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Literature summary extracted from

  • Nakagawa, T.; Lomb, D.J.; Haigis, M.C.; Guarente, L.
    SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle (2009), Cell, 137, 560-570.
    View publication on PubMedView publication on EuropePMC

Activating Compound

EC Number Activating Compound Comment Organism Structure
6.3.4.16 N-acetyl-L-glutamate i.e. NAG, dependent on the essential cofactor Mus musculus
6.3.4.16 SIRT5 a sirtuin enzyme, that deacetylates CPSI, which activates CPSI. During fasting, NAD in liver mitochondria increases, thereby triggering SIRT5 deacetylation of CPS1 and adaptation to the increase in amino acid catabolism. SIRT5 KO mice fail to up-regulate CPS1 activity and show elevated blood ammonia during fasting, overview Mus musculus

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.3.1.B43 mitochondrial matrix
-
 Mus musculus 5759
-
6.3.4.16 mitochondrion
-
 Mus musculus 5739
-

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.3.1.B43 NAD+ + [carbamoyl phosphate synthetase 1]-N6-acetyl-L-lysine Mus musculus SIRT5 plays a pivotal role in ammonia detoxification and disposal by activating carbamoyl phosphate synthetase 1 (CPS1) an enzyme, catalyzing the initial step of the urea cycle for ammonia detoxification and disposal. SIRT5 deacetylates CPS1 and up-regulates its activity. During fasting, NAD+ in liver mitochondria increases, thereby triggering SIRT5 deacetylation of CPS1 and adaptation to the increase in amino acid catabolism. Indeed, SIRT5 KO mice fail to up-regulate CPS1 activity and show elevated blood ammonia during fasting nicotinamide + [carbamoyl phosphate synthetase 1]-L-lysine + 2'-O-acetyl-ADP ribose
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.3.1.B43 Mus musculus Q8K2C6
-
-
6.3.4.16 Mus musculus
-
-
-

Posttranslational Modification

EC Number Posttranslational Modification Comment Organism
6.3.4.16 additional information deacetylation by SIRT5 activates CPSI Mus musculus

Source Tissue

EC Number Source Tissue Comment Organism Textmining
6.3.4.16 liver
-
 Mus musculus
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.1.B43 NAD+ + [carbamoyl phosphate synthetase 1]-N6-acetyl-L-lysine
-
 Mus musculus nicotinamide + [carbamoyl phosphate synthetase 1]-L-lysine + 2'-O-acetyl-ADP ribose
-
 ?
2.3.1.B43 NAD+ + [carbamoyl phosphate synthetase 1]-N6-acetyl-L-lysine SIRT5 plays a pivotal role in ammonia detoxification and disposal by activating carbamoyl phosphate synthetase 1 (CPS1) an enzyme, catalyzing the initial step of the urea cycle for ammonia detoxification and disposal. SIRT5 deacetylates CPS1 and up-regulates its activity. During fasting, NAD+ in liver mitochondria increases, thereby triggering SIRT5 deacetylation of CPS1 and adaptation to the increase in amino acid catabolism. Indeed, SIRT5 KO mice fail to up-regulate CPS1 activity and show elevated blood ammonia during fasting Mus musculus nicotinamide + [carbamoyl phosphate synthetase 1]-L-lysine + 2'-O-acetyl-ADP ribose
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.3.1.B43 SIRT5
-
 Mus musculus
6.3.4.16 carbamoyl phosphate synthetase 1
-
 Mus musculus
6.3.4.16 CPS1
-
 Mus musculus

Expression

EC Number Organism Comment Expression
6.3.4.16 Mus musculus nutrient depletion does not increase CPS1 protein levels in wild-type or KO cells additional information

General Information

EC Number General Information Comment Organism
2.3.1.B43 metabolism SIRT5 plays a pivotal role in ammonia detoxification and disposal by activating carbamoyl phosphate synthetase 1 an enzyme, catalyzing the initial step of the urea cycle for ammonia detoxification and disposal Mus musculus
6.3.4.16 metabolism CPS1 catalyzes the initial step of the urea cycle for ammonia detoxification and disposal Mus musculus