Structure-activity relationships in the hydrolysis of acrylate and methacrylate esters by carboxylesterase in vitro

Article abstract of DOI:10.1016/S0300-483X(96)03540-8

Acrylate esters are important chemicals in the plastics industry, whose toxicity is theorized to involve alkylation of critical cellular nucleophiles via the Michael addition. Carboxylesterase-mediated hydrolysis of acrylates may be a detoxification mechanism as the unsaturated acid produced is not electrophilic under physiological conditions. Using purified porcine liver carboxylesterase, the enzymatic hydrolysis of several acrylate eaters was characterized to determine K(m) and V(max) values for each ester. The K(m) (μM) and V(max) (nmol/min) values observed for ethyl acrylate were 134 ± 16 (S.D.) and 8.9 ± 2.0, respectively. While the K(m) for ethyl methacrylate was not significantly different, the V(max), 5.5 ± 2.5, was significantly lower compared with the corresponding value for ethyl acrylate. The K(m) and V(max) for butyl acrylate were 33.3 ± 8.5 μM and 1.49 ± 0.83 nmol/min, respectively, and the corresponding values for its α-methyl analog were not significantly different. The K(m) and V(max) for tetraethyleneglycol dimethacrylate were 39 ± 15 μM and 2.9 ± 1.0 nmol/min, respectively. The V(max) for ethyleneglycol dimethacrylate, 6.9 ± 2.4 nmol/min, was significantly higher than that of the larger bifunctional ester tetraethyleneglycol dimethacrylate, but the K(m) was not significantly different. These results indicate that α-methyl substitution appears to have a minor effect in the enzymatic hydrolysis of acrylates, and suggest that the relative toxicity of acrylates is not due to differences in carboxylesterase-mediated hydrolysis.