Acetylation rate

Acetylation rates have also been studied by Centola37 who treated natural and mercerized ramie fibers for varying times with acetic anhydride and sodium acetate and examined the reaction products chemically and by X-ray diffraction. The reagent was considered to penetrate into the interior of fibers. A heterogeneous micellar reaction was believed to occur that converted a semi-permeable elastic membrane around the micelles into the triacetate. The rate of acetylation of mercerized ramie was observed to be faster than that of unmercerized fiber. Centola concluded that about 40 % of the cellulose in native ramie is amorphous and acetylates rapidly. 

The relative rates of acetylation in competition experiments in the [m.n]paracyclophane series 38> may be interpreted in terms of trans-annular electronic and steric effects. If the rate of acetylation of [6.6]para-cyclophane [(7), m =n =6] is is taken as one, the relative acetylation rates of the [4.4]-, [4.3]-, and [2.2]paracyclophanes are 1.6, 11, and >48, respectively. As the aromatic rings come closer together, the rate of entry of the first acetyl group into the nucleus increases, while that of the second acetyl group decreases. Both effects clearly indicate that the positive. partial charge can be distributed over both benzene rings in the monoacetylation transition state (64). 

Susceptibility to bladder cancer in humans has been linked to the slow acetylator phenotype of the polymorphic NAT2 AT-acetyltrans-ferase gene. In a study from China, a 25-fold increase in bladder cancer incidence and a 17-fold increase in bladder cancer mortality were determined in 1972 benzidine-exposed workers. In the Asian population the slow acetylator phenotype occurs significantly less often than in Caucasian populations, but an association between those who contracted bladder cancer and phenotype has yet to be determined for this group. Other, more recent data have suggested that the acetylation rate may not be an important risk factor for developing bladder cancer. ... 

The extent to which a sulfonamide is acetylated depends upon the drug administered and the animal species. Acetylsulfathiazole is the principal metabolite found in the urine of cattle, sheep, and swine after enteral or parenteral administration of sulfathiazole. However, sheep can acetylate only 10% of the dose, while cattle can acetylate 32%, and swine 39%. When sulfamethazine was administered intravenously or orally to cattle, the animals eliminated 11% or 25% of the dose, respectively, in urine as N" -acetylsulfamethazine. The increased acetylation that occurred following tlie oral administration may be related to the increased exposure of sulfamethazine to liver enzymes following its absorption into the portal circulation. The acetylation rate may also be affected by the health status of an animal. Tims, cows suffering from ketosis in cows acetylate sulfonamides at much lower extent. 

It reveals the difficulties of testing for this type of reaction in experimental animals when the various predisposing factors may not be present. However, the LE syndrome does occur in certain strains of mice and acetylation rates do vary between strains of laboratory animals. Using such specific models might therefore allow improved prediction. 

The initial rate of 2-MN acetylation depends on the framework Si/Al ratio of the zeolite catalyst.[27] For a series of dealuminated BEA samples (by treatment with hydrochloric acid or with ammonium hexafluorosilicate), the acetylation rate passes through a maximum for a number of framework A1 atoms per unit cell (/VA() between 1.5 and 2.0 (Si/Al ratio between 30 and 40). The activity of the protonic sites (i.e. the TOF) increases significantly with Si/Al from 420 h 1 for Si/Al = 15 to 2650 h 1 for Si/Al = 90. It should be noted that similar TOF values could be expected from the next nearest neighbour (NNN) model. Indeed all the framework A1 atoms of the zeolite (hence all the corresponding protonic acid sites) are isolated for Si/Al ratio 10.5. Therefore the acid strength of the protonic sites is then maximal as well as their activity.[57,58] This was furthermore found for m-xylcnc isomerization over the same series of BEA zeolites.1271 This increase in TOF for... 

MN acetylation is most likely related to the high polarity and bulkiness of the products with limitations in the reaction rate by product desorption. Dealumination would have a positive effect on the acetylation rate because of the decrease in the zeolite hydrophilicity and of the increase in the rate of diffusion of the bulky products owing to elimination of extra-framework A1 species. Curiously, in anisole acetylation, the Si/Al ratio of the HBEA zeolite had practically no effect on the reaction rate. However it is worth noting that most of the tested samples had Si/Al ratios between 11 and 30. Like for 2-MN acetylation,[28,32] the performance of HBEA zeolites in anisole acetylation depends on their crystallite size.[17] This was shown by comparing the activities of samples with large size (0.1-0.4 pm) and of a nanosize sample (0.01-0.02 pm) prepared within the pores of a carbon black matrix. The superior performance of the nanosize sample was ascribed to a decrease in diffusional constraints limiting the desorption of the bulky and polar p-methoxyacetophenone product from the BEA micropores. 

