Arginase in glomerulonephritis.
l-Arginine is converted to nitric oxide and citrulline by the enzyme nitric oxide synthase (NOS). Its in vivo inhibition has led to the revelation of a multitude of diverse, often conflicting functions in the inflammatory melee. l-Arginine is also converted to ornithine and urea by the enzyme arginase as a part of the hepatic urea cycle. However, a more holistic interpretation of the two pathways and the associated metabolism (summarized in Fig. 1) has led to its reassessment as a pathologically significant enzyme. This is reflected by the continued increase over the past five years of the number of publications discussing both nitric oxide and arginase. The strong association between inflammation and high arginase and NOS activity is epitomized by immune complex-induced glomerulonephritis and other glomerulonephritides. Arginase is encoded by two recently discovered genes (Arginase I and Arginase II). There is now substantial evidence for an interaction between both arginase isoforms and all three NOS isoforms in pathological situations. This review considers the relationship between Arginases I and II and the inflammation-associated isoform of NOS called NOS II. In particular, it consolidates the current understanding of arginase and associated metabolic pathways, and highlights some of the issues that are often overlooked in such studies.
Waddington
Simon N
SN
Gene Therapy Group, Section of Cell and Molecular Biology, Faculty of Medicine, Imperial College School of Science Technology and Medicine, Sir Alexander Fleming Building, Imperial College Road, London, England SW7 2AZ, UK. s.waddington@ic.ac.uk
D000818:Animals; D001119:Arginase / Q000378:metabolism / Q000502:physiology*; D001120:Arginine / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005921:Glomerulonephritis / Q000503:physiopathology*; D006801:Humans; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D015854:Up-Regulation
D004791:Enzyme Inhibitors; D001120:Arginine; D019001:Nitric Oxide Synthase; D001119:Arginase