THE HUMAN ARGINASES AND ARGINASE DEFICIENCY

Arginase is the final enzyme in the urea cycle. Its deficiency is the least frequently described disorder of this cycle. It results primaril y in elevated blood arginine, and less frequently in either persistent or acute elevations in blood ammonia. This appears to be due to a sec ond arginase locus, expressed primarily in the kidney, which can be re cruited to compensate, in part, for the deficiency of liver arginase. The liver arginase gene structure permitted study of the molecular pat hology of patients with the disorder and the results of these studies and the inferences about the protein structure are presented. The cons erved regions among all arginases allowed the cloning of AII, the seco nd arginase isoform. It has been localized to the mitochondrion and is thought to be involved in ornithine biosynthesis. It shares the major conserved protein sequences, and structural features of liver arginas e gene are also conserved. When AI and AII from various species are co mpared, it appears that the two diverged some time prior to the evolut ion of amphibians. The evidence for the role of AII in nitric oxide an d polyamine metabolism is presented and this appears consonant with th e data on the tissue distribution.