Activation, aggregation, and product inhibition of cobra venom phospholipase A2 and comparison with other phospholipases.
The kinetics of phospholipid hydrolysis by cobra venom phospholipase A2 were examined and compared to those of phospholipase A2 from porcine pancreas, Crotalus adamanteus (rattlesnake) venom, and bee venom. Only the enzyme from Naja naja naja (cobra) venom was found to be activated significantly by phosphorylcholine-containing compounds when hydrolyzing phosphatidylethanolamine. The cobra venom enzyme was also the only one in which these activators induced protein aggregation. The parallel specificity for activators and aggregators suggests that these two phenomena are linked. Product effects were also shown to vary between these four phospholipases. These effects manifest themselves in nonlinear time courses, in changes in steady state velocity, and in the differential effects of serum albumin on reaction rates. Different effects were even seen for the same enzyme when acting on different substrates. A model is presented to account for these observations; its main features are enzyme activation by an activator molecule, whose specificity depends on the enzyme, and an activator-induced aggregation of the enzyme.
D000818:Animals; D001514:Bee Venoms / Q000378:metabolism; D003435:Crotalid Venoms / Q000378:metabolism; D004546:Elapid Venoms / Q000378:metabolism*; D004789:Enzyme Activation; D007700:Kinetics; D046911:Macromolecular Substances; D010179:Pancreas / Q000201:enzymology; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D013045:Species Specificity; D013552:Swine
D001514:Bee Venoms; D003435:Crotalid Venoms; D004546:Elapid Venoms; D046911:Macromolecular Substances; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2