Sökning: onr:"swepub:oai:DiVA.org:su-163561" >
Discovery of Novel ...
Discovery of Novel N-(4-Hydroxybenzyl)valine Hemoglobin Adducts in Human Blood
-
Degner, Amanda (författare)
-
- Carlsson, Henrik (författare)
- Stockholms universitet,Institutionen för miljövetenskap och analytisk kemi
-
- Karlsson, Isabella (författare)
- Stockholms universitet,Institutionen för miljövetenskap och analytisk kemi
-
visa fler...
-
- Eriksson, Johan (författare)
- Stockholms universitet,Institutionen för miljövetenskap och analytisk kemi
-
Pujari, Suresh S. (författare)
-
Tretyakova, Natalia Y. (författare)
-
- Törnqvist, Margareta (författare)
- Stockholms universitet,Institutionen för miljövetenskap och analytisk kemi
-
visa färre...
-
(creator_code:org_t)
- 2018-10-30
- 2018
- Engelska.
-
Ingår i: Chemical Research in Toxicology. - : American Chemical Society (ACS). - 0893-228X .- 1520-5010. ; 31:12, s. 1305-1314
- Relaterad länk:
-
https://europepmc.or...
-
visa fler...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- Humans are exposed to a wide range of electrophilic compounds present in our diet and environment or formed endogenously as part of normal physiological processes. These electrophiles can modify nucleophilic sites of proteins and DNA to form covalent adducts. Recently, powerful untargeted adductomic approaches have been developed for systematic screening of these adducts in human blood. Our earlier untargeted adductomics study detected 19 unknown adducts to N-terminal valine in hemoglobin (Hb) in human blood. We now describe a full characterization of one of these adducts, which corresponds to the addition of a 4-hydroxybenzyl (4-OHBn) group to N-terminal valine in Hb to form N(4-hydroxybenzyl)valine (4-OHBn-Val). The adduct structure was determined by comparison of its accurate mass, HPLC retention time, and MS/MS fragmentation to that of authentic standards prepared by chemical synthesis. Average 4-OHBn-Val adduct concentrations in 12 human blood samples were estimated to 380 +/- 160 pmol/g Hb. Two possible routes of 4-OHBnVal adduct formation are proposed using two different precursor electrophiles: 4-quinone methide (4-QM) and 4-hydroxybenzaldehyde (4-OHBA). We found that 4-QM reacts rapidly with valine to form the 4-OHBn-Val adduct; however, the quinone methide is unstable under physiological conditions due to hydrolysis. It was shown that 4-OHBA forms reversible Schiff base adducts with valine, which can be stabilized via reduction in blood generating the 4-OHBn-Val adduct. In addition, trace amounts of isomeric 2-hydroxybenzyl-valine (2-OHBn-Val) adducts were detected in 12 human blood samples (estimated mean adduct level, 5.0 +/- 1.4 pmol/g Hb). Further studies are needed to quantify the contributions from identified possible precursor electrophiles to the observed hydroxybenzyl adducts in humans.
Ämnesord
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas