3phosphoadenosinecontaining

3-Phosphoadenosine-containing compounds refer to molecules that include a phosphate group attached to the 3' position of the ribose in adenosine within a nucleotide framework. This structural motif appears in several biologically important activated intermediates, particularly those involved in sulfate metabolism and nucleotide turnover.

The most notable example is 3'-phosphoadenosine-5'-phosphosulfate (PAPS). PAPS serves as the universal activated sulfate donor for sulfotransferase enzymes, which attach sulfate groups to a wide range of substrates, including hormones, neurotransmitters, drugs, and extracellular macromolecules. In the course of sulfation, PAPS is converted to 3'-phosphoadenosine-5'-phosphate (PAP), which can act as a byproduct and, in some contexts, as a signaling molecule. PAP is typically dephosphorylated by PAP phosphatases to re-enter nucleotide metabolism.

Biosynthesis of PAPS begins with inorganic sulfate activating to adenosine 5'-phosphosulfate (APS) by ATP sulfurylase. APS is then phosphorylated to PAPS by APS kinase. In many organisms, the two activities reside on a bifunctional enzyme. The PAPS produced is then used by sulfotransferases, while PAP accumulates as a consequence of the transfer reaction and is subsequently metabolized.

Biological and clinical relevance centers on the sulfation pathway’s role in detoxification, hormone regulation, and drug metabolism. Variations in PAPS availability or sulfotransferase activity can influence the efficacy and fate of xenobiotics and endogenous molecules. Analytical and biochemical studies of 3-phosphoadenosine-containing compounds inform understanding of sulfate biology and related disorders.

See also: adenosine nucleotides; sulfation; PAPS; PAP.