Fatty acid anilides: In vivo formation and relevance to toxic oil syndrome

Purification and characterization of rat hepatic microsomal low molecular weight fatty acid ethyl ester synthase and its relationship to carboxylesterases

“…We have also found that phenobarbital induces FAEE synthase and PNPA-hydrolyzing activities (unpublished data) and reported an identical inhibition profile of FAEE synthase, fatty acid methyl ester synthase, fatty acid anilide synthase, and PNPA-hydrolyzing activities by tri-o-tolyl phosphate (TOTP) (an inhibitor of hepatic besterases) in HepG2 (human hepatocellular carcinoma) cells [37]. Although hepatic CEs are structurally and functionally different than pancreatic cholesterol esterase, both enzymes catalyze the synthesis and hydrolysis of esters and amide bonds [10,37]. The LMW proteins purified in the present study, which express FAEE synthase as well as PNPA-hydrolyzing activity, are most probably various isozymes of CEs, which exist as monomers.…”

“…Previous studies have shown that rat adipose tissue microsomes and the liver homogenate fractions catalyze the formation and breakdown of ethyl palmitate, respectively [35,36]. A number of studies reported in the last 20 years, including studies from our laboratory, indicate that CEs, ChE, and lipases are involved in synthesis and/or hydrolysis of fatty acid esters of several endogenous and exogenous substrates [9][10][11][12]37]. The results of purification and characterization of FAEE synthase from rat adipose tissue [25] and hepatic microsomal fraction [9] indicate that FAEE synthase activity is expressed by CEs.…”

“…Synthetic and/or hydrolytic activities toward xenobiotic esters, amides, and thioesters have been reported in a wide variety of mammalian tissues [1][2][3][4][5][6][7][8][9][10][11]. A number of fatty acid esters of xenobiotic alcohols have been isolated and identified from human and animal tissues [8,12,13].…”

“…Rat liver microsomal high molecular weight (HMW) FAEE synthase (ca. 180 kD), which we purified, catalyzes the synthesis of 2-chloroethyl oleate, oleyl anilide, and 2-butoxyethyl oleate [8][9][10] and has been found to be similar to rat hepatic microsomal carboxylesterase (CE, pI 6.1) [24] and rat adipose tissue FAEE synthase [25]. A relatively minor and low molecular weight (LMW) protein fraction of digitonized rat liver microsomes eluted by gel filtration (GF) column chromatography, which expressed FAEE synthase and fatty acid 2-chloroethyl ester (FACEE) synthase activities [9], was further purified and characterized in the present study.…”