Targeted quantification of N-1-(carboxymethyl) valine and N-1-(carboxyethyl) valine peptides of β-hemoglobin for better diagnostics in diabetes.
Targeted quantification of N-1-(carboxymethyl) valine and N-1-(carboxyethyl) valine peptides of β-hemoglobin for better diagnostics in diabetes.
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DOI：
10.1186/s12014-016-9108-y
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发表时间：
2016
影响因子：
3.8
通讯作者：
Kulkarni MJ
中科院分区：
文献类型：
--
作者：
Jagadeeshaprasad MG;Batkulwar KB;Meshram NN;Tiwari S;Korwar AM;Unnikrishnan AG;Kulkarni MJ
N-1-（脱氧果糖基）缬氨酸（DFV）β-血红蛋白（β-Hb），通常称为HbA 1c，是广泛使用的糖尿病诊断标志物，被认为提供了前90-120天的血糖状态。然而，血红蛋白的周转约为120天，DFV-β-Hb是一种早期和可逆的糖基化产物，最终可能发生不可逆的晚期糖基化修饰，如羧甲基化或羧乙基化。因此，β-Hb的N-1-（羧甲基）缬氨酸（CMV）和N-1-（羧乙基）缬氨酸（CEV）肽的定量可用于评估实际血糖状态。采用高分辨-精确质谱（HR/AM）技术建立了血红蛋白合成糖基化肽段的碎片离子库。使用平行反应监测，在来自健康对照、糖尿病前期、糖尿病和控制不佳的糖尿病的临床样品中定量血红蛋白的脱氧果糖基化、羧甲基化和羧乙基化肽。本文首次报道了N-1-β-缬氨酸经羧乙基化后对β-血红蛋白的CMV和CEV多肽进行质谱定量。发现羧甲基化是N-1-β-缬氨酸的最丰富的修饰。CMV-β-Hb和CEV-β-Hb肽与空腹血糖、餐后血糖和尿微量白蛋白的相关性较好。本研究报告了羧甲基化是Hb的N-1-β-缬氨酸的主要修饰，CMV-β-Hb和CEV-β-Hb的定量可用于评估糖尿病的严重程度。本文的在线版本（doi：10.1186/s12014-016-9108-y）包含补充材料，可供授权用户使用。
N-1-(Deoxyfructosyl) valine (DFV) β-hemoglobin (β-Hb), commonly referred as HbA1c, is widely used diagnostic marker in diabetes, believed to provide glycemic status of preceding 90–120 days. However, the turnover of hemoglobin is about 120 days, the DFV-β-Hb, an early and reversible glycation product eventually may undergo irreversible advanced glycation modifications such as carboxymethylation or carboxyethylation. Hence quantification of N-1-(carboxymethyl) valine (CMV) and N-1-(carboxyethyl) valine (CEV) peptides of β-Hb would be useful in assessing actual glycemic status. Fragment ion library for synthetically glycated peptides of hemoglobin was generated by using high resolution–accurate mass spectrometry (HR/AM). Using parallel reaction monitoring, deoxyfructosylated, carboxymethylated and carboxyethylated peptides of hemoglobin were quantified in clinical samples from healthy control, pre-diabetes, diabetes and poorly controlled diabetes. For the first time, we report N-1-β-valine undergoes carboxyethylation and mass spectrometric quantification of CMV and CEV peptides of β-hemoglobin. Carboxymethylation was found to be the most abundant modification of N-1-β-valine. Both CMV-β-Hb and CEV-β-Hb peptides showed better correlation with severity of diabetes in terms of fasting glucose, postprandial glucose and microalbuminuria. This study reports carboxymethylation as a predominant modification of N-1-β-valine of Hb, and quantification of CMV-β-Hb and CEV-β-Hb could be useful parameter for assessing the severity of diabetes. The online version of this article (doi:10.1186/s12014-016-9108-y) contains supplementary material, which is available to authorized users.