Microsomes phosphodiesterase

Davies DB, Holub BJ. 1983. Comparative effects of organophosphorus insecticides on the activities of acetylcholinesterase, diacylglycerol kinase, and phosphatidylinositol phosphodiesterase in rat brain microsomes. Pesti Biochem Physiol 20 92-99. 

Another enzyme found to be present in increased amounts in psoriatic serum as compared to normal is a phosphodiesterase studied by Zaruba et al. (Z3). Again this enzyme is found in elevated amounts in psoriatic epidermis and presumably the increase of enzyme in the serum is the result of leakage from the epidermis. With this enzyme, which is presumably bound to microsomes and mitochondria, it is a little more difficult to understand exactly how it leaks out of the cell. 

Sugiura T, Kondo S, Sukagawa A, Tonegawa T, Nakane S, Yamashita A, Ishima Y, Waku K (1996b) Transacylase-mediated and phosphodiesterase-mediated synthesis of N-arachidonoylethanolamine, an endogenous cannabinoid-receptor ligand, in rat brain microsomes. Comparison with synthesis from free arachidonic acid and ethanolamine. Eur J Biochem 240 53-62... 

All three phosphodiesterase inhibitors are hepatically catabo-lized by the cytochrome P450 3A4 microsomal isoenzyme as well as by other P450 isoenzymes (minor routes) and/or other hepatic enzymes. The drugs and their metabolites (some of which are active) are excreted primarily in the feces, but also in the urine to varying degrees (see Table 84-4). 

The hepatic metabolism of all three phosphodiesterase inhibitors can be inhibited by cytochrome P450 hepatic microsomal enzyme... 

FIGURE 7.3 Comparison of theiV-acyl moieties of iV-acylethanolamines (A), N-acyl moieties of N-acyl PEs (B), fatty acids esterified at the 1-position of phosphatidylcholine (C) and free fatty acids (D) in rat brain. Values are the means of four to six determinations. (From Sugiura, T., Kondo, S., Sukagawa, A., Tonegawa, T., Nakane, S., Yamashita, A., Ishima, Y, and Waku, K. (1996) Transacylase-mediated and phosphodiesterase-mediated synthesis of iV-arachidonoylethanolamine, an endogenous cannabinoid receptor ligand, in rat brain microsomes. Comparison with synthesis from free arachidonic acid and ethanolamine, European Journal of Biochemistry 240 53-62. With permission.)... 

With regard to phosphodiesterase (Butcher and Sutherland, 1962), brain has the highest activity (Drummond and Perrott-Yee, 1961) and the enzyme is distributed between soluble and particulate fractions obtained by ultracentrifugation of brain homogenates. The diesterase is located inside nerve endings which enrich the microsomal fraction (Cheung and Salganicoff, 1967). 

---