The second major route of enzymatic fragmentation of ATP and congeners such as GTP, CTP, and UTP involves directed attack of cosubstrate nucleophiles at P_alpha of ATP or NTPs. This transfers the AMP moiety in the case of ATP (adenylyl transfer) and more generally the NMP moiety from the other three nucleoside triphosphates (nucleotidyl transfers) to a nucleophilic atom of a cosubstrate. This is the preferred mode of cleavage of the ATP or NTP side chain in the assembly of linear condensed biological macromolecules—nucleic acids, proteins, and polysaccharides. Thermodynamically favored ATP or NTP hydrolysis drives otherwise unfavorable equilibria, especially against the entropy barriers, in each chain elongation step in biopolymer growth. In both RNA and DNA biosynthesis (using 2′deoxyNTPs) the NMP or 2′dNMP moiety is stably incorporated in each chain extension step by RNA or DNA polymerases. The resultant internucleotide phosphodiester bond is the sole covalent linkage in RNA and DNA macromolecules. The intermediate aminoacyl-AMPs in each step of protein biosynthesis are kinetically unstable and are captured as aminoacyl-tRNAs to be ferried to ribosomes by protein chaperones. In polysaccharide assembly the activated monomers arising from nucleotidyl transfer enzyme action are corresponding nucleoside diphosphosugars.