Human arginase isozymes.

Area of Science:

• Biochemistry
• Molecular Biology
• Human Physiology

Background:

• Two arginase isozymes, AI (high pI, cytosolic) and AII (neutral pI, mitochondrial), have been identified in humans and experimental animals.
• Arginase AI is predominantly found in the liver and is crucial for ammonia detoxification into urea.
• Arginase AII is widely expressed and involved in ornithine production for proline and glutamate synthesis.

Purpose of the Study:

• To elucidate the distinct roles and characteristics of the two identified arginase isozymes.
• To understand the genetic basis of hyperargininemia related to arginase AI.
• To differentiate the immunological and genetic properties of arginase AI and AII.

Main Methods:

• Comparative analysis of arginase isozyme properties in experimental animals and humans.
• Investigation of the gene mutation responsible for human hyperargininemia.
• Immunological assays to assess distinctness between isozymes.
• DNA cross-hybridization studies to evaluate genetic differences.

Main Results:

• Arginase AI is primarily involved in ammonia detoxification, with mutations causing hyperargininemia.
• Arginase AII is implicated in ornithine production, serving as a precursor for proline and glutamate.
• Both isozymes are encoded by separate genes and are immunologically distinct.
• Despite kinetic similarities, significant compositional differences exist between AI and AII.

Conclusions:

• The human body possesses two distinct arginase isozymes with specialized functions: AI for ammonia detoxification and AII for ornithine production.
• Genetic defects in arginase AI lead to hyperargininemia, highlighting its critical role in urea cycle.
• The immunological and genetic distinctness of arginase AI and AII underscore their separate evolutionary and functional pathways.