Carbamoyl phosphate synthetase arginine biosynthesis

Dihydroorotate dehydrogenase, the enzyme catalyzing the dehydrogenation of dihydroorotate to orotate (reaction 4 of the pathway Fig. 15-15), is located on the outer side of the inner mitochondrial membrane. This enzyme has FAD as a prosthetic group and in mammals electrons are passed to ubiquinone. The de novo pyrimidine pathway is thus compartmentalized dihydroorotate synthesized by trifunctional DHO synthetase in the cytosol must pass across the outer mitochondrial membrane to be oxidized to orotate, which in turn passes back to the cytosol to be a substrate for bifunctional UMP synthase. Mammalian cells contain two carbamoyl phosphate synthetases the glutamine-dependent enzyme (CPSase II) which is part of CAD, and an ammonia-dependent enzyme (CPSase /) which is found in the mitochondrial matrix, and which is used for urea and arginine biosynthesis. Under certain conditions (e.g., hyperammonemia), carbamoyl phosphate synthesized in the matrix by CPSase I may enter pyrimidine biosynthesis in the cytosol. 

Mammalian cells contain two carbamoyl phosphate synthetases the glutamine-dependent enzyme (CPSase II) which is part of CAD and an ammonia-dependent enzyme (CPSase /) which is localized in the mitochondrial matrix and which is used in urea and arginine biosynthesis. Under certain conditions (e.g., hyperammonemia), carbamoyl phosphate synthesized in the matrix by CPSase I may enter pyrimidine biosynthesis in the cytoplasm. 

Birds appear unable to synthesise any arginine via the urea cycle (see Section 5.4), which may be because of lack of carbamoyl phosphate synthetase I in mitochondria (Baker, 1991), and, as a result, the dietary requirement for arginine is higher than in growing mammals. However, they do appear to have a carbamoyl phosphate synthetase II in the cytosol (Maresh, Kwan Kalman, 1969). This may be part of the multienzyme protein G D (carbamoyl phosphate synthase-aspartate carbamoyl transferase-dihydroorotase), responsible for the biosynthesis of 3ihydroorotate, a pyrimidine precursor, but this is bound on the multienzyme protein, and it seems unlikely that it would be available for arginine biosynthesis (see Price Stevens, 1989). 

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