Báo cáo khoa học: Argininosuccinate synthetase from the urea cycle to the citrulline–NO cycle

Argininosuccinate Synthetase: From the Urea Cycle to the Citrulline-NO Cycle

Authors: Annie Husson, Carole Brasse-Lagnel, Alain Fairand, Sylvie Renouf and Alain Lavoinne

Affiliation: ADEN, Institut Fédératif de Recherches Multidisciplinaires sur les Peptides no. 23 (IFRMP 23), Rouen, France

Field: Biochemistry / Molecular Biology

Document Content: This review article explores the multifaceted roles and regulation of argininosuccinate synthetase (ASS), an enzyme initially identified as crucial for urea synthesis in the liver. Recent discoveries have highlighted its significance in the citrulline-NO cycle, potentially acting as a rate-limiting step in nitric oxide (NO) production. The article contrasts the distinct regulatory mechanisms of ASS in the liver, where it’s influenced by hormones and nutrients, versus NO-producing cells, where pro-inflammatory signals are dominant. It delves into the transcriptional regulation of ASS, noting that while factors are identified, the precise molecular mechanisms remain largely unelucidated. The review also touches upon the enzyme’s conserved nature across species and its potential as a target for gene therapy in conditions like citrullinemia.

Detailed Table of Contents:

• Argininosuccinate synthetase (ASS, EC 6.3.4.5)
• The citrulline-NO cycle
• Regulation of ASS gene expression
• Hepatic vs. NO-producing cells
• Transcriptional regulation
• Molecular mechanisms
• ASS protein: a ubiquitous enzyme
• ASS, a highly conserved enzyme
• ASS, a targeted protein
• Cell/tissue specific regulation
• ASS, a key step in urea production
• ASS, a key step in arginine production
• ASS, a potential limiting step in NO production
• ASS, a known but poorly understood gene
• ASS, an unusual promoter
• ASS, a model for gene therapy
• Concluding remarks