Methyl deficiency

DiziK M, CHRISTMAN J K andwAiNFAN E (1991) Alterations in expression and methylation of specific genes in livers of rats fed a cancer promoting methyl-deficient diet . Carcinogenesis, 12, 1307-12. 

POGRIBNY J P, BASNAKIAN A G, MILLER B J, LOPATINA N G, POIRIER L A and JAMES S J (1995) Breaks in genomic DNA and within the P5 3 gene are associated with hypomethy lation in livers of folate/methyl-deficient rats . Cancer Res, 55, 1894-901. 

N-terminal methylation of proteins is possible and can play a major role in mitosis. Chen etal. discovered that the N-terminal serine or proline of regulator of chromatin condensation 1 (RCCl) is methylated. RCCl associates with chromatin, binding to histones H2 A and H2B, regulated by Ran, a GTPase. " For methylation to occur, the initiating methionine must be removed and a proline and lysine must be at positions 3 and 4, respectively. If RCCl is N-terminal methylation deficient, its binding to histones loses efficiency, which can cause spindle pole defects and ultimately cause problems in cell division. This work suggests the first known function for N-terminal protein methylation. ... 

Pogribny, I.P., Tryndyak, V.P., Muskhelishvili, L., Rusyn, I. and Ross, S.A. (2007) Methyl deficiency, alterations in global histone modifications, and carcinogenesis. The Journal of Nutrition, 137, 2168-222. 

Pogribny, I. P, Ba.snakian, A Miller, B., Lopatina, N Proirier, L, A., and James, S. J. (1SI95). Breaks in genomic DNA and within ihe p33 gene arc as.sociated with hypomethyiahon in livers of folate/methyl-deficient rats. Cancer Kes. 55,1894-1901. 

Okoji RS, Yu RC, Maronpot RR, Froines JR (2002) Sodium arsenite administration via drinking water increases genome-wide and Ha-ras DNA hypomethylation in methyl-deficient C57BL/6J mice. Carcinogenesis 23(5) 777-785... 

Christman, J. K. et al., Reversibility of changes in nucleic acid methylation and gene expression induced in rat liver by severe dietary methyl deficiency, Carcinogenesis, 14, 551-557, 1993. 

Several enzymatic and chemical modifications which could affect the properties, and hence the function, of tRNA s have been mentioned (Section II,C). Methyl-deficient tRNA has been shown to vary from normal tRNA in its amino acid acceptance and coding properties [43,44]. Nevertheless, despite indications of changes in methylase levels and specificity in a variety of differentiating systems (reviewed in reference [45]), the involvement of these enzymes in regulatory mechanisms remains unproved. Indeed Kay and Leboy[46], after a close examination of methylases from adult and newborn mice and from several tumors, suggested that neither tumor and normal extracts, nor different normal organs, could be unequivocally distinguished by either the rate or extent of the observed methylation. 

Acrylic Resins. The first synthetic polymer denture material, used throughout much of the 20th century, was based on the discovery of vulcanised mbber in 1839. Other polymers explored for denture and other dental uses have included ceUuloid, phenolformaldehyde resins, and vinyl chloride copolymers. Polystyrene, polycarbonates, polyurethanes, and acryHc resins have also been used for dental polymers. Because of the unique combination of properties, eg, aesthetics and ease of fabrication, acryHc resins based on methyl methacrylate and its polymer and/or copolymers have received the most attention since their introduction in 1937. However, deficiencies include excessive polymerization shrinkage and poor abrasion resistance. Polymers used in dental appHcation should have minimal dimensional changes during and subsequent to polymerization exceUent chemical, physical, and color stabiHty processabiHty and biocompatibiHty and the abiHty to blend with contiguous tissues. 

As a result of the 7r-deficiency of the pteridine nucleus, alkyl pteridines are activated in the a-positions. The common reactions based on C—H acidity are found with a wide variety of compounds. Bromination of 6- and 7-methyl groups leads to mono- and di-substitution selective formation of the monobromomethyl derivatives has not yet been achieved satisfactorily. 6-Methylisoxanthopterin is claimed to give the 6-bromomethyl derivative with bromine in acetic and sulfuric acids at 100 °C for 2 min (50ZN(B)132) and with 1,7-dimethyl-lumazine a 90% yield of the 7-bromomethyl derivative (60CB2668) is obtained after 4h... 

