Lippincott® Illustrated Reviews: Biochemistry, 8e by unknow

Author:unknow
Language: eng
Format: epub

Figure 22.12

Conversion of ribonucleotides to deoxyribonucleotides. NADP(H) = nicotinamide adenine dinucleotide phosphate; dATP = deoxyadenosine triphosphate.

Deoxyribonucleotide synthesis regulation

Ribonucleotide reductase is responsible for maintaining a balanced supply of the deoxyribonucleotides required for DNA synthesis. Consequently, the regulation of the enzyme is complex. In addition to the catalytic site, R1 contains two distinct allosteric sites involved in regulating enzymic activity (Fig. 22.13).

Clinical Application 22.1: Hydroxyurea

The drug hydroxyurea (hydroxycarbamide) inhibits ribonucleotide reductase, thereby inhibiting the generation of substrates for DNA synthesis. The drug is an antineoplastic agent and is used in the treatment of cancers such as melanoma. Hydroxyurea is also used in the treatment of sickle cell anemia (see p. 38). However, the increase in fetal hemoglobin seen with hydroxyurea is because of changes in gene expression and not to ribonucleotide reductase inhibition.

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