Showing papers on "Demethylase published in 1976"
TL;DR: The experiments demonstrate conclusively that CCl 3 -Cl bond cleavage and covalent binding of products of CCl 4 metabolism do not constitute a mechanism for loss of microsomal glucose 6-phosphatase, cytochrome P-450 or aminopyrine demethylase for the particular anaerobic conditions employed in vitro.
149 citations
TL;DR: Homogenates from germinating castor bean endosperm were fractionated by sucrose density gradient centrifugation and when challenged with a number of potential inhibitors the enzymes responded in ways fairly typical of mixed function oxidases from other plants and animals.
72 citations
TL;DR: The results of these studies reveal important differences between the properties of the enzymatic systems which metabolize DMN and mixed function oxidase substrates, and are consistent with the conclusion that the degradation of DMN to formaldehyde by rat liver preparations is a multicomponent system not rate limiting with respect to cytochrome P-450.
68 citations
TL;DR: The results suggest a failure in haem biosynthesis and/or an accelerated breakdown of existing haem in adjuvant-induced arthritic rats, which might have been caused by the breakdown of certain haem compounds.
50 citations
TL;DR: Microsomal activation of DMN to a mutagen and DMN demethylase appear to involve both cytochromes P-450 and P-448.
Abstract: The relationship between microsomal dimethylnitrosamine (DMN) demethylase activity and the capacity of isolated hepatic microsomes to activate DMN to a mutagen was examined using microsomes from C57 and DBA/2 mice which had been exposed to three different types of microsomal enzyme inducers: phenobarbital, which induces cytochrome P-450, 3-methylcholanthrene, which induces cytochrome P-448, and the polychlorinated biphenyl, Aroclor 1254 which appears to induce both types of cytochromes. DMN induced mutagenesis was assayed by a Salmonella auxotroph reversion test. With the C57 mice all three inducers increased both the activity of microsomal DMN demethylase and the capacity of the microsomes to activate DMN mutagenicity. In each case, however, the increase in mutagenicity was disproportionately greater than the increase in DMN demethylase activity. This was particularly evident with microsomes prepared from Aroclor induced mice. Microsomes from 3-methylcholanthrene treated DBA/2 mice were not induced for DMN demethylase or the activation of DMN mutagenicity. In addition the capacity of Aroclor to function as an inducer was relatively poor in this strain. Both DMN demethylation and mutagenesis were inhibited by the addition of either SKF 525-A or benzo(a)pyrene to the reaction mixtures. Thus microsomal activation of DMN to a mutagen and DMN demethylase appear to involve both cytochromes P-450 and P-448.
39 citations
TL;DR: Five potential intermediates of lanosterol have been synthesized for the first time and labelled with 3 H and each was extensively converted both to a more polar compound and to the corresponding 3β,15-diol diester.
30 citations
TL;DR: Nitrososarcosine rapidly inhibited DMN dem methylase activity, and induced statistically significant inhibitory effects at doses far below threshold levels for inhibition of aminopyrine demethylase.
6 citations
Journal Article•
TL;DR: The enzymes of the microsomal-bound 4-methyl sterol demethylase of cholesterol biosynthesis appear to be very similar in liver and these 2 Morris hepatomas, and regulation of the activity of the multienzymic system contained in the tumors may be altered.
Abstract: Previously, we reported that the rate of metabolism of methyl sterol intermediates of cholesterol biosynthesis by broken-cell preparations of Morriss hepatoma 7777 is very slow, whereas the intact tumors are known to synthesize cholesterol quite efficiently. Active preparations have now been obtained by substitution of pyrophosphate for phosphate buffer. Although substitution of pyrophosphate buffer markedly enhances microsomal methyl sterol demethylation rates 3- to 4-fold in hepatoma 7777, other microsomal enzymes and electron carriers in either liver or a more slowly growing hepatoma appear to be unaffected by pyrophosphate. Several properties of the active microsomal methyl sterol demethylase have now been compared for control rat liver, host liver, tumor 7777, and tumor 5123C. Conditions necessary for the assay of initial velocities of enzymic reactions in the tumor microsomes have been established with respect to the amount of protein, time-course, concentrations of cofactors and substrate, pH, and other variables. The K'm and the responses to the variables studied above are very similar for methyl sterol demethylase of microsomes isolated from control liver, host liver, tumor 5123C, and tumor 7777. The multienzymic demethylase in the various preparations has been found to be inhibited similarly by in vitro additions of cyanide, cytochrome c, and bile salts. Thus, the enzymes of the microsomal-bound 4-methyl sterol demethylase of cholesterol biosynthesis appear to be very similar in liver and these 2 Morris hepatomas. When xenobiotic inducers of microsomal oxidases, such as phenobarbital and methylcholanthrene, are administered to normal and tumor-bearing rats, elevated rates of methyl sterol demethylation are observed with isolated liver microsomes obtained from both normal and tumor-bearing rats. Similar increases are not observed in the tumors. Furthermore, daily administration of an intestinal bile acid sequestrant elevates hepatic methyl sterol demethylase, but statistically significant changes were not observed in tumors 7777 and 5123C. Since the enzymes of methyl sterol demethylase appear to be grossly similar in liver and these hepatomas, regulation of the activity of the multienzymic system contained in the tumors may be altered. On the other hand, these agents in vivo simply may not affect liver and the hepatomas similarly, due to a lack of uptake of the foreign substances by the tumor that has been transplanted to the thighs.
5 citations