Disease relevance of HSDB 1179

• Oxidative N-demethylation was measured by incubation experiments using Bacillus megaterium isolated from topsoil as a biocatalyst for the N-demethylation of the N,N-dialkylarylamines N,N-dimethylaniline and N-ethyl-N-methylaniline [1].
• Subchronic (13-week) toxicity studies of N,N-dimethylaniline administered to Fischer 344 rats and B6C3F1 mice [2].
• Intrahepatic arterial infusion of 131I-labelled lipiodol was performed to study the intrahepatic distribution of lipiodol and to determine the radiation effect on 3'-Methyl-4-Dimethylaminobenzene (DAB) induced hepatocellular carcinoma (HCC) in rats [3].
• The subchronic toxicity of N,N-dimethylaniline (DMA) was studied by administration in corn oil by gavage at doses of 31.25, 62.5, 125, 250, 20, or 500 mg/kg body weight to groups of 10 male and 10 female F344 rats and B6C3F1 mice 5 d per week for 13 wk [2].

High impact information on HSDB 1179

• Complementary DNA (cDNA) clones encoding the adult human liver flavin-containing monooxygenase (FMO; dimethylaniline N-oxidase, EC 1.14.13.8) were isolated from lambda gt10 and lambda gt11 libraries [4].
• Ferric chloride-catalyzed activation of hydrogen peroxide for the demethylation of N,N-dimethylaniline, the epoxidation of olefins, and the oxidative cleavage of vicinal diols in acetonitrile: a reaction mimic for cytochrome P-450 [5].
• When the concentrations of both N,N-dimethylaniline and ethyl hydroperoxide were varied in a constant ratio a linear double reciprocal plot was obtained, which is consistent with a ping-pong kinetic mechanism for the horseradish peroxidase-catalyzed demethylation reaction [6].
• The dealkylation reaction exhibited normal Michaelis-Menten saturation kinetics with respect to N,N-dimethylaniline (Km = 0.08 mM) and ethyl hydrogen peroxide (Km = 0.8 mM) at low substrate concentrations [7].
• Addition of saturating amounts of N,N-dimethylaniline leads to a 3-fold increase of Vmax of NADPH utilization with 40% of these extra molecules providing electrons for the hydroxylation/N-demethylation sequence [8].

Biological context of HSDB 1179

• The turnover number for the ethyl hydrogen peroxide-supported dealkylation of N,N-dimethylaniline by chloroperoxidase (1476) was much greater than that for cytochrome P-450-catalyzed dealkylations [7].
• Adduct formation is inhibitory to the N-hydroxylation of 4-chloroaniline and N-demethylation of N,N-dimethylaniline; kinetic analysis suggests a competitive interaction at the catalytic site of the reactive revenast derivative with the tertiary arylamine [9].
• The incorporation and removal of cholesterol from microsomes was not followed by any essential changes in the rates of dimethylaniline N-demethylation, aniline p-hydroxylation, p-nitroanisole O-demethylation, oxygen consumption, oxidation of NADH and NADPH [10].
• Laser flash photolysis of IQ-FdUrd in Ar-purged aqueous solution with dimethylaniline as an electron donor gave rise to a transient absorption spectrum characteristic of semiquinone radical anion, which decayed via second order kinetics [11].
• A semi-empirical calculation (PM3) was applied to elucidate the anodic oxidation mechanism of N,N-dimethylaniline (DMA) and the dimerization of a cation radical (A) derived from DMA was ruled out [12].

Anatomical context of HSDB 1179

• The activity for N,N-dimethylaniline N-oxide was comparable to the microsomal activity, but the activity for imipramine N-oxide was much less than that in microsomes [13].
• The ratio of FMO (N-oxygenation)- to CYP (N-demethylation)-mediated metabolism of N,N-dimethylaniline decreased in liver microsomes from I3C- or DIM-fed rats from near unity to 0.02 at the highest dietary doses [14].
• Dietary selenium deficiency causes decreased N-oxygenation of N,N-dimethylaniline and increased mutagenicity of dimethylnitrosamine in the isolated rat liver/cell culture system [15].
• Inhibition of the FAD-containing dimethylaniline monooxygenase (FDMAM, EC 1.14.13.8) by N,N-dimethylbenzylamine (N,N-DMB) resulted in some increase in cyclophosphamide mutagenicity only in spermatids [16].
• Cumene hydroperoxide supported demethylation of N,N-dimethylaniline by cytochrome P-450 from adrenal cortex mitochondria [17].

Associations of HSDB 1179 with other chemical compounds

• The dealkylations of N,N-dimethylaniline by chloroperoxidase yielded N-methylaniline and formaldehyde in equimolar amounts with no other products detectable by high pressure liquid chromatography analysis of the reaction mixture [7].
• Upon excitation at 420 nm, photoinduced electron-transfer from the dimethylaniline donor to the singlet excited state of the anthracene acceptor occurs, as inferred from a combination of time-resolved fluorescence quenching and transient absorption measurements [18].
• The effect of D2O on the kinetic parameters for the hydroperoxide-supported N-demethylation of N,N-dimethylaniline catalyzed by chloroperoxidase and horseradish peroxidase was investigated in order to assess the roles of exchangeable hydrogens in the demethylation reaction [19].
• Monooxygenase activities such as epoxidation of styrene and N-demethylation of N,N-dimethylaniline, and catalase activity (dismutation of hydrogen peroxide) by wild-type Mb and the mutants, are examined by using H2O2 [20].
• The Km values for flavin-containing monooxygenase-mediated metabolism of N,N-dimethylaniline and methimazole were 2.8 and 0.8 mM, respectively, and the Km values for the oxidation of the antidepressants imipramine and fluoxetine were 20.9 and 9.8 microM, respectively [21].

Gene context of HSDB 1179

• 2. Hepatic microsomes of sexually mature fish contained NADPH-dependent FMO as evidenced by the conversion of N,N-dimethylaniline (DMA) to DMA-N-oxide, and immunorecognition of single bands (approximate apparent molecular weight of 55 kDa) by antibodies to mammalian FMO 1 and FMO 2 [22].
• Fluorescence quenching experiments carried out with N,N-dimethylaniline and 12-doxylstearic acid as quenchers showed that the 2-anthroyl chromophore was located in depth in the hydrophobic region of the lipid bilayer corresponding to the C9-C16 segment of the acyl chains [23].
• Further, preincubating human microsomes at 45 degrees C in the absence of NADPH for 4 min destroyed approximately 90% of the dimethylaniline N-oxidase activity [24].
• N,N-Dimethylaniline (DMA, CAS No. 121-69-7) and N,N-dimethyl-p-toluidine (DMPT, CAS No. 99-97-8) belong to the N-dialkylaminoaromatics, a chemical class structurally alerting to DNA reactivity [25].
• The other, indicated as NDMA-dependent alcohol dehydrogenase (NDMA-ADH), was purified to homogeneity [26].

Analytical, diagnostic and therapeutic context of HSDB 1179

• The method is based on direct analysis of quenched incubation mixtures by thin-layer chromatography and utilizes tritiated dimethylaniline as the substrate [27].
• The electron transfer from aniline and its N-methyl as well as N-phenyl substituted derivatives (N-methylaniline, N,N-dimethylaniline, diphenylamine, triphenylamine) to parent solvent radical cations was studied by electron pulse radiolysis in n-butyl chloride solution [28].
• ELISA screening does not specifically identify lidocaine or its metabolites, which include 3-hydroxylidocaine, dimethylaniline, 4-hydroxydimethylaniline, monoethylglycinexylidine, 3-hydroxymonoethylglycinexylidine, and glycinexylidine [29].

References