Synthetases

Synthetases are enzymes that catalyze the formation of chemical bonds by condensing substrates, often using energy from ATP hydrolysis to drive the reaction. They typically activate a substrate and then transfer it to a recipient molecule, producing a new product with the release of inorganic phosphate or pyrophosphate. The term is used for a broad class of enzymes that generate activated intermediates, such as acyl- or aminoacyl-derivatives, enabling subsequent biosynthetic steps.

Aminoacyl-tRNA synthetases are among the most studied synthetases. They attach the appropriate amino acid to its corresponding transfer RNA, a central step in translating the genetic code. There are about 20 distinct aaRS enzymes, one for each standard amino acid. They activate the amino acid by forming an aminoacyl-AMP intermediate and then transfer the aminoacyl group to the 3' end of tRNA. Many aaRS possess editing domains that correct misactivated amino acids, contributing to translational accuracy. They are grouped into two structural classes, I and II, based on active-site architecture and sequence motifs.

Other synthetases participate in metabolism beyond translation. Examples include glutamine synthetase, which forms glutamine from glutamate and ammonia using ATP; carbamoyl phosphate synthetase, which generates carbamoyl phosphate from bicarbonate or CO2, ammonia, and ATP; and acetyl-CoA synthetase, which activates acetate to acetyl-CoA. These enzymes commonly generate activated intermediates that enable downstream biosynthetic transformations.

Mechanistically, many synthetases operate via a two-step process: activation of a substrate by ATP to form an activated intermediate, followed by transfer to a nucleophile on a second substrate. Synthetases are essential for metabolism, protein synthesis, and various biotechnological applications.