The monohydroxylation of halobenzenes by phenobarbital-induced rat liver microsomes was studied. The.p-halophenol was found to be the major metabolite from all four halobenzenes; o-halophenol formation decreased as the halogen atom size increased. Vmasfor-total hydroxylation (ortho and para products) correlated well with the ar Hammett constant with a negative p value. This implies a positively charged intermediate in the rate-determining step. Vm.._ for either ortho orpara hydroxylation alone did not correlate with a Hammett constant, implying that the product-determining step occurs after the rate-determining step. Rate-determining formation of a radical cation intermediate is postulated to explain this data.Metabolism of monohalobenzenes, especially chlorobenzene and bromobenzene, has been the subject of literally scores of studies. These compounds are of interest not only as primary environmental contaminants but also because they serve as models for more structurally complex haloaromatics such as polychloro-and polybromobiphenyls and polyhalogenated diphenyldioxins and diphenylfurans (1). Our recent interest in the biological oxidation of heteroatoms (2-5) led us to consider the.possibility that oxidation of the halogen atom was the initial step in the cytochrome P-450-catalyzed metabolism of aromatic halides. Oxidation by removal of a hydrogen atom or an electron as an initial step in cytochrome P-450-catalyzed metabolism has been postulated for several substrates, including vinyl halides (6, 7), cyclopropyl amines (5, 8), sulfides (9), and norbornane (10). Evidence for a similar one-electron oxidation of aryl halides might be obtained from comparison of the kinetics of hydroxylation of the monohalobenzenes.Although the aryl halides are a thoroughly studied group of compounds, consultation of the literature revealed an almost complete lack of kinetic data concerning their in vitro metabolism. An excellent product study of chlorobenzene metabolism progressing in complexity from reconstituted soluble hemoprotein systems to perfused rat livers was reported by Selander et al. (11). A Lineweaver-Burk plot for the metabolism of bromobenzene by a supernatant obtained at 9,000 X g from rat liver can be found in a study by Zampaglione et al. (12). However, it became obvious that, to make a valid comparison of the hydroxylation kinetics for the monohalobenzenes, a set of data generated in one laboratory with microsomes from a single isolation and with a consistent method of acquiring and presenting the kinetic data would be required. MATERIALS AND METHODSAll chemicals were of the highest purity commercially available. Pentane was redistilled prior to use. Reduced pyridine nucleotide (NADPH) was obtained from Sigma; o-and m-iodoanisole were obtained by decomposing the corresponding diazonium salt with potassium iodide (13).Microsomes. Male Sprague-Dawley rats (80-100 g each) were treated with phenobarbital (0.1% in drinking water) for 5 days. Rats were then killed, and liver microsomes were prepared as descr...

No abstract

Several mammary and adipose enzymes were measured in normal, adrenal-ectomized, adrenalectomized cortisol-treated, and intake-restricted lactating rats. Acetyl-CoA carboxylase, lipoprotein lipase, and triglyceride synthetase complex activities in mammary tissue were unchanged by intake restriction, decreased by adrenalectomy, and increased by glucocorticoid-replacement therapy. Malic dehydrogenase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and lipoprotein lipase activities in adipose were unchanged after adrenalectomy.

The effect of varying feed intake and feeding pattern during the early postweaning period on growth, body composition and adipose tissue cellularity was studied in polygenic obese and control normal mice. Male mice were assigned to the following dietary treatments at 4.5 wk of age: stock diet fed ad libitum(AL), four palatable foods cafeteria-fed(CF), stock diet fed every 2 h by automatic feeders adjusted for maximum intake(MI), fed same procedure as MI but restricted to produce 70% of the gain of mice fed ad libitum(RE), and stock diet fed one meal/d the same amount fed RE mice(PM). Mice were killed after 5 wk on treatment. Cafeteria-fed control mice were heavier (P less than .05) than RE control mice, but they were not different (P greater than .05) from AL, MI and PM control mice, while CF obese mice were heavier and RE obese mice were smaller than AL, MI and PM obese mice (P less than .05). Cafeteria-fed mice were fatter than mice from all other treatments in both the obese and control lines. Maximum intake, PM and RE mice were fatter than AL mice but this effect was only significant in the obese line. Alterations in feeding pattern can affect body composition even though body weight may not show a correlated response. Cafeteria-fed obese mice had larger fat pads and more small (less than 40 micron) and large (greater than 110 micron) adipocytes than other obese mice. Results indicate that the difference in the development of obesity on cafeteria diet was due primarily to genetic effects while the increase in percentage fat after restriction on MI, PM and RE treatments was due mainly to the acute change of feeding pattern.

No abstract