Deoxynucleotides

The enzyme DNA polymerase, which uses deoxynucleoside triphosphates as substrates, makes DNA. To ensure enough precursors for DNA synthesis, two reactions must occur. First, the 2′ position of the ribose ring of ribonucleotides must be reduced from a C‐OH to a C‐H before the nucleotides can be used for DNA synthesis. Secondly, the thymine ring must be made by addition of a methyl group to uridine.

The small protein thioredoxin supplies reducing equivalents to ribonucleotide reductase for the ribose ring reduction. Thioredoxin is itself reduced by another protein, thioredoxin reductase, a flavoprotein. Reduced glutathione can also carry reducing equivalents to ribonucleotide reductase. In both cases, the ultimate source of reducing equivalents is NADPH.

The regulation of ribonucleotide reductase is complex, with many feedback reactions used to keep the supplies of deoxynucleotides in balance. For example, dGTP and dTTP are feedback inhibitors of their own formation. Each is also an activator of the synthesis of the complementary nucleotide (dCDP or dADP), while dATP is an inhibitor of the reductions to make dADP, dCDP, dGDP, and dUDP. These control functions keep the supply of deoxynucleotides in balance, so that a roughly equivalent amount of each remains available for DNA synthesis.