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Argininosuccinate synthetase (ASS, EC 6.3.4.5) catalyses the condensation of citrulline and aspartate to form argini-nosuccinate, the immediate precursor of arginine. First identified in the liver as the limiting enzyme of the urea cycle, ASS is now recognized as a ubiquitous enzyme in mamma-lian tissues. Indeed, discovery of the citrulline–NO cycle has increased interest in this enzyme that was found to represent a potentiallimiting step in NO synthesis. | Eur. J. Biochem. 270 1887-1899 2003 FEBS 2003 doi 10.1046 j.1432-1033.2003.03559.x REVIEW ARTICLE Argininosuccinate synthetase from the urea cycle to the citrulline NO cycle Annie Husson Carole Brasse-Lagnel Alain Fairand Sylvie Renouf and Alain Lavoinne ADEN Institut Federatif de Recherches Multidisciplinaires sur les Peptides no. 23 IFRMP 23 Rouen France Argininosuccinate synthetase ASS EC 6.3.4.5 catalyses the condensation of citrulline and aspartate to form argini-nosuccinate the immediate precursor of arginine. First identified in the liver as the limiting enzyme of the urea cycle ASS is now recognized as a ubiquitous enzyme in mammalian tissues. Indeed discovery of the citrulline-NO cycle has increased interest in this enzyme that was found to represent a potential limiting step in NO synthesis. Depending on arginine utilization location and regulation of ASS are quite different. In the liver where arginine is hydrolyzed to form urea and ornithine the ASS gene is highly expressed and hormones and nutrients constitute the major regulating factors a glucocorticoids glucagon and insulin particularly control the expression of this gene both during development and adult life b dietary protein intake stimulates ASS gene expression with a particular efficiency of specific amino acids like glutamine. In contrast in NO-producing cells where arginine is the direct substrate in the NO synthesis ASS gene is expressed at a low level and in this way proinflammatory signals constitute the main factors of regulation of the gene expression. In most cases regulation of ASS gene expression is exerted at a transcriptional level but molecular mechanisms are still poorly understood. Keywords argininosuccinate synthetase urea cycle arginine citrulline-NO cycle transcription regulation .NA binding sequences. Argininosuccinate synthetase ASS L-citrulline L-aspartate ligase EC 6.3.4.5 was first identified 50 years ago in the liver 1 but was more recently recognized as a ubiquitous .
