HUMAN XENOBIOTIC-METABOLIZING ESTERASES IN LIVER AND BLOOD

Esterases in human liver microsomes hydrolysed fluazifop-butyl (V(max) 9.8 +/- 1.6 mumol/min/g tissue), paraoxon (V(max) 47.4 +/- 7.5 nmol/min/g tissue) and phenylacetate (V(max) 57 +/- 8 mumol/min/g tissue), whereas esterases found in the human liver cytosol hydrolysed fluazifop-butyl (V(max) 10.0 +/- 0.5 mumol/min/g tissue) and phenylacetate (V(max) 37 +/- 2.9 mumol/min/g tissue) but not paraoxon. Human plasma esterase hydrolysed fluazifop-butyl (V(max) 0.09 +/- 0.006 mumol/min/mL), paraoxon (V(max) 210 +/- 14 nmol/min/mL) and phenylacetate (V(max) 250 +/- 17 mumol/min/mL). Inhibitory studies using paraoxon, bis-nitrophenol phosphate and mercuric chloride indicated fluazifop-butyl hydrolysis involved carboxylesterase in liver microsomes and cytosol, and cholinesterase and carboxylesterase in plasma. Phenylacetate hydrolysis involved arylesterase in plasma, both arylesterase and carboxylesterase in liver microsomes and carboxylesterase in liver cytosol. Plasma hydrolysis is less important and overall esterase activity is lower in humans than in the rat which is therefore a poor model.