Molecular Structure, Metabolic Pathways and Clinical Relevance of Arginase: A Review

Arginase is an essential enzyme catalyzing the L-arginine hydrolysis to L-ornithine and urea, fundamental to the urea cycle in mammals. The isoforms, arginase I, mainly hepatic and cytosolic, critical for detoxifying ammonia and arginase II, mitochondrial and more widespread across tissues. This review investigates the significance of arginase, especially arginase I, in liver function, highlighting its role in converting toxic ammonia into urea. Understanding the enzyme’s structure, including its binuclear manganese cluster and trimeric formation, is crucial for insights into its catalytic mechanism and possible therapeutic targets. Research on liver arginase spans decades, initially focusing on its biochemical properties and now exploring its regulatory mechanisms and clinical implications in diseases like cardiovascular disorders, diabetes and cancer. Arginase activity influences metabolic pathways, impacting nitric oxide production, insulin sensitivity and lipid metabolism. Dysregulation of arginase leads to hypertension, diabetes and hepatic steatosis, making it a promising target for therapeutic interventions. Technological advancements like X-ray crystallography, cryo-electron microscopy and computational modeling have elucidated the detailed structure of arginase, revealing its catalytic sites and potential for drug binding. These studies are pivotal for developing arginase inhibitors, which have shown promise in improving endothelial function and glucose metabolism in clinical settings. Overall, this review underscores the multifaceted role of liver arginase in metabolic processes and disease, advocating for continued research to fully harness its therapeutic potential.