Arginine biosynthesis (WP275)

Saccharomyces cerevisiae

The first five steps of arginine biosynthesis in S. cerevisiae take place in the mitochondrion (CITS: [11553611])(CITS: [Hinnebusch]). This part of the pathway is known as the acetylated derivatives cycle because the acetyl group that is added to L-glutamate in the first step of the pathway is recycled via N-acetylglutamate generated in the fifth step. The enzymes that catalyze the second and third steps are encoded by a single gene (ARG5,6) that is translated into a pre-protein which is imported into mitochondria and cleaved there to yield two enzymes, N-acetylglutamate kinase and N-acetylglutamyl-phosphate reductase (CITS: [1649049]). These enzymes form a complex with each other and with N-acetylglutamate synthase, the first enzyme in the pathway, which may have implications for regulation of their activity (CITS: [11553611]). The mitochondrial steps of the arginine biosynthesis pathway result in the formation of ornithine, which is exported to the cytoplasm by the transporter Ort1p (CITS: [8798783]). In the cytoplasm, L-ornithine is converted to L-arginine in three reactions mediated by ornithine carbamoyltransferase, arginosuccinate synthase, and argininosuccinate lyase. Transcription of genes of the arginine biosynthetic pathway, as well as of other amino acid biosynthetic pathways, is activated by the transcription factor Gcn4p under conditions of amino acid starvation (CITS: [11390663])(CITS: [Hinnebusch]). Transcription of ARG1, ARG3, ARG5,6, and ARG8 is also repressed in the presence of arginine by the ArgR/Mcm1p complex, which consists of Arg80p, Arg81p, Arg82p, and Mcm1p (CITS: [14563547]). The transcriptional activator Gcn4p interacts with subunits of the ArgR/Mcm1p repressor, allowing for fine-tuning of transcriptional control in response to arginine availability (CITS: [15289616]). SOURCE: SGD pathways,


Meredith Braymer , Martina Summer-Kutmon , Christine Chichester , Egon Willighagen , Eric Weitz , and Kristina Hanspers


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Saccharomyces cerevisiae



Pathway Ontology

arginine biosynthetic pathway


Label Type Compact URI Comment
N-acetyl-L-glutamate Metabolite chebi:44337
N-acetyl-L-glutamate Metabolite chebi:44337
2-oxoglutarate Metabolite chebi:16810
fumarate Metabolite chebi:29806
Coenzyme A Metabolite cas:64885-97-8
ADP Metabolite cas:58-64-0
acetyl-CoA Metabolite cas:72-89-9
ATP Metabolite cas:1927-31-7
L-glutamate Metabolite cas:56-86-0
L-arginine Metabolite cas:74-79-3
L-ornithine Metabolite cas:70-26-8
citrulline Metabolite cas:372-75-8
NADPH Metabolite cas:53-57-6
pyrophosphate Metabolite cas:2466-09-3
ATP Metabolite cas:1927-31-7
L-glutamate Metabolite cas:56-86-0
phosphate Metabolite cas:14265-44-2
L-glutamate Metabolite cas:56-86-0
phosphate Metabolite cas:14265-44-2
ARG4 GeneProduct sgd:S000001060
ARG2 GeneProduct sgd:S000003607
ARG5,6 GeneProduct sgd:S000000871
ARG8 GeneProduct sgd:S000005500
ARG1 GeneProduct sgd:S000005419
ARG5,6 GeneProduct sgd:S000000871
ARG3 GeneProduct sgd:S000003624
ECM40 GeneProduct sgd:S000004666


  1. A new yeast metabolon involving at least the two first enzymes of arginine biosynthesis: acetylglutamate synthase activity requires complex formation with acetylglutamate kinase. Abadjieva A, Pauwels K, Hilven P, Crabeel M. J Biol Chem. 2001 Nov 16;276(46):42869–80. PubMed Europe PMC Scholia
  2. The N-acetylglutamate synthase/N-acetylglutamate kinase metabolon of Saccharomyces cerevisiae allows co-ordinated feedback regulation of the first two steps in arginine biosynthesis. Pauwels K, Abadjieva A, Hilven P, Stankiewicz A, Crabeel M. Eur J Biochem. 2003 Mar;270(5):1014–24. PubMed Europe PMC Scholia