Enzymatic Reduction of Ribonucleotides: Biosynthesis Pathway of Deoxyribonucleotides

Ribonucleotide reductases are enzymes that synthesize the deoxyribonucleotides required for the replication of DNA in dividing cells. They thus have a key function for the growth of microorganisms and of all plant and animal tissues. The enzymes reduce all four purine and pyrimidine ribonucleotides (as the 5′‐diphosphates or triphosphates) with direct substitution of the 2′‐hydroxyl group by hydrogen. The physiological reducing agents are the mercapto groups of thioredoxins, a group of small proteins, which are regenerated from the oxidized form by NADPH‐dependent thioredoxin reductases. There are two known types of ribonucleotide reductases (I and II), which catalyze hydrogen transfer with the aid of protein‐bound iron ions or of 5′‐deoxyadenosylcobalamin (coenzyme B 12 ); free radicals can be detected in both cases. The enzymes are regulated by effector nucleotides. There may exist a homeostatic mechanism, which guarantees the supply of DNA precursors to the cell.