Effect of a diazafluoranthen derivative on phospholipases. A study at the air-water interface.
AC-3579 (2-N-methylpiperazinomethyl-1,3-diazafluoranthen 1-oxide) produces in rat hepatocytes a hypertrophy of the endoplasmic reticulum. Two possibilities that can explain this phenomenon are (1) that AC-3579 inactivates the phospholipases, and (2) that an AC-3579-lipid interaction hinders the enzymic activity. To demonstrate these hypotheses, a physicochemical model of biological membrane, the lipid-water interface, has been used. Dipalmitoyl DL-alpha-phosphatidyl-choline was spread at the air-water interface, the enzymes (phospholipase A or phospholipase C) dissolved in the aqueous phase. The enzymic reaction was first studied with and without AC-3579 dissolved in the aqueous phase; no enzymic inactivation was observed. However an AC-3579-lipid complex completely inhibited the enzymic reaction in the case of phospholipase A. An explanation is given in terms of steric hindrance to the enzyme-substrate.
D000388:Air; D001372:Aza Compounds / Q000494:pharmacology; D001665:Binding Sites; D005449:Fluorenes / Q000494:pharmacology*; D007700:Kinetics; D010740:Phospholipases / Q000378:metabolism*; D010743:Phospholipids; D011312:Pressure; D011485:Protein Binding; D013499:Surface Properties; D014867:Water
D001372:Aza Compounds; D005449:Fluorenes; D010743:Phospholipids; D014867:Water; C006177:2-(4'-methylpiperazino-1-methyl)-1,3-diazafluoranthene 1-oxide; D010740:Phospholipases