Showing papers on "Demethylase published in 1984"

An estrogen-dependent demethylation at the 5′ end of the chicken vitellogenin gene is independent of DNA synthesis

Abstract: A HpaII site 611 base pairs upstream from the 5' end of the chicken vitellogenin II gene exhibits an estrogen-dependent demethylation in hormone-responsive cells. The complete demethylation of this site occurs considerably later than the transcriptional activation of the gene, and therefore appears to be an effect rather than a cause of this activation. In vivo studies using two inhibitors of DNA synthesis (cytosine arabinoside and hydroxyurea) demonstrate that activation of transcription of the gene is independent of DNA synthesis. Surprisingly, the estrogen-dependent demethylation of the HpaII site is also independent of DNA synthesis. The possible involvement of a site-specific demethylase is discussed.

Sensory transduction in Escherichia coli: regulation of the demethylation rate by the CheA protein.

Abstract: The reversible methylation of three membrane proteins plays an essential role in bacterial chemotaxis. Chemotactic stimuli bring about changes in the levels of methylation of these proteins, at least in part, by regulation of the demethylation reaction. Addition of attractants causes an increase in the methylation level and a transient, but essentially complete, inhibition in the rate of the demethylation reaction, while addition of repellents results in a decrease in level and a transient increase (of at least 25- to 30-fold) in rate. We have now found that the increase, but not the decrease, in rate requires the presence of the cheA gene product, a protein that is distinct from the demethylase. The demethylation reaction is therefore regulated by two distinct mechanisms--one, which involves the CheA protein, that mediates the increase in rate and a second, which does not involve the CheA protein, that mediates the decrease in rate. Several pieces of evidence already in the literature imply that the CheA protein functions downstream of the methylation system at the flagellar end of the chemotactic machinery. These data, in conjunction with the newer results, suggest that the CheA protein helps to regulate the demethylation reaction through a feedback mechanism.

Hepatic microsomal enzymes in S. mansoni infected mice: II. Effect of duration of infection and lindane administration on aminopyrine demethylase and aniline hydroxylase.

Abstract: The time course of effects of S. mansoni infection on hepatic microsomal drug metabolizing enzymes was studied in swiss albino mice. Aminopyrine demethylase and aniline hydroxylase showed increases in activity, reaching a peak 30 days post infection. Both enzymes demonstrated a steady decline thereafter. On day 60, the level of aminopyrine demethylase was comparable to that of unifected mice. On the other hand, the activity of aniline hydroxylase was lower than the control values. Treatment with lindane (40 mg/Kg/day × 3) increased the activity of both enzymes after different durations of disease induction. Changes in hepatic microsomal enzymes in S. mansoni infection may alter the intensity and duration of pharmacologie or toxic effects of drugs eliminated from the body through metabolic transformation.

Nature of N-nitrosodimethylamine demethylase in hepatic microsomes of rats.

Abstract: The nature of enzymes involved in demethylation of N-nitrosodimethylamine (NDMA) was investigated in hepatic microsomes of rats. Compared to the other cytochrome P-450-dependent enzymes. NDMA demethylase had anomalous properties as reported in the literature. However, kinetic analysis suggested a qualitative change in NDMA demethylase induced by phenobarbital (PB) and 3-methylcholanthrene (MC) pretreatment. The inhibition of demethylase by alpha-naphthoflavone in MC-treated microsomes also suggested that cytochrome P-450 species induced by MC are active in demethylating NDMA. The enhancement of NDMA demethylase activity by metyrapone in PB-treated microsomes was greater than in non-treated ones, and was not observed in MC-treated ones. The result is almost the same as in acetanilide hydroxylation, depending on cytochrome P-450. Pyrazole, tranylcypromine, and aminoacetonitrile, which are selective inhibitors of NDMA demethylation, interacted with cytochrome P-450 species to produce type-II spectra, and typical type-II compounds (aniline, imidazole, and nicotinamide) were inhibitors of the NDMA demethylation. Tranylcypromine irreversibly inhibited microsomal monoamine oxidase [EC 1.4.3.4], but not NDMA demethylase. Semicarbazide (a copper- and pyridoxal-containing amine oxidase [EC 1.4.3.6] inhibitor) had no effect on demethylation. From these results it is concluded that NDMA demethylation depends only on cytochrome P-450-dependent monooxygenases.

Metabolism of nitrosamines by cytochrome P-450 isozymes.

Abstract: Results are presented to show that N-nitrosodimethylamine demethylase is P-450 mediated and N-nitrosodimethylamine is efficiently metabolized by specific P-450 isozymes inducible by a group of new inducers. The P-450-mediated N-nitrosodimethylamine demethylase also responds differently to inhibitors when activities are compared with those of classical monooxygenase systems.

Effects of Riboflavin on the Dimethylnitrosamine Demethylase System in the Rat Liver

Abstract: The effects of riboflavin on the dimethylnitrosamine [(DMN) CAS: 62-75-9; N-nitrosodimethylamine] demethylase system in inbred F344 rat liver were investigated. Dietary riboflavin deficiency markedly stimulated the activity of DMN demethylase I operating at a low substrate concentration (4 mM), but it caused no change in the activity of DMN demethylase II operating at a high substrate concentration (200 mM). This effect could be reversed by short-term supplementation of the vitamin by a series of three ip injections (0.5 mg/dose/day) to the deficient animals. This dosage regimen of riboflavin did not change the activity of DMN demethylase I in the normal animals. The study in vitro demonstrated that flavins were inhibitory to DMN demethylase I. The enzyme activity in the microsomes of both control and deficient animals was inhibited by preincubation with flavins, suggesting that the interaction between flavins and the enzyme rendered the enzyme inactive. Flavin adenine dinucleotide (FAD) appeared to have a more pronounced effect than riboflavin. In agreement with the earlier observation, DMN demethylase II was unaffected by FAD or riboflavin.