The human arginases and arginase deficiency

Abstract

Arginase is the final enzyme in the urea cycle. Its deficiency is the least frequently described disorder of this cycle. It results primarily in elevated blood arginine, and less frequently in either persistent or acute elevations in blood ammonia. This appears to be due to a second arginase locus, expressed primarily in the kidney, which can be recruited to compensate, in part, for the deficiency of liver arginase. The liver arginase gene structure permitted study of the molecular pathology of patients with the disorder and the results of these studies and the inferences about the protein structure are presented. The conserved regions among all arginases allowed the cloning of AII, the second 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 arginase gene are also conserved. When AI and AII from various species are compared, it appears that the two diverged some time prior to the evolution of amphibians. The evidence for the role of AII in nitric oxide and polyamine metabolism is presented and this appears consonant with the data on the tissue distribution.

Visualizing the genome: techniques for presenting human genome data and annotations

“…Figure 4, a screen capture from the ProtAnnot prototype viewer, provides an example of how color can be used to indicate frame. In this case, alternative splicing at the ARG1 (arginase 1) locus [14] produces two distinct variants which differ at their 3' ends. The result is that the final exon in both variants is translated in two different frames, as can easily be seen by comparing their color.…”

Argininemia as a cause of severe chronic stunting in a low-resource developing country setting: a case report

“…The mainstay of treatment for argininemia is a protein-restricted diet [6]. This presents a substantial challenge in rural Guatemala, where poverty and food availability prevent many families from providing adequate nutrition for healthy children, much less for special needs diets.…”

Proof-of-Concept Gene Editing for the Murine Model of Inducible Arginase-1 Deficiency

“…Treatment of arginase-1 deficiency consists of supportive measures including pharmacologic agents to remove excess nitrogen and a low-protein diet. No cure is available 1, 2 , although liver transplantation restores liver arginase-1 and appears to prevent progression of the neurological symptoms 3 . We and others have previously generated and characterized similar tamoxifen-inducible mouse models of arginase-1 deficiency via Cre-mediated excision of Arg1 exons 7 and 8 that lead to mice nearly devoid of hepatic Arg1 enzyme activity with a severe wasting phenotype and death approximately two weeks later 4–6 .…”