Animals conjugates

In most normal adult animals, conjugation of bilirubin with various sugars probably represents the major mechanism for its transformation (Fig. 1). The reaction products are eliminated from the organism by excretion into the bile. Glucuronyl transfer has been investigated in... 

Carotenoids are natural pigments characterized by a tail to tail linkage between two C20 units and an extended conjugated system of double bonds They are the most widely dis tributed of the substances that give color to our world and occur m flowers fruits plants insects and animals It has been estimated that biosynthesis from acetate produces approximately a hundred million tons of carotenoids per year The most familiar carotenoids are lycopene and (3 carotene pigments found m numerous plants and easily isolable from npe tomatoes and carrots respectively... 

As a low molecular weight compound DAS is not significantly immunogenic, ie, it is a hapten and thus requires conjugation to a suitable antigenic carrier in order to eUcit a successfiil antibody response in animals. DAS treated with succinic anhydride results in the D AS—hemisuccinate (DAS—HMS) shown. 

Standardization and Testing". RequHemeats are geaerally specified within Hceases Hi the United States, and include a variety of Hi-process tests to assess purity, safety, and potency of the iadividual components and potency and safety of the final product. Potency is standardized by determining the size of the conjugate and the quantitative amount of saccharide that is bound to the carrier protein. General safety and immunogenicity is assessed Hi animals. 

Human sensitization studies were negative at 10% solution (47). Undiluted benzyl alcohol produces moderate dermal irritation in guinea pigs and mild dermal irritation in rabbits (48,49). Severe eye irritation was noted in a rabbit study (50). Acute oral rat LD q values were reported between 1.23 and 3.10 g/kg (50—52). A dermal rabbit LD q value of 2.0 g/kg has been reported (49). Rats died after 2 h when exposed to a 200-ppm vapor concentration (53). Benzyl alcohol is readily oxidized in animals and humans to benzoic acid [65-85-0] which is then conjugated with glycine [56-40-6], and rapidly eliminated in the urine as hippuric acid [495-69-2] (54). 

The much simpler steroid, 253, was fortuitously found to fulfill this role when injected into animals. Its lack of oral activity was overcome by incorporation of the 7a-thioacetate group. Reaction of the ethisterone intermediate, 77b, with a large excess of an organomagnesium halide leads to the corresponding acetylide salt carbonation with CO2 affords the carboxyllic acid, 251. This is then hydrogenated and the hydroxy acid cy-clized to the spirolactone. Oppenauer oxidation followed by treatment with chloranil affords the 4,6-dehydro-3-ketone (254). Conjugate addition of thiolacetic acid completes the synthesis of spironolactone (255), an orally active aldosterone antagonist. ... 

N-Aminobenzoxazolin-2-one (4), which was readily prepared by animation of benzoxazolin-2-one with hydroxylamine-O-sulfonic acid, is also a useful nitrene precursor (Scheme 2.2). Oxidation of 4 with lead(iv) acetate in the presence of a conjugated diene resulted in exclusive 1,2-addition of nitrene 5, to yield vinylazir-idine (6) in 71 % yield [6]. The formation of vinylaziridines through 1,2-additions of methoxycarbonylnitrene (2) or amino nitrene 5 contrasts with the claimed 1,4-ad-dition of nitrene itself to butadiene [7]. Since the reaction proceeded stereospecif-ically even at high dilution, the nitrene 5 appears to be generated in a resonance-stabilized singlet state, which is probably the ground state [8]. 

Residues of PCBs in animal tissues include not only the original congeners themselves, but also hydroxy metabolites that bind to cellular proteins, for example, transthyretin (TTR Klasson-Wehler et al. 1992 Brouwer et al. 1990 Fans et al. 1993). Small residues are also found of methyl-sulfonyl metabolites of certain PCBs (Bakke et al. 1982, 1983). These appear to originate from the formation of glutathione conjugates of primary epoxide metabolites, thus providing further evidence of the existence of epoxide intermediates. Further biotransformation, including methylation, yields methyl-sulfonyl products that are relatively nonpolar and persistent. 

In terrestrial animals, the excreted products of PAHs are mainly conjugates formed from oxidative metabolites. These include glutathione conjugates of epoxides, and sulfate and glucuronide conjugates of phenols and diols. 

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