N-acetylglutamate synthase

In view of the toxicity of ammonia, complete absence of any one of the enzymes of the cycle is fatal. Nonetheless, disorders of the cycle do occur, which are caused by a low activity of one of the enzymes or carbamoyl phosphate synthetase. In addition, defects in N-acetylglutamate synthase have been reported, but they are very rare. With the exception of ornithine transcarbamoylase, the deficiencies have an autosomal recessive mode of inheritance. The transcarbamoylase deficiency is inherited as an X-linked dominant trait, usually lethal in male patients. A deficiency of carbamoyl phosphate synthetase, ornithine transcarbamoylase or argininosuccinate synthetase results in accumulation and excretion of citrulline. A deficiency of argininosuccinate lyase results in the accumulation and excretion of argininosuccinate and arginine (Table 10.5). The abbreviations CPSD, OTCD, ASD, ALD and AD stand, respectively, for the deficiencies of these enzymes, where D stands for deficiency. 

ACETYL-CoA ACYLTRANSFERASE ACETYL-CoAACP TRANSACYLASE ACETYL-CoA CARBOXYLASE ACETYL-CoA SYNTHETASE N-ACETYLGLUTAMATE SYNTHASE... 

Caldovic L, Morizono H, Daikhin Y, Nissim I, McCarter RJ, Yudkoff M, Tuchman M. Restoration of ure-agenesis in N-acetylglutamate synthase deficiency by N-carbamylglutamate. J Pediatr 2004 145(4) 552-4. 

N-Acetylglutamate synthase deficiency p Glut, Cit, Argt, Lysj... 

Table 2.1.9 Changes of blood amino acids in various primary inherited defects and as a result of secondary changes. ASA Argininosuccinic acid, CPS carbamoyl phosphate synthase, LPI Lysinuric protein intolerance, MAD multiple acyl-CoA dehydrogenation, MSUD maple syrup urine disease, NAGS N-acetylglutamate synthase, NKH nonketotic hyperglycinemia, NTBC 2-(2-nitro-4-3 trifluoro-methylbenzoyl)-1,3-cyclohexanedione, OCT Ornithine carbamoyltransferase,...

Pauwels, K. Abadjieva, A. Hilven, P. Stankiewicz, A. Crabeel, M. The N-acetylglutamate synthase/N-acetylglutamate kinase metabolon of Saccharo-myces cerevisiae allows co-ordinated feedback regulation of the first two steps in arginine biosynthesis. Eur. J. Biochem., 270, 1014-1024 (2003)... 

Integrates the latest on regulation of reactions throughout the chapter, with new material on genetic defects in urea cycle enzymes, and updated information on the regulatory function of N-acetylglutamate synthase. 

Formation of urea in hepatocytes. NAGS = N-acetylglutamate synthase CPSI = carbamoylphosphate synthase I OCT = ornithine carbamoyltransferase C-OT = citrulline-omithine translocase AS = argininosuccinate synthase AL = argininosuccinate lyase A = arginase. — -> indicates the absolute requirement of N-acetylglutamate for CPSI activity. 

Carbamoyl phosphate synthesis requires amino acid acetyltransferase (N-acetylglutamate synthase, mitochondrial) and carbamoyl-phosphate synthase I (CPSI). N-Acetylglutamate (NAG) is an obligatory positive effector of CPSI. NAG synthase is under positive allosteric modulation by arginine and product inhibition by NAG. Depletion of CoA-SH decreases NAG synthesis and ureage-nesis. This situation can occur in organic acidemias (e.g., propionic acidemia Chapter 18), in which organic acids produced in excess compete for CoA-SH for formation... 

N-Acetylglutamate is synthesized from acetyl GoA and glutamate. Once again, acetyl CoA serves as an activated acetyl donor. This reaction is catalyzed by N-acetylglutamate synthase. 

The urea cycle enzymes are controlled in the short term by the concentrations of their substrates. Carbamoyl phosphate synthetase I is also allosterically activated by N-acetylglutamate. This latter molecule is a sensitive indicator of the cell s glutamate concentration. (Recall that a significant amount of NH4 is derived from glutamate.) N-acetylglutamate is produced from glutamate and acetyl-CoA in a reaction catalyzed by N-acetylglutamate synthase. 

Propionyl CoA and methylmalonyl CoA both inhibit N-acetylglutamate synthase activity in slices of liver tissue. What clinical symptom would you expect to see in patients suffering from methylmalonic aciduria as a result of this inhibition ... 

A novel type of N-acetylglutamate synthase is involved in the first step of arginine biosynthesis in Corynebacterium glutamicum. BMC Genomics,... 

Haberle J. Role of caiglumic add in the treatment of acute hyperammonemia due to N-acetylglutamate synthase defidency. Ther Qin Risk Manag. 2011 7 327-32. 

Reduced nicotinamide adenine dinucleotide a-AT-acetylgalactosaminidase N-acetylglutamate synthase Neonatal adrenal leukodystrophy... 

N-Acetylglutamate is itself synthesized in the mitochondria by the reaction of glutamate with acetyl-CoA that is catalysed by N-acetylglutamate synthase (acetyl-CoA glutamate... 

Yamada, E. and Y. Wakabayashi, 1991. Development of pyrroline-5-carboxylate synthase and N-acetylglutamate synthase and their changes in lactation and aging. Arch. Biochem. Biophys. 291, 15-23. 

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