Adenylosuccinate synthetase isozyme 1 (ADSSL1) (ADSSL1)

Adenylosuccinate synthetase isozyme 1 (ADSSL1) is a muscle-specific enzyme that plays a critical role in the purine nucleotide cycle (PNC) by catalyzing the conversion of inosine monophosphate (IMP) to adenylosuccinate, the first step in de novo AMP biosynthesis [4, 8]. This process is essential for maintaining the adenine nucleotide pool and supporting energy metabolism in high-demand tissues like skeletal and cardiac muscle [1, 8]. Mutations in the ADSSL1 gene cause ADSSL1 myopathy, an ultra-rare autosomal recessive neuromuscular disorder characterized by progressive distal muscle weakness, facial weakness, and in some cases, cardiac and respiratory failure [1, 11]. Currently, there are no approved pharmacological treatments for this condition [13]. However, therapeutic strategies under investigation include gene replacement therapy to restore enzyme function, small-molecule stimulants to enhance residual enzyme activity, and the administration of downstream metabolites like adenylosuccinic acid or inosine to bypass the metabolic block and improve muscle energetics [13, 15, 17]. Research also suggests that ADSSL1 may promote cardiomyocyte proliferation and cardiac regeneration, making it a potential target for treating myocardial infarction [17].

Other names

Adenylosuccinate synthase 1Adenylosuccinate synthetase-like 1AMPSase 1AdSS 1IMP--aspartate ligase 1M-type adenylosuccinate synthetaseAdenylosuccinate synthetase, muscle isozymeAdenylosuccinate synthetase, basic isozyme

Gene replacement therapy, enzyme stimulation, and metabolite supplementation to restore purine homeostasis and muscle energetics.