Tessier Frederic J, Monnier Vincent M, Sayre Lawrence M, Kornfield Julia A
Department of Chemical Engineering, California Institute of Technology, 1200 East Colarado Blvd, Pasadena, CA 91125, USA.
Biochem J. 2003 Feb 1;369(Pt 3):705-19. doi: 10.1042/BJ20020668.
The role of the highly reactive triose sugars glyceraldehyde and glyceraldehyde-3-phosphate in protein cross-linking and other amino acid modifications during the Maillard reaction was investigated. From the incubation of glyceraldehyde with N (alpha)-acetyl-L-lysine and N (alpha)-acetyl-L-arginine, we isolated four new Maillard reaction pyridinium compounds named 'triosidines'. Two of them, 'lys-hydroxy-triosidine' [1-(5-amino-5-carboxypentyl)-3-[(5-amino-5-carboxypentylamino)methyl]-5-hydroxypyridinium] and 'arg-hydroxy-triosidine' [2-(4-amino-4-carboxybutylamino)-8-(5-amino-5-carboxypentyl)-6-hydroxy-3,4-dihydro-pyrido[2,3-d]pyrimidin-8-ium] are fluorescent, UV-active Lys-Lys and Lys-Arg cross-links respectively. Their structures were identified by NMR and MS. In addition, two UV-active lysine adducts, 'trihydroxy-triosidine' [1-(5-amino-5-carboxypentyl)-3,4-dihydroxy-5-(hydroxymethyl)pyridinium] and 'triosidine carbaldehyde' [1-(5-amino-5-carboxypentyl)-3-formylpyridinium] were tentatively identified by MS. All structures involve six sugar-derived carbons as part of the heterocyclic ring. Of the two novel cross-links, only arg-hydroxy-triosidine was formed by glyceraldehyde-3-phosphate, an intermediate metabolite of the glycolytic pathway. Lys-hydroxy-triosidine and arg-hydroxy-triosidine were detected in human and porcine corneas treated with glyceraldehyde. The HPLC-fluorescence identification was confirmed by MS. Triosidines were also formed from dihydroxyacetone, a widely used artificial sun-tanning agent. Triosidines are expected to be useful tools in tissue engineering, where the utilization of highly reactive sugars is needed to stabilize the loose matrix. In addition, they are expected to be present in selected biological conditions, such as on consumption of a high fructose diet, and syndromes associated with high glyceraldehyde excretion, such as Fanconi Syndrome, fructose-1,6-diphosphatase deficiency and tyrosinaemia.
研究了高反应性的丙糖甘油醛和3-磷酸甘油醛在美拉德反应中蛋白质交联及其他氨基酸修饰过程中的作用。通过甘油醛与N-α-乙酰-L-赖氨酸和N-α-乙酰-L-精氨酸的孵育，我们分离出了四种新的美拉德反应吡啶鎓化合物，命名为“三糖啶”。其中两种，“赖氨酸羟基三糖啶”[1-(5-氨基-5-羧基戊基)-3-[(5-氨基-5-羧基戊基氨基)甲基]-5-羟基吡啶鎓]和“精氨酸羟基三糖啶”[2-(4-氨基-4-羧基丁基氨基)-8-(5-氨基-5-羧基戊基)-6-羟基-3,4-二氢吡啶并[2,3-d]嘧啶-8-鎓]分别是荧光性、紫外线活性的赖氨酸-赖氨酸和赖氨酸-精氨酸交联物。它们的结构通过核磁共振和质谱鉴定。此外，两种紫外线活性赖氨酸加合物，“三羟基三糖啶”[1-(5-氨基-5-羧基戊基)-3,4-二羟基-5-(羟甲基)吡啶鎓]和“三糖啶甲醛”[1-(5-氨基-5-羧基戊基)-3-甲酰基吡啶鎓]通过质谱初步鉴定。所有结构都包含六个源自糖的碳原子作为杂环的一部分。在这两种新型交联物中，只有精氨酸羟基三糖啶是由糖酵解途径的中间代谢产物3-磷酸甘油醛形成的。在经甘油醛处理的人角膜和猪角膜中检测到了赖氨酸羟基三糖啶和精氨酸羟基三糖啶。通过质谱证实了高效液相色谱-荧光鉴定。三糖啶也由二羟基丙酮形成，二羟基丙酮是一种广泛使用的人工晒黑剂。三糖啶有望成为组织工程中的有用工具，在组织工程中需要利用高反应性糖来稳定疏松基质。此外，预计它们会在特定的生物学条件下出现，例如食用高果糖饮食时，以及与高甘油醛排泄相关的综合征中，如范科尼综合征、果糖-1,6-二磷酸酶缺乏症和酪氨酸血症。
