Metabolic change as an early step in excretion

Although this example shows that e.r. is not the sole site of metabolic degradation, this organelle is by far the most versatile. It can be separated from liver by differential ultracentrifugation and is similarly freed from the neigh- 

Cytochrome P-448, whose normal function may lie in the oxidative biosynthesis of steroids, is induced further by some potential carcinogens such as 2-acetamidofluorene, 3-methylcholanthrene, and cigarette smoke. This cytochrome has a selective binding site that attacks hindered areas inaccessible to P-450. It converts some potential carcinogens (such as benzo[ z]pyrene and 1,2,5,6-dibenzanthracene) to ultimate carcinogens (Sect. 13.5). P-448 predominates over P-450 in malignant tissues (loannides, Lum and Parke, 1983). For more on P-450, see Schenkman and Kupfer (1982). 

The following typical oxidative processes are performed by the microsomal enzymes there is at least one enzyme for each process  

The ej. can perform yet other reactions such as dechlorination of chlorinated aliphatic hydrocarbons. This can be either oxidative, in which case the products are ketones, or reductive, as with carbon tetrachloride which produces the highly toxic free radical CH2 (Salmon, Jones and Mackrodt, 1981). Moreover, the ej. carry at least two reducing enzymes a nitro-reductase and an azo-reductase, both of which produce primary amines. 

Metabolic alteration of foreign substances has often been called detoxification , but examples are known where the product of an e.r. enzyme is more 

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Metabolic change as an early step in excretion. Synergism and antagonism. 79... 

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