Abstract:
:A common method to assess exposure to 1,3-butadiene through both occupational and environmental routes involves the detection of hemoglobin adducts formed by the primary reactive metabolite butadiene monoxide (EB). This assay is a modification of the Edman degradation procedure, which was developed to determine adducts formed specifically at the amine group of the N-terminal valine of hemoglobin. The goals of the current research are to determine the global modification of alpha- and beta-globin chains by EB and to localize the primary reactive residues to specific regions of the globin polypeptides. The degree of modification was monitored by electrospray mass spectrometry, which was used to measure the formation of EB-hemoglobin adducts (up to ten adducts per globin). Structural analysis of these modifications was performed by peptide mapping of globin peptides after trypsin digestion using liquid chromatography-mass spectrometry. These experiments provided information as to the relative reactivity of alpha- and beta-globin towards EB, as well as to the localization of adducts to specific peptide sequences. The results reveal variable reactivities of alpha- and beta-globin towards EB and also show the formation of multiple adducts at several alpha- and beta-globin sites. In addition, it is established that the N-terminal valine residues are not the first to be modified by EB.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Moll TS,Harms AC,Elfarra AAdoi
10.1016/s0009-2797(01)00206-xsubject
Has Abstractpub_date
2001-06-01 00:00:00pages
667-74eissn
0009-2797issn
1872-7786pii
S000927970100206Xjournal_volume
135-136pub_type
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