Carbamoyl phosphate synthesis

In the first step of the carbamoyl phosphate synthesis pathway, bicarbonate is phosphorylated by ATP to form carboxyphosphate and ADP. Ammonia then reacts with carboxyphosphate to form carbamic acid and inorganic... 

E) Glutamine is the substrate that directly provides the nitrogen for carbamoyl phosphate synthesis... 

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... 

The metabolic interrelationship between mitochondrial carbamoyl phosphate synthesis to urea formation and to cytosolic carbamoyl phosphate channeled into pyrimidine biosynthesis. In ornithine transcarbamoyiase (OTC) deficiency, mitochondrial carbamoyl phosphate diffuses into the cytosol and stimulates pyrimidine biosynthesis, leading to orotidinuria. Administration of allopurinol augments orotidinuria by increasing the flux in the pyrimidine biosynthetic pathway. CPS = Carbamoyl phosphate synthase, AT = aspartate transcarbamoyiase, D = dihydroorotase, DH = dihydroorotate dehydrogenase, OPRT = orotate phosphoribosyltransferase, XO = xanthine oxida.se,... 

The synthesis of urea in the liver is the major route for the removal of NH4. A blockage of carbamoyl phosphate synthesis or of any of the four steps of the urea cycle has devastating consequences because there is no alternative pathway for the synthesis of urea. All defects in the urea... 

A defect in carbamoyl phosphate synthesis would cause increased NH/ concentrations, as would a defect in any of the four reactions that condense carbamoyl phosphate with ornithine and regenerate the ornithine. Essentially, blocking a biochemical pathway at any of its steps may lead to increased concentrations of any of the precursors or members of the pathway. 

Carbamoyl phosphate synthesis from ammonia represents one of the prominent activities in ureotelic livers [78]. The enzyme requires N-acetylglutamate and is distinct from the enzyme responsible for carbamoyl phosphate synthesis in extrahepatic tissues and in the livers of uricotelic animals. This second enzyme utilizes glutamine [79], rather than ammonia as the primary nitrogen donor and is found in mushrooms, Escherichia coli, yeast, Ehrlich ascites tumour and several other animal tissues [80]. This enzyme is carbamoyl phosphate synthetase II (ATP carbamate phosphotransferase, EC 2.7.2.2) and catalyses the following reaction ... 

Figure 2. Domain Structure of CAD. Each domain, submdomain and the two major linkers (Ink) are represented by segments approximately proportional to their size. Carbamoyl phosphate synthesis involves the concerted action of the GLN domain and the two CPS subdomains, CPS.A and CPS.B. The second and third steps of the pathway are catalyzed by the DHO and ATC domains.

Figure 3. Partial Reactions in Carbamoyl Phosphate Synthesis...

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