Microsomes definition

These are the same quinones that are formed when 6-hydroxy-BP is oxidized by air or microsomes (19). However, there is no definitive evidence that 6-hydroxy-BP is an intermediate in their formation by PGH synthase. Among all of the stable metabolites of BP, the quinones are distinctive because, unlike phenols and dihydrodiols, they are not derived from arene oxides. Thus, arene oxides do not appear to be products of BP oxidation by PGH synthase (19,20). 

Applicable rate equations, with accompanying definitions of kinetic expressions, for the various activities of the partially purified rat liver microsomal enzyme at pH 6.0, derived on the basis of the mechanism in Fig. 4, are as follows (40) (to simplify notation, fc5 X [H20] is set =... 

The metabolism of atropine (227) by rat and guinea pig liver microsomes has been studied (197-199). French workers noted the formation of nora-tropine (229), apoatropine (233), and a phenolic metabolite formulated as the ortho-phenol 230 (197, 198) by liver microsomes from the rat, and they reported that hydrolysis of the ester function of 227 did not occur with enzymes from this source (197, 198). The structure of 229 was determined by TLC comparisons of the metabolite with an authentic sample and by correlation of the formation of the metabolite with the release of formaldehyde in the incubation mixture. The structure of 233 was deduced by TLC and UV spectral comparisons of isolated metabolite with authentic sample, and the phenol 230 was identified by TLC color reactions and by comparison with a phenolic sample obtained by Udenfried oxidation of atropine. In the absence of more definitive data on the phenolic products of this reaction, the structure 230 proposed for the phenolic metabolite of atropine... 

If metabolism in animal models is extensive or the generated metabolite(s) is shown to have toxic effects, in vitro metabolism studies using isolated P-450 isozymes, tissue homogenates containing the microsomal fraction, hepatocytes, and liver slices are commonly conducted to determine if the extent of metabolism and the metabolite profile is similar for animals and humans. The results from these in vitro metabolism comparison studies can be used to select the animal models for definitive development studies that have similar metabolism profiles to humans. 

Function tests of thyroid activity have little or no value in establishing the diagnosis of lymphocytic thyroiditis because of the wide spectrum of thyroid activity that may be seen in this condition. Thyroid function is likely to be normal, low normal, or subnormal, but on occasions increased function may be encountered. The diagnosis of this condition rests on a clinical suspicion of its existence, the presence of microsomal or thyroglobulin antibodies at high dilution with purposefully insensitive techniques (as discussed in Section 4.3). Where indicated, the definitive diagnosis is made by biopsy. 

Metabolic reaction phenotyping usually involves the use of enzyme specific chemical inhibitors in fully competent microsomal systems or recombinant enzyme systems individually expressing single enzymes. Once a drug candidate has entered the clinic, efforts will be made to perform a more definitive reaction phenotyping characterization as well as the consideration of clinical probe drug evaluations if patient risk is perceived. 

Only in brush-border membranes of some specialised cells and in erythrocyte membranes there seems to be an Mg-ATPase, which can be stimulated by anions, but only to a minor degree. Moreover, the properties of the enzyme in these membranes differ considerably from those of the activities in the microsomal and mitochondrial fractions of most other tissues. The anion sensitivity of the ATPase activity in the brush-border membranes of placenta and small intestine is a property of the alkaline phosphatase [37,41] and that in erythrocytes is part of the (Ca -b Mg )-ATPase activity [33,34]. Although this does not definitely exclude a role of the enzyme in anion transport, no valid arguments in favour of a role of this enzyme in anion or proton transport have been advanced. 

Thus the Type I 5 deiodinase activity in cerebral cortex, like that in the liver, requires an active sulfhydryl group, the carboxymethylation of which causes enzyme inactivation. In hypothyroid animals, most of the rT3 is deiodinated by the Type II pathway, since the Type I activity is reduced, and Type II activity increased several fold. Further studies with brain and brown adipose tissue microsomes have shown that the sensitivity of Type II activity to PTU is inversely related to the DTT concentration used during the assay, so that it is important to keep this factor in mind when assessing the sensitivity of a particular enzymatic activity to inhibition by this agent (15,16). Interested readers are referred to these references for a more thorough discussion of this complex area. While the two 5 deiodinase activities are quite distinct enzymatically, until such time as the protein sequences are determined, a definitive answer as to their structural similarities cannot be given. 

The effect of ethanol appears to result in an increase in porphyria according to data in the literature, but no definitive statement can as yet be made. A difference in the results is observed in acute or chronic intoxications, and conflicting statements have appeared as to the involvement of a microsomal oxygenase system. 

Apparently, the capacity of the desaturation enzyme system to convert saturated Into monounsaturated fatty acids depends on the amount of the terminal protein component and Its control Is mediated by protein synthesis and degradation (Oshlno and Sato, 1972). This fact could account for the liver s adaptability to different physiological conditions In which a definite microsomal desaturation activity Is required. Probably one of the best examples of this Is the response of the A9 desaturase enzyme to fasting and refeedlng. 

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