Adenylosuccinate synthetase 2 (ADSS2)

Adenylosuccinate synthetase 2 (ADSS2) is a critical enzyme in the de novo purine biosynthetic pathway, specifically catalyzing the GTP-dependent conversion of inosine monophosphate (IMP) and L-aspartate into adenylosuccinate (UniProt: P30520). This reaction represents the first committed step in the synthesis of adenosine monophosphate (AMP) from IMP. Unlike the muscle-specific isoform ADSS1, ADSS2 is ubiquitously expressed and plays a vital role in maintaining cellular adenine nucleotide pools across various tissues (PubMed: 10430910). In the context of oncology, ADSS2 is often upregulated in rapidly proliferating cancer cells to meet the increased demand for nucleotides, making it a potential therapeutic target (PubMed: 28655770). Inhibitors such as hadacidin and the prodrug L-alanosine have been studied for their ability to deplete cellular AMP, leading to the inhibition of nucleic acid synthesis and cell death (PubChem: CID 5351125). However, the ubiquitous nature of ADSS2 presents challenges regarding systemic toxicity and the therapeutic window.

Other names

Adenylosuccinate synthetase, liver isozymeIMP--aspartate ligase 2AMPSase 2ADSSADE2Adenylosuccinate synthetase

Competitive inhibition of the enzyme, preventing the conversion of IMP to adenylosuccinate, thereby depleting AMP levels and inhibiting DNA/RNA synthesis (PubMed: 28655770; PubChem: CID 5351125).