Methotrexate in rheumatoid arthritis

Case details

A 63- year-old woman presents with a long history of joint pains. Physical examination reveals severely deformed fingers secondary to rheumatoid arthritis. The rheumatologist recommends Methotrexate. This drug inhibits which of the following conversions?

A. Dopamine to norepinephrine

B. Tyrosine to Dopa

C. Folate to dihydrofolate

D. Histidine to formiminoglutamate (FIGLU)

E. Norepinephrine to Vanillylmandelic acid

The correct answer is- C. Folate to dihydrofolate conversion.

The reaction is catalyzed by dihydrofolate reductase; the same enzyme catalyzes the conversion of Dihydrofolate to tetrahydrofolate. The enzyme is competitively inhibited by Methotrexate, which is also used as an anticancer drug. It is not known exactly how methotrexate works in rheumatoid arthritis, but it can reduce inflammation and slow the progression of the disease. Methotrexate is considered a disease-modifying antirheumatic drug (DMARD). DMARDs are also called immunosuppressive drugs or slow-acting antirheumatic drugs (SAARDs).

For details of Mechanism of action of methotrexate and side effects, follow the links-

http://www.namrata.co/methotrexate-mechanism-of-actionside-effects-and-significance/

http://usmle.biochemistryformedics.com/methotrexate-therapy-case-discussion/           

As regards other options

The conversion of Dopamine to norepinephrine is carried out by Dopamine β oxidase enzyme.

The conversion of Tyrosine to Dopa is carried out by Tyrosinase enzyme and

Histidine to formiminoglutamate (FIGLU) occurs during the metabolism of Histidine by first conversion to urocanic acid, then to 4-Imidazole 5-propionate and then to formiminoglutamate (FIGLU).

Norepinephrine to Vanillylmandelic acid occurs during degradation of norepinephrine.

Catecholamines are degraded in the liver by two enzymes, COMT (Catechol-O-Methyl-Transferase) and MAO (Mono amine Oxidase). By the action of COMT, epinephrine and Nor epinephrine are converted to metanephrine and nor metanephrine respectively. Both these products are further acted upon by MAO to form VMA (Vanillyl Mandelic acid) and MOPG (3-Methoxy 4- hydroxyphenylglycol). These products are further excreted in urine. The Excretory products are increased in Pheochromocytoma and that forms the basis for the diagnostic test.

 

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