L-asparaginase Flashcards
L-asparagine is a nonessential amino acid synthesized by what process?
Where does the amine group come from?
transamination of l-aspartic acid
reaction catalyzed by l-asparagine synthetase
amine group from glutamine
What two things make cells sensitive to Lspar?
- Sensitive cells require asparagine as a constituent of protein
- Sensitive cells depend on asparagine as a NH2 donor group for glycine synthesis
MOA of Lspar?
Rapid/complete depletion of L-asparagine leads to inhibition of protein synthesis
What is the effect of Lspar on methotrexate?
L-asparaginase blocks methotrexate action, “rescues” from methotrexate toxicity
(inhibition of PS, prevention of entry into S phase)
Resistance to Lspar due to what? This is associated with what effect on the gene?
Upregulation of asparagine synthase causes resistance. Associated w HYPOMETHYLATION of asparagine synthetase gene
Name toxicities associated w Lspar
Decreased PS.
Pancreatitis
Hyperglycemia dt decreased insulin synthesis
Decreased procoagulant and anticoag clotting factors (2,5,7,9,10,AT3)
Serum sickness
HS reactions (patients usually have IgE and IgG abys to l-asp in serum…but lots patients have these w/o HS)
Cerebral dysfunction (hyperammonemia?)
Why should vinc be given before Lspar?
How much before?
L-asparaginase may reduce hepatic clearance of vincas (esp VCR), which may result in increased toxicity•
Give VCR 12-24h before L-spar
What is the effect of Lspar on methotrexate?
How does this relate to the cell cycle?
Asparaginase blocks methotrexate action, “rescues” from methotrexate toxicity
♣ Inhibition of PS, prevention of entry into S phase of cell cycle