Demethylase activity

Kubiak Is the demethylase active specifically in the sperm cell cycle ... 

Rodrigues, A.D. et al. 1996. [O-methyl 14C]naproxen O-demethylase activity in human liver micro-somes Evidence for the involvement of cytochrome P4501A2 and P4502C9/10. Drug Metab. Dispos. 24 126. 

In this study, P-450-related enzyme activities (benzphetamine N-demethylase, 7-ethoxycoumarin O-deethylase) were also measured in liver homogenates (prepared 24 hours after the last treatment) from rats treated orally with MEK for 1-7 days and compared to the activity obtained with phenobarbital treatment (80 mg/kg intraperitoneally for 3 days) (Robertson et al. 1989). Total cytochrome P-450 was also measured. No consistent change was noted in benzphetamine N-demethylase activity as the result of MEK treatment, while 7-ethoxycoumarin O-deethylase was over 3 times higher than controls and comparable to phenobarbital induction. Total P-450 levels were increased to approximately 150-200% of controls with MEK and to 570% of control by phenobarbital. The authors concluded that the potentiating effects of MEK on the neurotoxicity of -hexane appear to arise, at least in part, from the activating effects of MEK on selected microsomal enzymes responsible for -hexane activation. 

Stevens JT, Chernoff N, Farmer JD, et al. 1979. Perinatal toxicology of mirex administered in the diet II. Relation of hepatic mirex levels to induction of microsomal benzphetamine N-demethylase activity. Toxicol Lett 4(4) 269-274. 

Aoyama Y, Horiuchi T, Yoshida Y. 1996a. Lanosterol 14-demethylase activity expressed in rat brain microsomes. J Biochem (Tokyo) 120 982-986. 

Histone methylation is a relatively stable modification with a slow turnover rate. However, there is evidence of methyl group turnover for HeLa H3 [150]. It remains to be shown if this histone demethylase activity is present in transformed, but not normal cells. 

MBD2b a truncated version of MBD2a (translation stars at a second methionine codon in MBD2a) that lacks the (GR)n domain was reported to have demethylase activity with direct removal of the methyl group expressed in somatic tissues but not ES cells... 

A large number of histone lysine methylation sites have been characterized, showing that the trimethylated state is prevalent. Given that LSDl demethylates only mono- and dimethylated lysine substrates, it seemed likely that additional enzymes would catalyze such a reaction. Indeed, the recent discovery of proteins that harbor a JmjC domain and have demethylase activity revealed a novel family of enzymes that also contain other domains associated with chromatin remodeling. 

This release of formaldehyde can also be quantified by using formaldehyde dehydrogenase, as described above. An alternative way to determine demethylase activity by measuring the amounts of released formaldehyde is the use of the Nash reaction [68, 69]. This method is based on the formation of the colored 3,5-diacetyl-1,4-dihydropyridine by condensation of formaldehyde and acetylacetone in the... 

Our current knowledge regarding histone methylation stems in large part from the study of histone methyltransferases. Several of these enzymes are essential for development, vdth deregulated expression being linked to human disorders such as cancer [4]. Whereas proteins responsible for methylation of histones have been knovm for almost a decade, enzymes with histone demethylase activity (HDM) have only recently been discovered. Here we summarize our current knowledge regarding histone demethylases with a focus on the demethylation mechanisms, potential roles... 

Figure 13.5 The human Jumonji C family. Phylogenetic tree of the human JmjC domain containing proteins modified from Cloos et al. [3]. The domain structures of the proteins are indicated. The clusters for which histone lysine demethylase activity have been published are shown in gray. See text for details and references, jumonji C domain (JmjC) Jumonji...

Eq. 1 log A, logarithm of the percentage increase in ethylmorphine N-demethylase activity alcP, ratio of molecular area to depth-square AE, EL - Eu, difference between the energy of the lowest unoccupied to the highest occupied molecular orbital log P, logarithm of the octanol/water partition coefficient. 

In one-, four- and 13-week studies, the effects of coumarin treatment were compared in male Sprague-Dawley rats, CD-I mice and Syrian hamsters. Rats were fed 0-0.75% coumarin for one and four weeks and 0.5% coumarin for 13 weeks. Mice and hamsters were fed 0-0.5 and 0-1.0% coumarin, respectively, for one, four or 13 weeks. In the rat, coumarin caused dose-related hepatotoxic effects which included vacuolar degeneration, apoptosis and bile duct proliferation and increases in serum bilirubin content and both serum and hepatic y-glutamyltranspeptidase activity. A sustained stimulation of hepatocyte replicative DNA synthesis was observed in rats treated for four and 13 weeks. Levels of total hepatic glutathione were increased approximately twofold, and there were statistically significant decreases in microsomal cytochrome P450 content and ethylmorphine 7V-demethylase activity. These effects were reduced or not observed in mice and hamsters (Lake Grasso, 1996). 

N-demethylase activity was monitored by the CBT, and 7-N-demethylase activity was monitored by the caffeine urinary metabolite ratio (CMR). PBB-exposed subjects had higher CBT values (p<0.02) than urban nonsmokers, but tire values were comparable to those of urban smokers. The correlation between serum PBB levels and the CBT value was poor (r ().2). The CMR value in PBB-exposed subjects was also higher than that of urban nonsmokers (p<0.05) there was no correlation between serum PBB levels and CMR values. Generally, smokers have higher CBT values than nonsmokers due to the presence of polycyclic aromatic hydrocarbons (PAH) in tobacco smoke, which induce CYPIA (Kotake et al. 1982). 

Holtje HD, Fattorusso C. Construction of a model of the Candida albicans lanosterol 14-alpha-demethylase active site using the homology modelling technique. Pharm Acta Helv 1998 72 271-277. 

S. K. Bhattacharya, S. Ramchandani, N. Cervoni, and M. Szyf. A mammalian protein with specific demethylase activity for mCpG DNA. Nature, 397, 579 583, 1999. 

Additional studies with fetal guinea pig livers indicated a marked variation in cytochrome P450 and O-demethylase activity in individual fetal livers these findings correlated well with the concentration of liver... 

Figure 2. p-Nitroanisole O-demethylase activity in weanling guinea pigs given varying amounts of ascorbic acid (39). 

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