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The human arginases and arginase deficiency
R Iyer1, C P Jenkinson, J G Vockley
1Department of Pathology, University of California, Los Angeles, USA.
Journal of Inherited Metabolic Disease
|August 1, 1998
Summary
Arginase deficiency, a rare urea cycle disorder, primarily increases blood arginine. A second arginase enzyme, mainly in the kidney, can compensate for liver enzyme deficiency.
Area of Science:
- Biochemistry
- Genetics
- Metabolic Disorders
Background:
- Arginase is the terminal enzyme of the urea cycle.
- Arginase deficiency is a rare metabolic disorder, typically causing hyperargininemia.
- A second arginase locus (AII) in the kidney can compensate for liver arginase (AI) deficiency.
Purpose of the Study:
- Investigate the molecular pathology of arginase deficiency.
- Characterize the second arginase isoform (AII).
- Explore the evolutionary divergence and metabolic roles of arginase isoforms.
Main Methods:
- Studied liver arginase gene structure in patients.
- Cloned the second arginase isoform (AII) using conserved regions.
- Analyzed protein sequence conservation and localization.
- Compared arginase AI and AII across species.
Main Results:
- Identified molecular pathology in patients with arginase deficiency.
- Cloned and localized AII to mitochondria, implicating it in ornithine biosynthesis.
- Confirmed conserved protein sequences and structural features between AI and AII.
- AI and AII diverged before amphibian evolution.
- Presented evidence for AII's role in nitric oxide and polyamine metabolism.
Conclusions:
- Arginase deficiency's molecular basis can be studied via its gene structure.
- The kidney arginase isoform (AII) plays a significant role in compensating for liver arginase (AI) deficiency.
- AII is evolutionarily conserved and involved in critical metabolic pathways, including ornithine, nitric oxide, and polyamine synthesis.