Venom Toxins: Plausible Evolution from Digestive Enzymes

Some hydrolytic enzymes are common to the pancreas, the mammaliansalivary glands and the snake venom glands. Phospholipase A,which is found in elapid and viperid venoms and in the mammalianpancreas, shows 29 common amino acid residues out of 118–125positions. Presynaptic neurotoxins and other venom toxins areusually composed of 2–3 units or subumts,one of whichis a phospholipase. The Vipera palaestinae two-component toxinretains its lethality when the enzyme is replaced by heterologousvenom phospholipases, but not by the pig pancreatic enzyme.This toxin is neutralized by a factor found in the blood serumof snakes, which binds to the phospholipase and inhibits itsactivity. The blood serum of snakes also neutralizes hemorrhaginsand inhibits the protease activity of the venom. It is hypothesizedthat the developing venom glands first produced enzymes thatwere already secreted by the pancreas and against which inhibitorswere present in the blood. These inhibitors facilitated theevolution of enzyme-based toxins by neutralizing any damagingsubstances that might have escaped from the venom glands.