The solvents used to solubilize 2-MN reactant and AMN products were shown to have a large effect on the reaction rate and selectivity.1251 Thus, the rate of acetylation was maximum in 1,2-dichloromethane, higher than in 1-methylnaphtha-lene, which is less polar, and in nitrobenzene and sulfolane, which are more polar. The polarity referred to here relates to the polarity parameter ET proposed by Dimroth and Reichardt.159,601 This change in acetylation rate can be explained by two opposite effects of the solvent polarity 1251... 

Figure 2.30. Metabolism of isoniazid. a Acetylation, b Hydrolysis of the acetyl conjugate leads to liver toxicity, c Distribution of acetylation rates in the population.

Table I gives the results of calculations of the acetylation rate constants based on Equations 22, 28, 31, and 34. Acetosulfamine and sulfadi-methoxine are omitted in the correlations of 12 compounds for which the substituent parameters are known since preliminary calculations showed that the data for these two did not fit well in each case. Different routes for the metabolism of these two compounds might be operative. In fact, for sulfadimethoxine, glucuronide formation has been shown to occur to a considerable extent, and this can not be neglected as compared with the acetylation at liver in rats (6) and humans (II). We expected that acetosulfamine would behave as an acetyl donor as well as the acetyl acceptor. Thus, the N-4-acetyl group of N-4-acetylacetosulfamine might result not only from acetyl-CoA but also from the N-l-acetyl group of another acetosulfamine molecule.

According to these data, an increase in the content of altropyranose units in the macromolecule of mixed polysaccharide (III) leads to a sharp fall in its acetylation rate as compared with cellulose. Similar results have been obtained for the nitration reaction of (III). An analogous relationship is observed for mixed polysaccharide (IV) upon acetylation preceded by the activation of the starting material. 

Mitchell JR, Long MW, Thorgeirsson UP, Jollow DJ. Acetylation rates and monthly liver function tests during one year of isoniazid preventive therapy. 

Concerning the compounds adsorbed on the active sites of the catalyst that can decrease the acetylation rate, two classes of products have been recognized after zeolite mineralization. Monoacetylated products are observed from anisole, whereas comparable amounts of mono- and diacetylated products are observed from 2-methoxynaphthalene (2-MN), meta-xylene, and 2-methylnaphthalene essentially, diacetylated products are observed from toluene. This behavior is related to the difference in polarity between the substrates and the acetylated products, the... 

Inheritance of certain metabolic phenotypes is also associated with cancer risk. Rapid hydroxylation of debrisoquine, a medication originally used to treat hypertension, is associated with increased risk of lung cancer (24). Similarly, individuals that have a slow acetylation rate for caffeine are at increased risk of bladder cancer (25-271. while those with a rapid acetylation phenotype are more susceptible to colon cancer (25). The combined effect of these phenotypes with environmental exposures further increases cancer risk. 

Differences in acetylation rates have also been shown to occur with procainamide, but unlike hydralazine, the conclusion is less clear. Henningsen et al. (1975) carried out a prospective study of 42 patients on long-term procainamide treatment they were able to show that 12 patients (29%) developed a classic drug-induced lupus syndrome. The acetylation status was determined on 11 of these 12 patients, 8 proved to be slow and 3 fast acetylation. The authors concluded that... 

The reactivity of polymers also can be changed by shear, as discussed in Section A of this chapter, as a consequence of bond angle deformation. For example, vibromilling enhances the acetylation rate of cellulose [1, 2] and its reactivity to xanthation [3]. Other examples (hydrolysis, methanolysis, dehydrochlorination, or dehydrocyanuration) have been quoted in Section A. The changes in chemistry are most often evinced and utilized as changes in mechanical, rheological and solubility characteristics. 

Differences in the amount of postsynthetic modifications (acetylation and phosphorylation) were also observed at various stages of development. The imago demonstrated a higher level of such modification. There are interspecies differences in the distribution of histones for both developmental stages. The acetylation rate of H3 may be exceptional in D. virilis because it is at a relatively low level at every stage of development (Holmgren et al., 1976). 

Acetylation of histones reduces their ability to inhibit RNA synthesis in vitro (Allfrey et al., 1964). The acetylation rate and concentration of acetyl-group histones are higher in transcriptionally active chromatin. Deacetylation of histones, at the same time, does not slow down. The rate of histone acetylation increases in types of cell where RNA synthesis is stimulated, i.e., spleen cells treated with eryth-ropoetin, liver cells under the influence of cortisol, milk gland cells treated with insulin, etc. (Allfrey et al, 1972). Inhibition of nuclear activity is accompanied by the deacetylation of histones. 

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