Lauric acid hydroxylases

Diet (%) Intake (mg/kg bw per day) Relative liver weight (% increase over controls) Peroxisomal pahnitoyl-CoA oxidation (increase over control) Microsomal lauric acid hydroxylase (increase over control) ... 

Peroxisome proliferator-activated receptors (PPARs) comprise another subfamily of nuclear receptors whose members regulate the transcription of genes controlling fatty acid oxidation, including CYP4A (lauric acid hydroxylases). PPAR a, /3 (also known... 

CaJacob, C.A. and P.R. Ortiz de Montellano (1986). Mechanism-based in vivo inactivation of lauric acid hydroxylases. Biochemistry 25, 4705-4711. 

S.A. Wrighton, and R.T. Okita (1995). Human liver lauric acid hydroxylase activities. Drug Metab. Dispos. 23, 1037-1043. 

CYP119A1 Sulfolobus solfataricus 1F4T, 1F4U, 1109, 1107 4-Phenylimidazole Fatty acid (e.g., lauric acid) hydroxylase, styrene epoxidase [91, 92]... 

Powell PK, Wolf I, Lasker JM. Identification of CYP4A11 as the major lauric acid omega-hydroxylase in human fiver microsomes. Arch Biochem Biophys 1996 335( 1 ) 219—226. 

This enzyme [EC 1.14.15.3], also known as alkane 1-monooxygenase, lauric acid ca-hydroxylase, fatty acid hydroxylate fatty acids in the [Pg.47]

Treatment of five-week-old male Sprague-Dawley rats with 1000 mg/kg bw di(2-ethylhexyl) phthalate per day by gavage for 14 days caused increased relative liver weight and hepatic peroxisome proliferation (Lake et al., 1984). In addition, di(2-ethylhexyl) phthalate treatment induced cyanide-insensitive palmitoyl-coenzyme A (CoA) oxidation activity and microsomal lauric acid 12-hydroxylase activity in the... 

The hepatic effects of cinnamyl anthranilate were evaluated in male CD 1 mice and male Fischer 344 rats treated by intraperitoneal injection for three consecutive days (Viswalingam Caldwell, 1997). At doses of 100 and 1000 mg/kg bw per day, relative liver weights of mice increased by 22% and 50%, respectively, 24 h after the final dose and peroxisomal (cyanide-insensitive) palmitoyl-coenzyme A (CoA) oxidation activity increased fivefold at both levels. Microsomal lauric acid 11- and 12-hydroxylase activity (CYP4A) was increased 15-fold at 100 mg/kg bw per day and 17-fold at 1000 mg/kg bw per day. Limited evaluation indicated that cirmamyl anthmilate increased the size and number of peroxisomes in electron micrographs of hepatocytes of treated mice. In rats, relative liver weights and peroxisomal palmitoyl-CoA oxidation activity were significantly increased only at 1000 mg/kg bw per day (22% and twofold, respectively). 

Finally, since fatty acid hydroxylations at the o), 00-1, 00-2, 00-3, and co-4 positions also occur in plants and bacteria °, acetylenic fatty acids have also been employed to examine whether these hydroxylases are mechanistically similar to their mammalian counterparts and/or to identify the role of specific plant and bacterial P450 enzymes °. Thus, midchain and terminal acetylenes such as 10-dodecynoic acid have been used as probes of plant lauric acid oo-hydroxylases . Similarly, 17-ODYA has been shown to inactivate P450g, 3 (CYP108), an enzyme that hydroxylates fatty acids at positions other than the terminal (oo) carbon, through a heme alkylation mechanism . 

Helvig, C., C. Alayrac, C. Mioskowski, D. Koop, D. Poullain, F. Durst et al. (1997). Suicide inactivation of cytochrome P450 by midchain and terminal acetylenes. A mechanistic study of inactivation of a plant lauric acid omega-hydroxylase. J. Biol. Chem. 272,414-121. 

N.O. Reich, and P.R. Ortiz de Monteilano (1984). Autocatalytic inactivation of plant cytochrome P-450 enzymes Selective inactivation of the lauric acid in-chain hydroxylase from Helianthus tuberosus L. by unsaturated substrate analogs. Arch. Biochem. Biophys. 232, 1-7. 

Powell, P.K., I. Wolf, and J.M. Lasker (1996). Identification of CYP4A11 as the major lauric acid co-hydroxylase in human liver microsomes. Arch. Biochem. Biophys. 335, 219-226. 

CaJacob, C.A., W.K. Chan, E. Shepard, and P.R. Ortiz de Montellano (1988). The catalytic site of rat hepatic lauric acid omega-hydroxylase. Protein versus prosthetic heme alkylation in the omega-hydroxylation of acetylenic fatty acids. J. Biol Chem. 263, 18640-18649. 

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