17.5.07

L-Asparaginase (Elspar) - Sounds like an asparagus-based cream cheese spread

  • anticancer drug used in combination with other such drugs to treat certain leukemias, particularly childhood acute lymphoblastic leukemia (ALL)
  • is an enzyme derived from bacteria that breaks down L-asparagine, a non-essential amino acid that certain leukemic cells are incapable of making enough of for themselves
    • these cells don't have enough L-asparagine synthetase, the enzyme required to, you know, synthesize the stuff
    • these cells are vulnerable to a decrease in the extracellular supply of L-asparagine, which is exactly what the drug causes - since proteins are made up of amino acids, the cells experience inhibition of protein synthesis resulting in their utter and total destruction
  • resistance appears as increased expression of the gene encoding L-asparagine synthetase, which enables the cells to synthesize enough L-asparagine on their own (boo!)
  • hypersensitivity (allergic) reactions are common since it is a bacterial enzyme and so a foreign protein that the immune system takes issue with
  • some normal cells are also vulnerable to a decrease in the extracellular supply of L-asparagine and so experience inhibition of protein synthesis following administration of the drug - this can lead to, among other things, decreased production of anticoagulant and thrombolytic factors (normally required to prevent the formation of blood clots or bust them apart, respectively) and possible thrombosis (clotting) of major vessels (the result being things like deep vein thrombosis, heart attack, and stroke)
Kalant H, Grant D, and Mitchell J. Principles of Medical Pharmacology 7th ed. Toronto: Saunders Canada, 2006.

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