AcylAMPs

AcylAMPs, or acyl-adenylates, are reactive intermediates formed during the activation of carboxylic acids by ATP-dependent enzymes. They consist of an acyl group linked to adenosine monophosphate (AMP) through a mixed anhydride bond. Acyl-AMPs are typically short-lived and are generated at the first step of a two-step catalytic cycle in acyl-CoA synthetases and related adenylation enzymes.

In the canonical mechanism, an enzyme couples the carboxylate substrate to ATP to form the acyl-AMP intermediate with the release of pyrophosphate. In a second step, the acyl moiety is transferred to another nucleophile, most commonly coenzyme A to form acyl-CoA, or to a carrier protein or other nucleophile in specialized biosynthetic pathways. The acyl-AMP stage thus serves as a activated carrier that enables subsequent acyl- group transfer under physiological conditions.

Biological roles of acyl-AMP intermediates are widespread. They are central to fatty acid activation for lipid metabolism and energy production, and they also operate in various secondary metabolic pathways, including polyketide and nonribosomal peptide biosynthesis, where acyl-adenylate chemistry facilitates substrate loading and chain assembly. The transient nature and reactivity of acyl-AMPs pose challenges for detection, but they can be inferred from kinetic studies, trapping experiments, and the detection of downstream products such as acyl-CoA or acylated carrier proteins.

See also acyl-CoA synthetases, adenylation domains, acyl carrier proteins.