Professor Tipton, being an avid hunter, was stalking the woods for morels. He sa

Question

Professor Tipton, being an avid hunter, was stalking the woods for morels. He saw a giant morel next to a fallen tree. When he reached down to get it a small timber rattler bit his hand. By time he got back to the car, the bite mark was swollen and extremely painful. Being a card-carrying enzymologist, he knew that many snake venoms contain phospholipases A2. a) Explain why the snake bite caused rapid pain and inflammation (a biochemical explanation; it has nothing to do with Dr. Tipton’s pain tolerance). b) Based on your biochemical understanding of the mechanism of the pain (Chapter 10), suggest a possible treatment (no amputations please). c) If too much phospholipase A2 enters the bloodstream, the significant accumulation of one of the products of the reaction acts as a powerful detergent, causing the lysis of red blood cells and potential death. What is this dangerous product and what makes it such a good detergent?

(8 pts) Melittin is a 26 amino acid helical peptide (GIGAVLKVLTTGLPALISWIKRKRQQ) that is the major component of bee venom and is responsible for cell death by disrupting the plasma membrane. Develop a logical explanation of how this peptide could facilitate membrane disruption.

Explanation / Answer

a)

PLA2 are commonly found in mammalian tissues as well as insect and snake venom.[2] Venom from both snakes and insects is largely composed of melittin, which is a stimulant of PLA2. Due to the increased presence and activity of PLA2 resulting from a snake or insect bite, arachidonic acid is released from the phospholipid membrane disproportionately. As a result, inflammation and pain occur at the site.

b)

Certain steroids such as prednisone inhibit the action of phospholipase A2, the enzyme
that releases the fatty acid arachidonate from the C-2 position of some membrane
glycerophospholipids. Arachidonate is converted to a variety of eicosanoids, some of
which cause inflammation and pain.

c) The venom of yellow jackets contains many toxic substances like phospholipases, hyaluronidases, and a toxic protein known as antigen 5 (8). These toxins can damage red blood cells and myocyte membranes causing hemolysis and rhabdomyolysis (1, 3, 8). The resultant excess of both hemoglobin and myoglobin pigments leads to acute tubular necrosis and renal failure. A direct toxic effect of the venom on renal tubular cells has also been proposed (1). Our patient had both intravascular hemolysis and elevated serum creatinine phosphokinase-MM isoenzyme levels suggesting rhabdomyolysis.Phospholipase A2 causes hemolysis by lysing the phospholipid cell membranes of red blood cells.

Melittin exemplifies this large class of membrane-active peptides that manifest membrane-disrupting activity when incorporated into traditional bilayer delivery systems (i.e., liposomes).
It is a very nonspecific cytolytic peptide that attacks all lipid membranes, leading to significant toxicity when injected i.v.; the basis of its action is a physical and chemical disruption of membrane structure, resulting in profound compromise of the cell permeability barrier.
Melittin forms ion channels which span membrane bilayers through the tetrameric association of melittin monomers; the channels are more permeable to anions than to cations, probably due to the accumulation of positive charges on the C-terminal region.

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