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Targeted quantification of N-1-(carboxymethyl) valine and N-1-(carboxyethyl) valine peptides of ?-hemoglobin for better diagnostics in diabetes.

ABSTRACT: BACKGROUND:N-1-(Deoxyfructosyl) valine (DFV) ?-hemoglobin (?-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-?-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 ?-Hb would be useful in assessing actual glycemic status. RESULTS: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-?-valine undergoes carboxyethylation and mass spectrometric quantification of CMV and CEV peptides of ?-hemoglobin. Carboxymethylation was found to be the most abundant modification of N-1-?-valine. Both CMV-?-Hb and CEV-?-Hb peptides showed better correlation with severity of diabetes in terms of fasting glucose, postprandial glucose and microalbuminuria. CONCLUSIONS:This study reports carboxymethylation as a predominant modification of N-1-?-valine of Hb, and quantification of CMV-?-Hb and CEV-?-Hb could be useful parameter for assessing the severity of diabetes.

SUBMITTER: Jagadeeshaprasad MG

PROVIDER: S-EPMC4812615 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Targeted quantification of N-1-(carboxymethyl) valine and N-1-(carboxyethyl) valine peptides of β-hemoglobin for better diagnostics in diabetes.

Jagadeeshaprasad Mashanipalya G MG Batkulwar Kedar B KB Meshram Nishita N NN Tiwari Shalbha S Korwar Arvind M AM Unnikrishnan Ambika G AG Kulkarni Mahesh J MJ

Clinical proteomics 20160329

<h4>Background</h4>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 ...[more]

PMID: 27030792

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Project description:Analytical methods and tools for the characterization of the human exposome by untargeted mass spectrometry approaches are advancing rapidly. Adductomics methods have been developed for untargeted screening of short-lived electrophiles, in the form of adducts to proteins or DNA, in vivo. The identification of an adduct and its precursor electrophile in the blood is more complex than that of stable chemicals. The present work aims to illustrate procedures for the identification of an adduct to N-terminal valine in hemoglobin detected with adductomics, and pathways for the tracing of its precursor and possible exposure sources. Identification of the adduct proceeded via preparation and characterization of standards of adduct analytes. Possible precursor(s) and exposure sources were investigated by measurements in blood of adduct formation by precursors in vitro and adduct levels in vivo. The adduct was identified as hydroxypropanoic acid valine (HPA-Val) by verification with a synthesized reference. The HPA-Val was measured together with other adducts (from acrylamide, glycidamide, glycidol, and acrylic acid) in human blood (n = 51, schoolchildren). The HPA-Val levels ranged between 6 and 76 pmol/g hemoglobin. The analysis of reference samples from humans and rodents showed that the HPA-Val adduct was observed in all studied samples. No correlation of the HPA-Val level with the other studied adducts was observed in humans, nor was an increase in tobacco smokers observed. A small increase was observed in rodents exposed to glycidol. The formation of the HPA-Val adduct upon incubation of blood with glycidic acid (an epoxide) was shown. The relatively high adduct levels observed in vivo in relation to the measured reactivity of the epoxide, and the fact that the epoxide is not described as naturally occurring, suggest that glycidic acid is not the only precursor of the HPA-Val adduct identified in vivo. Another endogenous electrophile is suspected to contribute to the in vivo HPA-Val adduct level.

Dataset Information

Targeted quantification of N-1-(carboxymethyl) valine and N-1-(carboxyethyl) valine peptides of ?-hemoglobin for better diagnostics in diabetes.

Publications

Targeted quantification of N-1-(carboxymethyl) valine and N-1-(carboxyethyl) valine peptides of β-hemoglobin for better diagnostics in diabetes.

Similar Datasets

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