Luna Carolina, Arjona Alexis, Dueñas Carmen, Estevez Mario
Emergency unit, Hospital Nuestra Señora de la Montaña, Servicio Extremeño de Salud, Gobierno de Extremadura, 10002 Cáceres, Spain.
Family and Community Medicine, Servicio Extremeño de Salud, Gobierno de Extremadura, 10002 Cáceres, Spain.
Antioxidants (Basel). 2021 Mar 17;10(3):474. doi: 10.3390/antiox10030474.
Understanding the molecular basis of the disease is of the utmost scientific interest as it contributes to the development of targeted strategies of prevention, diagnosis, and therapy. Protein carbonylation is a typical feature of glyco-oxidative stress and takes place in health disorders such as diabetes. Allysine as well as its oxidation product, the α-amino adipic acid (α-AA) have been found to be markers of diabetes risk whereas little is known about the chemistry involved in its formation under hyperglycemic conditions. To provide insight into this issue, human serum albumin was incubated in the presence of FeCl3 (25 μM) and increasing glucose concentrations for 32 h at 37 °C. These concentrations were selected to simulate (i) physiological fasting plasma concentration (4 mM), (ii) pathological pre-diabetes fasting plasma concentration (8 mM), and pathological diabetes fasting plasma concentration (12 mM) of glucose. While both allysine and α-AA were found to increase with increasing glucose concentrations, the carboxylic acid was only detected at pathological glucose concentrations and appeared to be a more reliable indicator of glyco-oxidative stress. The underlying chemical mechanisms of lysine glycation as well as of the depletion of tryptophan and formation of fluorescent and colored advanced glycation products are discussed.
了解该疾病的分子基础具有极大的科学意义，因为它有助于制定有针对性的预防、诊断和治疗策略。蛋白质羰基化是糖氧化应激的典型特征，发生在糖尿病等健康疾病中。已发现烯赖氨酸及其氧化产物α-氨基己二酸（α-AA）是糖尿病风险的标志物，而对于高血糖条件下其形成所涉及的化学过程知之甚少。为深入了解这一问题，将人血清白蛋白在FeCl3（25 μM）存在及葡萄糖浓度不断增加的情况下于37℃孵育32小时。选择这些浓度是为了模拟（i）生理空腹血浆浓度（4 mM）、（ii）病理前期糖尿病空腹血浆浓度（8 mM）和病理糖尿病空腹血浆浓度（12 mM）的葡萄糖水平。虽然发现烯赖氨酸和α-AA均随葡萄糖浓度增加而增加，但仅在病理葡萄糖浓度下检测到羧酸，且似乎是糖氧化应激更可靠的指标。本文讨论了赖氨酸糖基化以及色氨酸消耗和荧光及有色晚期糖基化产物形成的潜在化学机制。
