Case discussion- Treatment with Hydroxyurea- A case of chronic myelogenous Leukemia

Case Details

A physician evaluates a 32-year-old patient for fatigue. The patient is found to have an elevated white blood cell count and an enlarged spleen. A referral to an oncologist results in a diagnosis of chronic myelogenous leukemia. Treatment with hydroxyurea, a ribonucleotide reductase inhibitor is begun. The normal functioning of this enzyme is to do which of the followings?

A. Converts xanthine to uric acid

B. Converts ribonucleotides to deoxy ribonucleotides

C. Degrades guanine to xanthine

D. Degrades AMP to IMP

E. Converts PRPP to phosphoribosylamine

Answer- The correct answer is- B

Hydroxyurea is prescribed to the patients suffering from myeloproliferative disorders, chronic myelogenous leukemia, AIDS, psoriasis and sickle cell anemia. In the treatment of sickle-cell disease, hydroxyurea increases the concentration of fetal hemoglobin.  Hydroxyurea is a drug known to act by inhibiting Ribonucleotide reductase.

Ribonucleotide Reductase converts ribonucleotides to deoxyribonucleotides.

Reduction of the 2′-hydroxyl of purine and pyrimidine ribonucleotides, catalyzed by the ribonucleotide reductase complex (Figure), forms deoxyribonucleoside diphosphates (dNDPs). The enzyme complex is active only when cells are actively synthesizing DNA. Reduction requires thioredoxin, thioredoxin reductase, and NADPH. The immediate reductant, reduced thioredoxin, is produced by NADPH: thioredoxin reductase (Figure). Reduction of ribonucleoside diphosphates (NDPs) to deoxyribonucleoside diphosphates (dNDPs) is subject to complex regulatory controls that achieve balanced production of deoxyribonucleotides for synthesis of DNA.

Ribonucleotide reductase  Ribonucleotide reductase    

Figure- Conversion of Ribonucleoside diphosphate to 2’deoxy ribonucleoside diphosphate

Inhibition of this enzyme leads to impaired formation of deoxy ribonucleotides, DNA replication is affected and because of that the rapidly proliferating cells are also affected.

The conversion of xanthine to uric acid is carried out by Xanthine oxidase enzyme.

Similarly the conversion of guanine to xanthine is also carried out by xanthine oxidase.

AMP to IMP conversion is carried out by AMP deaminase enzyme and the conversion of PRPP to ribosylamine is carried out by Amido transferase.

Hence the right answer is conversion of Ribonucleotide to deoxyribonucleotides

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