L-asparaginase Flashcards

1
Q

L-asparagine is a nonessential amino acid synthesized by what process?

Where does the amine group come from?

A

transamination of l-aspartic acid

reaction catalyzed by l-asparagine synthetase

amine group from glutamine

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2
Q

What two things make cells sensitive to Lspar?

A
  1. Sensitive cells require asparagine as a constituent of protein
  2. Sensitive cells depend on asparagine as a NH2 donor group for glycine synthesis
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3
Q

MOA of Lspar?

A

Rapid/complete depletion of L-asparagine leads to inhibition of protein synthesis

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4
Q

What is the effect of Lspar on methotrexate?

A

L-asparaginase blocks methotrexate action, “rescues” from methotrexate toxicity

(inhibition of PS, prevention of entry into S phase)

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5
Q

Resistance to Lspar due to what? This is associated with what effect on the gene?

A

Upregulation of asparagine synthase causes resistance. Associated w HYPOMETHYLATION of asparagine synthetase gene

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6
Q

Name toxicities associated w Lspar

A

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?)

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7
Q

Why should vinc be given before Lspar?

How much before?

A

L-asparaginase may reduce hepatic clearance of vincas (esp VCR), which may result in increased toxicity•

Give VCR 12-24h before L-spar

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8
Q

What is the effect of Lspar on methotrexate?

How does this relate to the cell cycle?

A

Asparaginase blocks methotrexate action, “rescues” from methotrexate toxicity
♣ Inhibition of PS, prevention of entry into S phase of cell cycle

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