Ornithine reactions, with carbamoyl phosphate

This enzyme [EC 2.1.3.3], also known as ornithine car-bamoyltransferase and citrulline phosphorylase, catalyzes the reaction of carbamoyl phosphate with L-orni-thine to produce L-citrulline and orthophosphate. 

STEPS 1-2 OF FIGURE 20.5 ARCININOSUCCINATE SYNTHESIS The urea cycle begins with a nucleophilic acyl substitution reaction of the nonprotein amino acid ornithine with carbamoyl phosphate to produce citrulline. The side-chain -NH2 group of ornithine is the nucleophile, phosphate ion is the... 

The carbamoyl phosphate, which functions as an activated carbamoyl group donor, now enters the urea cycle. The cycle has four enzymatic steps. First, carbamoyl phosphate donates its carbamoyl group to ornithine to form citrulline, with the release of Pj (Fig. 18-10, step ). Ornithine plays a role resembling that of oxaloacetate in the citric acid cycle, accepting material at each turn of the cycle. The reaction is catalyzed by ornithine transcarbamoylase, and the citrulline passes from the mitochondrion to the cytosol. 

Formation of citrulline Ornithine and citrulline are basic amino acids that participate in the urea cycle. [Note They are not incorporated into cellular proteins, because there are no codons for these amino acids (see p. 429).] Ornithine is regenerated with each turn of the urea cycle, much in the same way that oxaloacetate is regenerated by the reactions of the citric acid cycle (see p 109). The release of the high-energy phosphateof carbamoyl phosphate as inorganic phosphate drives the reaction in the forward direction. The reaction product, citrulline, is trans ported to the cytosol. 

In the urea cycle ammonia is first combined with C02 to form carbamoyl phosphate. This then combines with ornithine to form citrulline. Citrulline then condenses with aspartate, the source of the second nitrogen atom in urea, to form argininosuccinate. This compound is in turn split to arginine and fumarate, and the arginine then splits to form urea and regenerate ornithine The first two reactions take place in the mitochondria of liver cells, the remaining three in the cytosol. 

Ammonia is condensed with bicarbonate and ATP in the mitochondrion to form carbamoyl phosphate in a reaction catalyzed by carbamoyl phosphate synthetase I. Two molecules of ATP are used in this reaction one provides the phosphate, and the other is hydrolyzed to ADP and inorganic phosphate (P) to provide the energy that drives the reaction to products. The activated carbamoyl group is then transferred to the amino acid ornithine by the mitochondrial enzyme ornithine transcarbamoylase to form citrulline. Citrulline then is transported out of the mitochondrion to the cytosol, where the rest of the reactions... 

Step 2. The carbamoyl phosphate thus produced condenses with the amino acid ornithine to produce the amino acid citrulline. This reaction also occurs in the mitochondria and is catalyzed by the enzyme ornithine transcarbamoylase. 

Carbamoyl phosphate reacts with ornithine to form citrulline (see Fig. 38.12). The high- energy phosphate bond of carbamoyl phosphate provides the energy required for this reaction, which occurs in mitochondria and is catalyzed by ornithine transcarbamoylase. The product citrulline is transported across the mitochondrial membranes in exchange for cytoplasmic ornithine and enters the cytosol. The carrier for this transport reaction catalyzes an electroneutral exchange of the two compounds. 

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 (CP) serves as a substrate for two separate transcarbamylase enzymes. One of these, in a reaction with aspartic acid, yields carbamoyl aspartate, the first specific precursor in the UMP pathway the other, in a similar reaction with ornithine, has a similar role for the eventual synthesis of arginine. Thus, CP serves as a common precursor for both UMP and arginine, and special regulation of its formation must be obtained to assure a balanced supply of both end products. The problem is handled in a variety of ways by different organisms. 

The carbamoyl phosphate then reacts with ornithine to start a cycle of reactions resulting in the production of urea (Fig. 9.12). 

The final reaction, like the previous one, is a simple hydrolysis. In this case arginase hydrolyses arginine to form urea plus ornithine. The ornithine formed is then available to react with more carbamoyl phosphate in the next turn of the cycle. Arginase is very active in mammalian liver. 

Carbamoyl phosphate reacts with the terminal amino group of ornithine in a nucleophilic acyl substitution reaction to give citrulline. 

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