Alkyl radicals produced by oxidative decarboxylation of carboxylic acids are nucleophilic and attack protonated azoles at the most electron-deficient sites. Thus imidazole and 1-alkylimidazoles are alkylated exclusively at the 2-position (80AHC(27)241). Similarly, thiazoles are attacked in acidic media by methyl and propyl radicals to give 2-substituted derivatives in moderate yields, with smaller amounts of 5-substitution. These reactions have been reviewed (74AHC(i6)123) the mechanism involves an intermediate cr-complex. 

Homolytic cleavage of dlazonlum salts to produce aryl radicals is induced by titan1um(III) salt, which is also effective in reducing the a-carbonylalkyl radical adduct to olefins, telotnerization of methyl vinyl ketone, and dimerization of the adduct radicals. The reaction can be used with other electron-deficient olefins, but telomerization or dimerization are important side reactions. 

LPG is considered to be non-toxic witli no chronic effects, but the vapour is slightly anaesthetic. In sufficiently high concentrations, resulting in oxygen deficiency, it will result in physical asphyxiation. The gases are colourless and odourless but an odorant or stenching agent (e.g. methyl mercaptan or dimethyl sulphide) is normally added to facilitate detection by smell down to approximately 0.4% by volume in air, i.e. one-fifth of the lower flammable limit. The odorant is not added for specific applications, e.g. cosmetic aerosol propellant. 

The acetoxy dienone (218) gives phenol (220). Here, an alternative primary photoreaction competes effectively with the dienone 1,5-bonding expulsion of the lOjS-acetoxy substituent and hydrogen uptake from the solvent (dioxane). In the case of the hydroxy analog (219) the two paths are balanced and products from both processes, phenol (220) and diketone (222), are isolated. In the formation of the spiro compound (222) rupture of the 1,10-bond in the dipolar intermediate (221) predominates over the normal electron transmission in aprotic solvents from the enolate moiety via the three-membered ring to the electron-deficient carbon. While in protic solvents and in 10-methyl compounds this process is inhibited by the protonation of the enolate system in the dipolar intermediate [cf. (202), (203)], proton elimination from the tertiary hydroxy group in (221) could reverse the efficiencies of the two oxygens as electron sources. 

Reactions of fluorinated dipolarophiles. Electron-deficient unsaturated species generally make better dipolarophiles, therefore, fluonnated alkenes become better dipolarophiles when vinylic fluonnes are replaced by perfluoroalkyl groups For example, perfluoro-2-butene is unreactive with diazomethane, but more highly substituted perfluoroalkenes, such as perfluoro-2-methyl-2-pentene, undergo cycloadditions in high yields [5] (equation 2) Note the regiospecificity that IS observed in this reaction... 

Cycloaddition reactions where bis(trifluoromethyl)-substituted hetero-1,3-dienes act as dienophiles have been descnbed for open-chain and cyclic dienes [115, 126, 127] The balance of the diene -dienophile activity of bis(tnfluoro-methyl)-substituted hetero-l,3-dienes can be influenced strongly by the substituents bonded to the inuno nitrogen atom For instance, A/-(arylsulfonyl) denvatives of tnfluoroacetaldimine and hexafluoroacetone imine do not act as dienes but exhibit only the dienophile reactivity of electron deficient imines [5 229, 234,235, 236 237] (equation 52)... 

Still another possibility of isomerization is illustrated by the easy interconversions between pentaphenylpentadienoie aeid chloride and 2-chloropentaphenyl-3-eyelopenten-l-one. Interestingly, 2,4,6-trimethylpjrrylium iodide maj be sublimed without decomposition in a vacuum, possibly as a covalent 6-iodo-4-methyl-3,5-heptadien-2-one or 2-iodo-2,4,6-trimethyl-2H-pyran valenee isomer. In a related case, chlorocyclopropenes are covalent and are converted into cyclo-propenium derivatives only by the action of Friedel-Crafts catalysts (electron-deficient metallic chlorides) (ef. also Section II,C, 2,c.)... 

The highly 7r-deficient character of the 1,2,4-triazine ring increases the nucle-ophilicity of the methyl group in methyl-1,2,4-triazine A-oxides in reactions with electrophilic alkenes and aldehydes. Thus treatment of the 6-methyl-3-phenyl-1,2,4-triazine 4-oxide 113 with l-(dimethylamino)-l-ethoxyethylene leads to the... 

Highly electron-deficient 1,3,6,8-tetranitronaphthalene 443 was reported to react in ethanol with A -methyl phenylacetamidines, e.g. 444, to give the corresponding benzoquinoline derivatives, e.g. 446 (77JOC435). Though the reaction mechanism of this double nitro group displacement is not known, formation of intermediate 445 and its following cyclization is probably the most reasonable explanation (Scheme 70). 

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