Phospholipase A2 inactivation of microsomal 17 beta-hydroxysteroid oxidoreductase: rates of phospholipid hydrolysis and enzyme inactivation, effects of hydrolysis products and properties of the phospholipase A2-treated enzyme.
Exposure of guinea pig liver microsomes to phospholipase A2 resulted in the nearly complete loss of 17 beta-hydroxysteroid oxidoreductase (17 beta-HSD) activity, the time course of which correlated with phospholipid hydrolysis and lysolecithin formation. Lysolecithin and unsaturated fatty acids added to microsomes also inactivated 17 beta-HSD indicating that they may contribute to the inactivation by phospholipase A2. If exposure to lysolecithin and fatty acids was minimized by including serum albumin in the reaction mixture, phospholipids were rapidly hydrolyzed; but in this case the extent of 17 beta-HSD inactivation was less and the rate of loss was significantly slower. The data suggest that phospholipid hydrolysis per se results in a destabilization of 17 beta-HSD resulting in the subsequent activity loss. The inactivation of 17 beta-HSD by lysolecithin and fatty acids has not been reported previously and is suggestive of a possible control mechanism in vivo.
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D000818:Animals; D005227:Fatty Acids / Q000494:pharmacology; D006168:Guinea Pigs; D006868:Hydrolysis; D008244:Lysophosphatidylcholines / Q000096:biosynthesis / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology*; D009829:Oleic Acids / Q000494:pharmacology; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013739:Testosterone / Q000378:metabolism; D013997:Time Factors; D014357:Trypsin
D005227:Fatty Acids; D008244:Lysophosphatidylcholines; D009829:Oleic Acids; D010743:Phospholipids; D012710:Serum Albumin, Bovine; D013739:Testosterone; D015067:17-Hydroxysteroid Dehydrogenases; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D014357:Trypsin