Metabolic oxidation products

The results presented above indicate that the previously unknown head-to-tail polymerization is the major reaction product of the iminium methide species. To investigate the generality of this reaction, we next studied a neutral ene-imine species shown in Scheme 7.9.48 As illustrated in this scheme, the generation of this reactive species requires quinone reduction followed by elimination of acetic acid. The ene-imine is structurally related to the methyleneindolenine reactive species that is a metabolic oxidation product of 3-methylindole (Scheme 7.9).57 59... 

An interesting biochemical method of manufacture is the utilization of bioengineered Pseudomonad plasmid (16) or Pseudomonas stut eri (17) in a culture medium to oxidize naphthalene or alkyl-substituted naphthalene. The metabolic oxidation products, unsubstituted or substituted salicylic acid,... 

Autoxidation of N-hydroxyamphetamine gives the nitroso-derivative which isomerizes to the corresponding oxime. A variety of AT-oxygenated products which might arise by oxidation, in vitro or in vivo, of 3,4-dimethoxyamphetamine and its V-alkyl derivatives have been prepared. A similar study has been carried out on the metabolic oxidation products of norephedrine. ... 

Finally, even the observation 14, 21) that the metabolic reactions likely to be related to the course of these ozone reactions are those of detoxification rather than of carcinogenic responsibility is not without exception—cf., e.g., the seven metabolic oxidation products of 5 (22) to the single ozonation product 24),... 

Vitamin A (retinol) (Fig. 7.12) and its metabolic oxidation products assume a critical physiological role in growth, development and differentiation of epithelial tissue, the maintenance of vision, and as well in spermatogenesis and the normal development of the placenta and the foetus. (allE)-Retinoic acid and (13Z)-retinoic acid are important medicaments for the treatment of acne and psoriasis the former has also demonstrated complete remission in most cases of acute promyelocytic leukemia (APL). 

All the phenalenones so far isolated from plants are derivatives of 9-phenyl-lH-phenalen-1-one (44). All the related compounds occurring with them may be regarded as metabolic oxidation products phenyl-naphthalides, phenylnaphthalic anhydrides, quinonemethides derived from oxa- and aza-phenalenones, derivatives of lH-naphtho[2,l,8- wia]-xanthen-l-one (45) and a phenalenone dimer. 

The way these carcinogens produce cancer is now fairly well understood. Unsubstituted PAHs are not very soluble, so to eliminate hydrocarbons, the body usually oxidizes them to render them more water soluble and then excretes them in urine. The metabolic oxidation products seem to be the real culprits in causing cancer. For example, one of the most potent carcinogens of this type is benzo[a]pyrene. Enzymatic oxidation converts it to the diol-epoxide shown below. The diol-epoxide reacts with cellular DNA, causing mutations... 

Dipyridamole exerts its effect by inhibition of platelet phosphodiesterase E5, increasing cyclic guanosine monophosphate and cyclic adenosine monophosphate (cAMP). By inhibiting its uptake and metabolism by erythrocytes, dipyridamole also increases the availability of adenosine within blood vessels, promoting inhibition of platelet aggregation and local vasodilatation. " Dipyridamole may also inhibit cAMP phosphodiesterase in platelets, which further increases cAMP levels and may enhance endothelial nitric oxide production, contributing to its antithrombotic effect. Existing trials of dipyridamole in stroke have focused on secondary prevention and will be discussed briefly. 

Bezalel L, Y Hadar, PP Fu, IP Freeman, CE Cerniglia (1996c) Initial oxidation products in the metabolism of pyrene, anthracene, tluorene, and dibenzothiophene by the white rot fungus Pleurotus ostreatus. Appl Environ Microbiol 62 2554-2559. 

Gauthier JJ, SC Rittenberg (1971) The metabolism of nicotinic acid II. 2,5-dihydroxypyridine oxidation, product formation, and oxygen 18 incorporation. J Biol Chem 246 3743-3748. 

Alcohol abuse is a major clinical problem in many countries and has been the subject of investigation for many years by those interested in determining the molecular basis of ethanol-induced liver dam e (see Lieber, 1990). These intensive and extended efforts have revealed much about the metabolism of ethanol in the liver and about the toxicity of its primary oxidative product, acetaldehyde. They have not, however, folly elucidated the molecular mechanisms that lead to the typical features of alcoholic liver injury steatosis, necrosis and eventually cirrhosis. 

The major metabolic pathway for hydrogen sulfide in the body is the oxidation of sulfide to sulfate, which is excreted in the urine (Beauchamp et al. 1984). The major oxidation product of sulfide is thiosulfate, which is then converted to sulfate the primary location for these reactions is in the liver (Bartholomew et al. 1980). 

Ni et al. [143] investigated the profile of the major metabolites of primaquine produced by in vitro liver microsomal metabolism, with silica gel thin-layer and high performance liquid chromatography analysis. Results indicated that the liver microsomal metabolism could simultaneously produce both 5-hydroxyprimaquine (quinoline ring oxidation product) and carboxyprimaquine (side-chain oxidative deamination product). However, the quantitative comparative study of microsomal metabolism showed that the production of 5-hydroxyprimaquine was far much higher than that of carboxyprimaquine. 

Alternatively, acrylonitrile is metabolized to 2-cyanoethylene oxide by the microsomal enzyme system. 2-Cyanoethylene oxide can react directly with tissue macromolecules or it can be further metabolized to oxidation products that release cyanide. Cyanide is converted to thiocyanate and excreted in the urine. 2-Cyanoethylene oxide is also conjugated with glutathione and metabolized to 2- hydroxyethylmercapturic acid which is excreted in the urine. 

Acrylonitrile is also metabolized to CO which is eliminated through the lungs. Carbon dioxide is produced when acrylonitrile is metabolized to ethylene oxide and degraded to oxidation products and cyanide via the epoxide hydratase pathways (Farooqui and Ahmed 1982 Young et al. 1977). 

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