So does this make any sense to you?

What I learned about Methotrexate while wating for Trick or Treaters and wondering why the college girls across the street only drive BMW's.


The CA name for methotrexate is: N[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic acid. The CA registry number is 59-05-2. Common synonyms: Mexate, Methylaminopterin, Emtexate, Metatrexan, Methopterin, MTX dihydrate, Folex, Folex PFS, Amethopetrin.
Methotrexate is an antineoplastic, an antirheumatic, a nucleic acid anti-metabolite (like 6-MP,above), and a "folic acid antagonist".
Hmm, folic acid, a necessary nutrient. Let's see, here's folic acid, let's compare:
folic acid
You can see that the nitrogen group has a CH3 on it and there is an OH group in the double ring instead of an NH2 group. Enough to make a difference in a biosynthesis scheme!
At two stages in the biosynthesis of purines (adenine and guanine) and at one stage in the synthesis of pyrimidines (thymine, cytosine, and uracil), one-carbon transfer reactions occur which require specific coenzymes.These coenzymes are synthesized in the cell from tetrahydrofolic acid. Tetrahydrofolic acid itself is synthesized in the cell from folic acid with the help of an enzyme, folic acid reductase. Methotrexate looks a lot like folic acid to the enzyme, so it binds to it thinking that it is folic acid. In fact, methotrexate looks so good to the enzyme that it binds to it quite strongly. All the folic acid reductase enzymes in the cell bind merrily to the methotrexate and ignore any folic acid they might see. Thus, DNA synthesis cannot proceed because the coenzymes needed for one-carbon transfer reactions are not produced from tetrahydrofolic acid because there is no tetrahydrofolic acid. Again, without DNA, no cell division.
Most of the parents of cancer kids have been told not to give folic acid supplements during chemo since it interferes with the action of the methotrexate.
Methotrexate has a general toxicity because it affects all rapidly dividing cells, such as those in the intestonal mucosa and prevents the production of tetrahydrofolate from folic acid in all tissues. Tetrahydrofolate is a necessary compound in many biosynthetic pathways, not just the synthesis of DNA. One of these is the synthesis of L-glutamate. One parent told us that her oncodoc recommended glutamic acid supplements, and that they helped her child immensely. Makes sense.
Also listed by the hospital: the possible adverse effects of this drug are mouth lesions in the form of painful patches on the lips, gums and mucosa of the mouth. These clear rapidly with stopping the drug. Along with mouth ulcers, there can also occur ulceration of other parts of the digestive tract with abdominal pain, vomiting and diarrhea. This drug can depress the bone marrow, which leads to a depression of white blood cells, platelets, and red blood cells.
Which means that they will be monitoring your child's CBC. With high doses of methotrexate, they will monitor fluid intake and urine output closely. Leucovorin is a medicine that may be prescribed. Leucovorin is an antianemic and an antidote for folic acid antagonists. Leucovorin is the active form of the B complex vitamin, folate. Another name for Leucovorin is folinic acid: the very name I found in a biochem text - it said that it could help alleviate the effects of methotrexate! "Leucovorin is used as an antidote to drugs that decrease levels of folic acid. Folic acid helps red and white blood cell formulation and the synthesis of hemoglobin. Some treatments require what is called leucovorin rescue, because the drug used to treat the cancer or other infection has had an adverse effect on folic acid levels. Leucovorin is used to reduce anemia in people taking dapsone, a preventive treatment for PCP. Leucovorin is also used in combination with chemotherapy such as methotrexate." (The words in "" are from the link on Leucovorin given above.)
References: Biochemistry texts, Web sites (various).
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