Formation of reactive intermediates from Amadori compounds under physiological conditions.
Formation of reactive intermediates from Amadori compounds under physiological conditions.
复制标题
在生理条件下由 Amadori 化合物形成反应中间体。
DOI：
10.1006/abbi.1995.1073
复制
发表时间：
1995
影响因子：
3.9
通讯作者：
Baynes,JW
中科院分区：
文献类型：
--
作者：
Zyzak,DV;Richardson,JM;Thorpe,SR;Baynes,JW
还原糖和蛋白质之间的美拉德或布朗宁反应有助于体内组织蛋白质的化学老化和糖尿病中蛋白质的加速老化。为了鉴定生理条件下美拉德反应中形成的活性碳水化合物中间体，我们研究了Amadori模型化合物N α-甲酰-N α-果糖赖氨酸（fFL）和Amadori化合物在糖化胶原蛋白上在pH 7.4和37 ° C下的分解。由于缓冲液和氧化条件对Amadori化合物的分解有影响，本文研究了Amadori化合物在不同磷酸盐浓度和N-2-羟乙基哌嗪-N ′-2-乙磺酸（Hepes）缓冲液中有氧和厌氧条件下的分解动力学和产物。与Hepes缓冲液相比，fFL在磷酸盐中的半衰期显著较短，并且与厌氧条件相比，在有氧条件下fFL的半衰期显著较短。通过增加磷酸盐浓度和/或pH值，加速了糖化胶原蛋白上的fFL和Amadori加合物的分解。葡萄糖和甘露糖被鉴定为通过逆转Amadori重排形成的主要产物，沿着丁糖、戊糖和3-脱氧葡萄糖醛酮，通过逆转羟醛缩合、重排和水解反应形成。丁糖和戊糖产物包括醛糖和酮糖。这些相同的产品也形成了类似的产率在体外分解的Amadori加合物上的糖化胶原蛋白。Amadori化合物在体内自发分解为更具反应性的糖，包括四糖、戊糖和3-脱氧葡萄糖醛酮，提供了在生理条件下产生反应性中间体以及由于蛋白质糖基化而传播蛋白质损伤的机制体内葡萄糖。
The Maillard or browning reaction between reducing sugars and proteins contributes to the chemical aging of tissue proteins in vivo and to the accelerated aging of proteins in diabetes. To identify reactive carbohydrate intermediates formed in the Maillard reaction under physiological conditions, we studied the decomposition of the model Amadori compound, Nα-formyl-Nϵ-fructoselysine (fFL) and of Amadori compounds on glycated collagen at pH 7.4 and 37°C. Because of effects of buffer and oxidative conditions on the decomposition of Amadori compounds, the kinetics and products of decomposition were studied in varying phosphate concentrations and in N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid (Hepes) buffer under both aerobic and anaerobic conditions. The half-life of fFL was significantly shorter in phosphate, compared to Hepes buffer, and under aerobic, compared to anaerobic, conditions. The decomposition of both fFL and Amadori adducts on glycated collagen was accelerated by increasing the phosphate concentration and/or pH. Glucose and mannose were identified as major products formed by reversal of the Amadori rearrangement, along with tetroses, pentoses, and 3-deoxyglucosone, formed by reverse aldol, rearrangement, and hydrolysis reactions. The tetrose and pentose products included both aldose and ketose sugars. These same products were also formed in similar yields on decomposition of Amadori adducts on glycated collagen in vitro. The spontaneous decomposition of Amadori compounds to more reactive sugars in vivo, including tetroses, pentoses, and 3-deoxyglucosone, provides a mechanism for generating reactive intermediates under physiological conditions and for propagating damage to protein as a result of glycation of proteins by glucose in vivo.