Argininosuccinate, arginine from

Arginine synthetase yields one molecule of fumaric acid and one molecule of L-arginine from one molecule of argininosuccinic acid. 

The synthesis of arginine from citrulline involves the condensation of citrulline with aspartate to form argininosuccinate (S88, 437-441), in accordance with the following formulation ... 

The ability of the kidney to synthesize arginine from citralline was shown early on (Borsook and Dubnoff, 1941) which demonstrated that the cytosolic enzymes of the urea cycle, argininosuccinate... 

Arginine is synthesized from aspartate and ornithine during urea formation. Argininosuccinate synthetase and -lyase catalyze the condensation and cleavage reactions, respectively, that result in the formation of arginine (Sec. 15.5). 

The main reason is probably that the system evolved to keep the fumarate concentration low, because fumarate (and arginine) readily inhibits argininosuccinate lyase. Thus, this enzyme is cytoplasmic it is not inhibited by the high concentration of fumarate from the citric acid cycle since this fumarate is in the mitochondrion. 

Arginine and fumarate are produced from argininosuccinate by the cytosolic enzyme argininosuccinate lyase. In the final step of the cycle arginase cleaves urea from aspartate, regenerating cytosolic ornithine, which can be transported to the mitochondrial matrix for another round of urea synthesis. 

A. When argininosuccinate is cleaved to form arginine, the carbons that were derived from aspartate are released as fumarate and the nitrogen of aspartate is incorporated into arginine. 

Argininosuccinic aciduria results from a defective argininosuccinate lyase, mediating the cleavage of argininosuccinic acid to arginine and fumaric acid (Fig. 8). 

Protein Intake and Urea Excretion. Levin et al. (L7) were the first to show that urea excretion and therefore presumably urea synthesis was increased with increased protein intake in argininosuccinic aciduria. They showed in their patient that an increase of 2.5 times in the protein intake resulted in a 4- or 5-fold increase in urea output. From the results of a feeding trial, in which the infant was given a casein hydrolyzate from which most of the arginine had been removed, they concluded from the small amount of arginine present and the relatively high amount of urea excreted daily, that most of the urea was derived from a urea cycle, presumably in the liver. Conversely, reduction of protein intake resulted in a marked decrease in the output of both urea and argininosuccinic acid. 

Vidailhet et al. (VI) assayed all five enzymes involved in the urea cycle, and found no detectable activity of argininosuccinate synthetase, whereas the other enzymes were present in normal activity (Table 9). It is of interest that an appreciable synthetase activity was detectable in the kidney tissue in their patient, at a level of about 20% of that found in normal liver, despite its absence in the patient s liver (L4). This observation is similar to that of Colombo and Baumgartner (C8), who found argininosuccinate lyase in the kidney of their child with argininosuccinic aciduria, in spite of its absence from the liver. The question is again raised whether it is possible thus to account for the production of urea in these cases. However, since arginase is not present in the kidney, the arginine formed would have to be transported to the liver... 

The answer is e. (Murray, pp 505-626. Scriver, pp 4029-4240. Sack, pp 121-138. Wilson, pp 287-320.) All the compounds listed are intermediates of the citric acid cycle. However, only fumarate is an intermediate of both the citric acid and urea cycles. It and arginine are produced from argininosuccinate. Once produced by the urea cycle, fumarate enters the citric acid cycle and is converted to malate and then oxidized to oxaloacetate. Depending upon the organism s needs, oxaloacetate can either enter gluconeogenesis or react with acetyl CoA to form citrate. 

L-argininosuccinate from citrulline and L-aspartate in the arginine biosynthesis pathway potential Cdc28p substrate... 

Urea is synthesized in the liver in the urea cycle. The first step is formation of carbamoyl phosphate from ammonia, C02, and ATP. This is followed by a number of other steps, including formation of citrulline, argininosuccinate, and arginine, which is split to urea plus ornithine. The second nitrogen of urea is donated by aspartate in the formation of argininosuccinate. 

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