DISTRIBUTION OF ENZYMES INVOLVED IN METABOLISM OF POLYCYCLIC AROMATIC-HYDROCARBONS AMONG RAT-LIVER ENDOMEMBRANES AND PLASMA-MEMBRANES

  • 1 January 1980
    • journal article
    • research article
    • Vol. 21  (1) , 79-92
Abstract
The distribution of membrane-bound enzymes involved in the metabolism of polycyclic aromatic hydrocarbons was investigated in the same animals and in membrane fractions from rat liver. The purity of the fractions was controlled by EM morphometry, chemical analysis and determination of marker enzyme activities. Specific activities invariably were highest in ER [endoplasmic reticulum]. Epoxide hydrolase, monooxygenase, NADPH-cytochrome P-450 reductase, NADH-cytochrome b5 reductase and the concentrations of cytochromes P-450 and b5 were higher in smooth ER; by contrast, UDP-glucuronyltransferase (maximally activated) and membrane-associated glutathione-S-transferase activities were higher in rough ER. Nuclei and nuclear membranes showed high UDP-glucoronyltransferase activities (on a phospholipid basis 55-65% of that of rough ER) which did not exhibit latency. Plasma membrane, Golgi apparatus and nuclear membrane fractions had relatively high epoxide hydrolase and NADH-cytochrome b5 reductase activities and high concentrations of cytochromes b5 and P-450 (20-30% of levels present in smooth ER on a phospholipid basis). In whole mitochondria, glutathione-S-transferase, UDP-glucuronyltransferase and NADH-cytochrome b5 reductase activities were high, in contrast to exceedingly low (or absent) amounts of cytochrome P-450 and activities of cytochrome P-450 reductase, monooxygenase and epoxide hydrolase. Such differences of enzyme activities in the specific membranes might lead to differences in the intracellular distribution of reactive and inactive metabolites of aromatic hydrocarbons and thus may be important in diversification and regulation of metabolic pathways of carcinogenic compounds.