Enzymes cytochrome patterns, microsomal

Thus, it can be easily theorized that the shift seen in the microsomal enzyme and cytochrome patterns caused by dietary fat and antioxidants may be related to the inhibitory and enhancing effects of these compounds on chemical carcinogenesis. Further studies are indicated to look at specific carcinogen metabolites produced by the drug metabolizing systems of animals consuming the various diets, and to attempt to correlate the corresponding cytochrome and enzyme levels with these metabolites and ultimately with resultant tumor incidences and tumor numbers. 

Hepatitis describes infiltration of the hepatic tissue by mononuclear cells, which may or may not be associated with hepatocellular changes. There are also different patterns of cellular injury, such as those affecting the hepatocellular organelles— particularly, the microsomes, peroxisomes, and mitochondria. When hepatocellular injury occurs, the aminotransferases are probably the most useful markers, and they may be supplemented by measurements of other plasma enzymes—ALP, GLDH, and plasma bilirubin (see the following sections on laboratory investigations). Several markers of cellular function require tissues for the measurements of altered function (e.g., microsomal cytochrome P450 measurements). 

These correlations between vitro alkylation and Jjn vivo alkylation and toxicity suggest that differences in patterns of tissue-specific toxicity of IPO are due, at least in part, to differences in the ability of target tissues to activate the toxin (i.e. activities are either present or absent in potential target tissues). There may be multiple reasons for these differences. For example, although a cytochrome P-450 appears to be required for the metabolic activation of IPO, there is not a good correlation between total microsomal content of this enzyme and the capacity of the microsomes to metabolize IP0(12,13,14). For instance, rat kidney microsome preparations... 

These findings suggest that liver microsomes contain at least two different cytochrome P-450 s each of which is present as two interconvertible forms. It is still possible that microsomes contain other fimctionally different cytochromes which have thus far not been identified. The concept of a number of fimctionally different cytochrome P-450 in liver microsomes could account for the marked variations in the pattern of drug metabolism found in various animal species or after various treatments. At the present time, however, it seems likely that any form of cytochrome P-450 may catalyse a number of different reactions and that any of the reactions may be catalysed by a number of different forms of cytochrome P-450. For this reason the various enzymes should not be referred to simply as demethyl-ases, hydroxylases, deaminases, etc., without refo-ring to the substrate. 

The elaboration of androgen in male rats triggers an increase in microsomal enzyme activity which can be abolished or prevented by castration. However, it should not be inferred that all hepatic microsomal enzymes reach their peak activities concomitant with sexual maturation. Indeed, glucuronyl transferase activity toward p-nitrophenol is maximal in new-bom rats and tends to decline thereafter whereas transferase activi towards bilirubin or phenolphthalein is very low at birth and progressively increases to adult levels. Similarly, NADPH and cytochrome P-4S0-dependent microsomal enzymes have developmental patterns unrelated to each other and to cytochrome P-4S0. For example, aniline hydroxylase in male rats reaches peak activity at 2 weeks of age which is 2 4 weeks prior to sexual maturation, whereas ethylmorphine N-demethylase activity does not become maximal until about 4 5 weeks of age. During the first S weeks of life, these activities increase by about 100% but cytochrome P-4S0 changes only insignificantly. 

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