Biochemistry, pharmacology and

Area of Science:

• Biochemistry and Molecular Biology
• Physiology
• Pharmacology

Background:

• Arginase catalyzes L-arginine hydrolysis into L-ornithine and urea, with two isoforms, Arg1 and Arg2.
• Arginase is vital for nitrogen detoxification, polyamine synthesis, and regulating L-arginine and nitric oxide (NO).
• Despite known functions, significant questions remain regarding arginase regulation and roles.

Purpose of the Study:

• To critically review the biochemistry, pharmacology, and in vivo functions of arginases.
• To highlight cell-type-specific and species-specific differences between Arg1 and Arg2.
• To discuss insights from knockout mouse models and human studies with arginase inhibitors.

Main Methods:

• Review of existing literature on arginase biochemistry and function.
• Analysis of data from cell-specific Arg1 and Arg2 knockout mice.
• Examination of human studies involving arginase inhibitors and pegylated recombinant arginase.

Main Results:

• Arg1 and Arg2 exhibit distinct cellular localizations and functions, differing significantly between mice and humans, especially in immune and erythroid cells.
• Arg1's role in vascular NO signaling is context-dependent, increasing under disease conditions.
• Arg2 primarily functions in L-ornithine, polyamine, and proline synthesis, with a potential role in blood pressure regulation (mice).

Conclusions:

• Further research is needed to elucidate Arg1 and Arg2 regulation, localization, and species-specific roles.
• A deeper understanding will enable improved pharmacological strategies targeting arginase for liver, cardiovascular, hematological, immune diseases, and cancer.
• The immunosuppressive function of arginase offers a promising avenue for cancer treatment development.