要因素。我们关于FN3K的序列数据与Delpierre等人最近关于该酶的报告（《糖尿病》49:1627 - 1634, 2000）高度一致。
