Soman cholinesterase binding

There is no correlation between AChE inhibition and the disposition of [ H]-soman, H)-DFP, and [ H]-sarin in brain (Kadar cf a/, 1985 Little etal., 1988). For example, the hypothalamus binds two to five times more OP compared to the striatum, but the striatum has more AChE activity than the hypothalamus. This suggests that in the hypothalamus, targets other than cholinesterase bind OP (Little et al., 1988). In a related experiment, binding of pH]-DFP to whole brain homogenate was decreased only 15% by preincubation with 1 pM eserine (a specific inhibitor of AChE and BChE), suggesting that only 15% of the DFP-Iabeled proteins are cholinesterases (Richards etal., 1999). 

These examples show that OPs can bind covalently to albumin under physiological conditions, and that the resultant adducts are relatively stable. OP-albumin adducts could therefore be useful as biomarkers of OP exposure. In addition, unlike cholinesterases, the soman-albumin conjugate does not age (Li et al, 2008a), making it possible to discriminate between sarin and soman exposure. OP-albumin adducts have not yet been reported in humans exposed to OPs. 

FIGURE 19.1 Chemical structures of nerve agents the nerve agents sarin (GB), soman (GD), and cyclosarin (GF) lose fluorine subsequent to binding to cholinesterase. The agents tabun (GA), VX, and Russian VX lose CN, and the thiol groups, respectively. 

---