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  #1  
Old 07-22-2012
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Drug What is inhibited by Methotrexate?

So now some really easy question for a change

A 58-year-old woman who has developed severe rheumatoid arthritis is placed on methotrexate therapy. During a follow-up visit, a blood test reveals moderately severe macrocytic anemia and hypersegmented neutrophils. Synthesis of which of the following is most likely inhibited in this patient?

a) DNA
b) Folate
c) Heme
d) Intrinsic factor
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Old 07-22-2012
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b) Folate or a) DNA

Actually methotrexate inhibits dihydrofolate reductase, enzyme that takes part in synthesis of tetrahydrofolate.

Folic acid is needed for the de novo synthesis of the nucleoside thymidine, required for dna synthesis. Also, folate is needed for purine base synthesis, so all purine synthesis will be inhibited. Methotrexate, therefore, inhibits the synthesis of DNA, RNA, thymidylate and proteins.

So folate synthesis is inhibited which inturn inhibits DNA synthesis.
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Old 07-22-2012
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Originally Posted by Casandra View Post
So now some really easy question for a change

A 58-year-old woman who has developed severe rheumatoid arthritis is placed on methotrexate therapy. During a follow-up visit, a blood test reveals moderately severe macrocytic anemia and hypersegmented neutrophils. Synthesis of which of the following is most likely inhibited in this patient?

a) DNA
b) Folate
c) Heme
d) Intrinsic factor
Its A DNA
methotrexate doesnt inhibit folate SYNTHESIS. it does inhibit synthesis of DHF and THF though
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  #4  
Old 07-23-2012
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Quote:
Originally Posted by Casandra View Post
So now some really easy question for a change

A 58-year-old woman who has developed severe rheumatoid arthritis is placed on methotrexate therapy. During a follow-up visit, a blood test reveals moderately severe macrocytic anemia and hypersegmented neutrophils. Synthesis of which of the following is most likely inhibited in this patient?

a) DNA
b) Folate
c) Heme
d) Intrinsic factor
Agree with the numbndumb opinion
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Old 07-23-2012
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Originally Posted by numbndumb View Post
Its A DNA
methotrexate doesnt inhibit folate SYNTHESIS. it does inhibit synthesis of DHF and THF though
agree..humans can't make folate.....they need them in the diet...i remem this line from a biochem book 5 years back
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Old 07-23-2012
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Default May be B

Methotrexate is thought to affect cancer and rheumatoid arthritis by two different pathways. For cancer, methotrexate allosterically inhibits dihydrofolate reductase (DHFR), an enzyme that participates in the tetrahydrofolate synthesis.[10] The affinity of methotrexate for DHFR is about one thousand-fold that of folate. DHFR catalyses the conversion of dihydrofolate to the active tetrahydrofolate. Folic acid is needed for the de novo synthesis of the nucleoside thymidine, required for DNA synthesis. Also, folate is needed for purine base synthesis, so all purine synthesis will be inhibited. Methotrexate, therefore, inhibits the synthesis of DNA, RNA, thymidylates, and proteins.
For the treatment of rheumatoid arthritis, inhibition of DHFR is not thought to be the main mechanism, but rather the inhibition of enzymes involved in purine metabolism, leading to accumulation of adenosine, or the inhibition of T cell activation and suppression of intercellular adhesion molecule expression by T cells.[11] In these cases, patients should supplement their diets with folate.

Came across this statement wikipedia.
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Old 07-23-2012
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A)...DNA
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Old 07-23-2012
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Folic acid must be converted to active THF forms before it can be of any use in the body. DHFR is the enzyme that is responsible for converting inactive folate into active THF forms.

Folic acid ---- ---DHF--------THF--------methylene THF ----------5 methyl THF

methylene THF leads to formation of pyrimidines and
also forms formyl THF (folinic acid) which leads to purine formation.

Methotrexate inhibits DHFR.
:sorry: sorry i shud hav said folate metabolism is inhibited by methotrexate .

YES, DNA WUD BE ANSWER.
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Old 07-27-2012
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Default correct answer :)

Correct answer is a) DNA

Methotrexate is a competitive inhibitor of dihydrofolate reductase. This blocks DNA synthesis and affects rapidly dividing cells, such as those involved in hematopoiesis.

Methotrexate, a folic acid analogue, does not block folate synthesis (polyglutamylation), although it also undergoes polyglutamylation.
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