Tissue Microsomal

Corongiu, F.P., Lai, M. and Milia, A. (1983). Carbon tetrachloride, bromotrichloromethane and ethanol acute intoxication. New chemical evidence for lipid peroxidation in rat tissue microsomes. Biochem. J. 212, 625-631. 

St. John, L.C., Lunt, D.K., and Smith, S.B. 1991. Fatty acid elongation and desaturation enzyme activities of bovine liver and subcutaneous adipose tissue microsomes. J. Anim. Sci. 69,... 

The nitrosamines and nitrosamides are an important class of chemicals since a large number have been found to be carcinogenic. Nitrosamines require metabolic activation by target tissue microsomal mixed-function oxidases. 

Another approach with a set of human tissue microsomal samples is to measure the new reaction of interest in each and attempt correlation with rates of marker activities (for individual P450s). Lists are also published in this volume in Chapter 7 by Correia and elsewhere . 

The points raised in the Section 3.1, Inhibitors, apply to antibodies as well. Antibodies are used to inhibit activities in human liver (or other tissue) microsomes and are of several general types (a) polyclonal antibodies raised against purified animal P450s, (b) polyclonal antibodies raised against purified human P450s, (c) monoclonal antibodies raised against purified human P450s,... 

Usually activity results obtained with several of the major P450s are compared to eaeh other and to those obtained with tissue microsomes, in order to put the work in context. Ideally assays are done at several substrate concentrations and the parameters obtained. 

Tissue Microsomal P450 and Other Urinary Measures of Enzyme Induction... 

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 subject of P450 inhibition is also treated separately in this book (Chap. 5) [85], and this section is brief, focused on human P450s. A relatively extensive set of P450 inhibitors is now available, and many of these can be used in a diagnostic way for reaction phenotyping, i.e., identifying which P450s catalyze a newly discovered reaction in tissue microsomes (see Sect. 5). 

Kaul S, Krishnakantha TP. Influence of retinol deficiency and curcumin/turmeric feeding on tissue microsomal membrane lipid peroxidation and fatty acids in rats. Mol Cell Biochem 1997 175 43 8. 

Gel electrophoresis showed that rabbit Oryctolegus cuniculus) and, probably, rat (Ratius norvegiciis) livers contain variants of jS-D-glucuronidase corresponding to those in mouse Mus musculus) tissues.Microsomal and lysosomal fractions from rabbit liver differed only quantitatively in the j3-D-glucuronidases present. 

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