say: ell-ess-PAIR-uh-gin-aze
No, you don't get a chemical structure for this one! This molecule is a tetrameric protein, with a molecular weight of >140,000. Wouldn't fit on the page in time for you to download. In comparison, 6-MP has a molecular weight of 152, so it's about a thousand times bigger! The exact molecular structure of large proteins is often not known. The CA registry number is 9015-68-3. Additional names include L-asparagine amidohydrolase, L-asnase, Crasnitin, Elspar, kidrolase, Leunase, Asparaginase; Colaspase; Crasnitin; EC 2; Leucogen. It is an antineoplastic.
Asparaginase is a protein, and it is an enzyme. Enzymes catalyze, or facilitate, chemical reactions in a cell. They have many different modes of action, which I will not go into here (whew!). But, how about a mini-review on proteins?
Proteins are the work-horses of the cell, just as DNA is the director and RNAs are the messengers. Proteins serve as enzymes, antibodies, structural elements, transport devices, and metabolic regulators. Proteins are made up of amino acid building blocks. Amino acids include: glycine, alanine, leucine, isoleucine, serine, threonine, aspartic acid, asparagine, glutamic acid, glutamine, lysine, hydroxylysine, histidine, arginine, phenylalanine, tyrosine, tryptophan, thyroxine, cysteine, cystine, methionine, proline, and hydroxyproline. Each amino acid is a molecule with an amine group at one end, -NH2, and a carboxylic acid group at the other end, -CO2, and various other carbon-sulfur-hydrogen-oxygen-nitrogen mixes in between. The two "ends" of the molecules sort of snap together to make an amide bond, -NH-CO-, and they build long chains, or polymers, like a pop bead necklace. The order of the amino acids is VERY IMPORTANT to the functionality of an enzyme. The order of amino acids in an enzyme is directed by mRNA that is in turn directed by DNA.
Asparaginase catalyzes the hydrolysis of asparagine to aspartic acid. Tumor cells, especially ALL cells, have low levels of asparagine synthetase, the enzyme (remember the -ase?) that catalyzes the synthesis of asparagine. Therefore, tumor cells require an external source of asparagine. Asparaginase serves to destroy all the asparagine that does manage to get synthesized in a tumor cell or that comes in from other sources, thus, the cells die because they do not have the asparagine needed to build proteins, thus, no enzymes, structural elements . . . all the activities in the above paragraph . . . and the tumor cell dies.
<Okay now guys . . . what do you NOT run to the health food store to feed the chemo kids? That's right, asparagine!>
Asparaginase does not occur naturally in humans, but it is found in bacteria, plants, and many animals, including guinea pigs. Asparaginase for chemotherapy is usually isolated from cultures of E. Coli bacteria. Another form is isolated from Erwinia; the Erwinia form has both advantages (can cause less of an allergic reaction) and disadvantages (might not be as active, is sometimes difficult to obtain from the manufacturer). Another common form is PEG-asparaginase; this is the E-coli enzyme stabilized with polyethylene glycol (PEG). PEG asparaginase might be more effective than the plain asparaginase. PEG asparaginase has a longer "half life" in the body and thus does not have to be given on the Mon-Wed-Fri schedule used for E. Coli asparaginase (fewer doses are necessary). PEG asparaginase also causes fewer allergic reactions. All three forms of asparaginase were used and compared in ALL trials in the 1990s and early 2000s.
Asparaginase was "discovered" about 35 years ago. They found that guinea pig serum (Kidd) suppressed the growth of lymphosarcomas in mice; asparaginase was later shown to be the active factor. It's not like the scientists knew that tumor cells has a low level of asparagine synthetase and designed the asparaginase treatment, rather, they found the treatment and worked backwards to find out why it worked.
An interesting discussion of asparaginase can be found at Worthington.
In our experience, asparaginase has always been injected intramuscular. It's kind of scary to see: they put the needle perpendicular to the large muscle in the thigh, pretty deep. Thank goodness for Emla.
Many of the side effects of asparaginase are due to the fact that is a protein - its most important side effect is the possible occurrence of a severe (and occasionally fatal) allergic reaction. Therefore, the first time the drug is given, the patient will be monitored very carefully for several hours for:
If they do happen, the docs will be ready with medications to reverse these effects. If these allergic reactions do not happen after the first dose, later doses will require only a 30 minute wait in the docs office before they release you. Other toxic effects that the docs will be watching for can be:
These effects are due to a temporary effect on the pancreas, that in rare circumstances can produce a reversible diabetes-like picture.
Side effects that usually do not require medical attention are:
Do not have any immunizations during or soon after administration of this drug. Make sure you drink plenty of water while taking this drug.
For the sheet they gave us at the hospital, press here.