Esterase activity, DEHP

Because the metabolism of DEHP was catalyzed by so many fractions of the trout liver homogenate, these fractions were characterized by measurement of marker enzymes to determine which organelles actually were responsible for the observed DEHP metabolism. Succinic dehydrogenase activity was used as a marker for mitochondria, whereas glucose-6-phosphatase was used as a marker for microsomes. The distribution of DEHP oxidase activity (production of polar metabolites 1 and 2 with added NADPH) and of DEHP esterase activity (production of monoester without added NADPH) were also determined. It was found (Figure 2) that the distribution of DEHP oxidase activity parallels the distribution of microsomal activity and the distribution of DEHP esterase activity parallels the distribution of microsomal activity, but is also present in the cytosol fraction. 

Figure 2. Distribution of marker enzymes and DEHP-metabolizing enzymes in trout liver homogenate fractions. DEHP esterase and DEHP oxidase were each measured by 1-hr incubations of 0.010 ftmol of UC-DEHP in a total volume of 2 mL. Fraction (A), 2,000 g pellet (B), 10,000 g pellet (C), 100,000 g pellet and (D), 100,000 g supernatant. Relative Specific Activity = percent of total activity/ percent of total protein (14).

Fish liver microsomes are capable of both hydrolytic and oxidative metabolism of phthalate esters. In addition, trout liver cytosol and blood serum exhibited esterase activity against DEHP. 

No data were located regarding the metabolites produced in humans or animals after either inhalation or dermal exposures to DEHP. Metabolism following these routes of exposure is expected to be similar to that after oral exposures, since there are lipases present in the alveolar cells of the lungs and the epidermis. However, the activities of these lipases are about 20% of that for the pancreatic esterase secreted into the intestines (Albro et al. 1987), so it is possible that a larger portion of an absorbed dose from respiratory or dermal exposures to DEHP will initially be presented to the tissues as unhydrolyzed DEHP rather than MEHP. 

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