Adenylosuccinate lyase (ADSL)

Adenylosuccinate lyase (ADSL) is an essential enzyme in purine metabolism, catalyzing two steps in the purine nucleotide biosynthetic pathway: the conversion of succinylaminoimidazole carboxamide ribotide (SAICAR) to aminoimidazole carboxamide ribotide (AICAR) and the conversion of adenylosuccinate (SAMP) to adenosine monophosphate (AMP) and fumarate. This enzyme is a homotetramer and part of the β-elimination superfamily, relying on an E1cb elimination reaction mechanism with unique catalytic residues such as His171 and Ser295 in humans. It plays a vital role in maintaining cellular nucleotide pools necessary for DNA/RNA synthesis, cellular energy metabolism, and cell division. Deficiency due to mutation in the ADSL gene leads to a rare autosomal recessive disorder characterized by severe neurological symptoms, developmental delay, and autism-like features due to accumulation of neurotoxic succinylpurines. While no approved drugs directly target ADSL in humans, its homologs in microbes have been investigated as potential antimicrobial drug targets via structure-based inhibitor design. Clinical management of deficiency focuses on supportive care and monitoring succinylpurine levels as biomarkers; experimental inhibitors and substrate analogs have been studied for structural and mechanistic insights.

Other names

AdenylosuccinaseASLAMPSASASEadenylosuccinate lyaseadenylosuccinase

Competitive inhibition of substrate binding (APBADP blocks conversion of adenylosuccinate to AMP/fumarate) and potential inhibition of microbial ADSL to block purine biosynthesis (antimicrobial strategy). No clinically approved drugs are known to interact directly with ADSL in humans.