page_title: Argininosuccinate synthase
section_title: Mechanism
hierarchical_section_title: Argininosuccinate synthase / Mechanism
caption_attribution_description: English: Formation of L-argininosuccinate from L-citrulline, ATP, and L-aspartate, catalyzed by argininosuccinate synthetase.
context_page_description: Argininosuccinate synthase or synthetase is an enzyme that catalyzes the synthesis of argininosuccinate from citrulline and aspartate. In humans, argininosuccinate synthase is encoded by the ASS gene located on chromosome 9.
  ASS is responsible for the third step of the urea cycle and one of the reactions of the citrulline-NO cycle.
context_section_description: In the first step of the catalyzed reaction, citrulline attacks the α-phosphate of ATP to form citrulline adenylate, a reactive intermediate. The attachment of AMP to the ureido (urea-like) group on citrulline activates the carbonyl center for subsequent nucleophilic attack. This activation facilitates the second step, in which the α-amino group of aspartate attacks the ureido group. Attack by aspartate is the rate-limiting step of the reaction. This step produces free AMP and L-argininosuccinate.
  Thermodynamically, adenylation of the citrulline ureido group is more favorable than the analogous phosphorylation. Additionally, attack by citrulline at the α-phosphate of ATP produces an equivalent of pyrophosphate, which can be hydrolyzed in a thermodynamically favorable reaction to provide additional energy to drive the adenylation.
caption: Reaction catalyzed by argininosuccinate synthetase. Adapted from Goto et al. 2003.[5]
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