Disease relevance of Adsl

• Identification of His141 in the active site of Bacillus subtilis adenylosuccinate lyase by affinity labeling with 6-(4-bromo-2,3-dioxobutyl)thioadenosine 5'-monophosphate [1].
• These novel analogs of adenylosuccinate were synthesized with this enzyme and their kinetic constants were determined with adenylosuccinate lyase purified from Ehrlich ascites cells [2].
• Thus, the ASL approach proved effective in identifying splicing events, which suggest that alternative splicing is important in melanoma development [3].

High impact information on Adsl

• Disruption of the purine nucleotide cycle by inhibition of adenylosuccinate lyase produces skeletal muscle dysfunction [4].
• Disruption of the purine nucleotide cycle during muscle stimulation was evidenced by a greater accumulation of adenylosuccinate, the substrate for adenylosuccinate lyase, in the animals receiving AICAriboside (0.60 +/- 0.10 vs. 0.05 +/- 0.01 nmol/mumol total creatine, P less than 0.0001) [4].
• When the compound 5-amino-4-imidazolecarboxamide riboside (AICAriboside) is phosphorylated to the riboside monophosphate in the myocyte it is an inhibitor of adenylosuccinate lyase, one of the enzymes of the purine nucleotide cycle [4].
• The present data demonstrate considerable alterations of the ODC/polyamine system in a reliable animal model of ASL, consistent with their role in neurodegeneration and in particular in motor neuron diseases [5].
• Two genes, Smstr3 and Adsl, not previously mapped in the mouse genome, were located on mouse Chromosome 15 [6].

Associations of Adsl with chemical compounds

• We conclude that 6-BDB-TAMP functions as a reactive adenylosuccinate analog in modifying His141 in the substrate-binding site of adenylosuccinate lyase, where it may serve as a general base accepting a proton from the succinyl group during catalysis [1].
• Adenylosuccinate lyase is also a participant in the purine nucleotide cycle which plays an important role in maintaining the AMP levels in muscle [7].
• In order to understand the structure/function and evolutionary relationships of the members of the fumarate gene family and to evaluate the possible existence of tissue specific isoforms of adenylosuccinate lyase, we have isolated and characterized the murine cDNA and gene encoding adenylosuccinate lyase [7].
• Adenylosuccinate lyase catalyzes two similar reactions in the de novo purine biosynthetic pathway; the cleavage of succinylaminoimidazole carboxamide ribotide to aminoimidazole carboxamide ribotide and fumarate and the cleavage of adenylosuccinate to adenylate and fumarate [7].
• Inhibition of adenylosuccinate lyase by L-alanosyl-5-aminoimidazole-4-carboxylic acid ribonucleotide (alanosyl-AICOR) [8].

References