Tyrosine adducts

The recent study of Williams et al (2007) found that sarin, soman, cyclosarin, and tabun phosphylate a tyrosine residue on albumin in human blood. The tyrosine adducts with soman and tabun were detected in guinea pigs receiving therapy 7 days following subcutaneous administration of five times the LD50 dose of the respective nerve agent. VX also forms a tyrosine adduct in human blood in vitro but only at high concentrations. 

The intermediates that form in recombination reactions, with their tyrosine adducts possessing 3 -phosphoryl groups, are reminiscent of the intermediates that form in the reactions catalyzed by topoisomerases. This mechanistic similarity reflects deeper evolutionary relationships. Examination of the three-dimensional structures of recombinases and type I topoisomerases reveals that these proteins are related by divergent evolution despite little amino acid sequence similarity (Figure 27,40). From this perspective, the action of a recombinase can be viewed as an intermolecular topoisomerase reaction. In each case, a tyrosine-DNA adduct is formed. In a topoisomerase reaction, this... 

Tyrosine adducts were found in guinea pigs and marmosets poisoned with sarin, soman, cyclosarin, and tabun. VX, which is less reactive than other WNAs, formed an adduct in human plasma in vitro only at high concentrations (Williams et al., 2007 Black, 2010 Black and Read, 2013). Tyrosine adducts were less sensitive than ChE as biomarkers with respect to exposure levels but were more stable and did not undergo an aging reaction such as OP binding to serine esterases (Read et al.,... 

Tabun Blood Adduct to albiunin Tyrosine adduct LC-MS-MS Williams et al. (2007)... 

The OP adduct on tyrosine 411 of human albumin is stable. The half-life for decay of the soman-Tyr 411 adduct is 20 days at pH 7.4, 22°C (Li et al., 2008a). The chlorpyrifos oxon-Tyr 411 adduct is even more stable. After 7 months at 22°C in pH 7.4 buffer, 80% of the Tyr 411 was still labeled with diethoxyphosphate, which is the adduct formed by chlorpyrifos oxon. However, at pH 8.3 and 22°C, 50% had lost the OP label in 3.6 months. OP-albumin adducts stored at -80°C are stable indefinitely at pH 8.3, 7.4, and 1.5. One advantage of a stable OP-tyrosine adduct is that it will survive in an animal long enough to allow the generation of antibodies. Another advantage of a stable OP-tyrosine adduct is that detection of OP can be made on samples long after exposure. 

OPs bound to tyrosine do not age. Aging of OP adducts on AChE and BChE is defined as the loss of an alkoxy group from the phosphorus atom. No masses representing aged OP-tyrosine adducts have been foimd. 

Li, B., Eyer, R, Eddleston, M., et al., 2013b. Protein tyrosine adduct in humans self-poisoned by chlorpyrifos. Toxicol. Appl. Pharmacol. 269 (3), 215-225. 

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