Figure 2. Antioxidant and pro-oxidant effect of uric acid.

Antioxidant activities. (A) Peroxynitrites (ONOO^–) are produced from the reaction of nitric oxide (NO•) with superoxide (O2^–•). Peroxynitrites can induce protein nitrosation and lipid and protein peroxidation and block tetrahydrobiopterin (HB4), a cofactor necessary for NOS activity. In the absence of HB4, NOS produces ROS. Uric acid (UA) can directly inactivate peroxynitrite by a reaction that generates uric acid radicals (UA•); these can be rapidly eliminated by plasma ascorbic acid. (B) Uric acid can also prevent Cu²⁺-induced oxidation of LDL, a reaction that may protect against atherosclerosis development. (C) By enhancing arginase activity, uric acid diverts l-arginine from NO production to urea production. Uric acid can also directly react with NO to generate nitrosated uric acid, and the nitroso group can then be transferred to glutathione (GSH) for transport to another recipient molecule. In the presence of oxygen, uric acid reacts with NO to produce the stable species 6-aminouracil. Uric acid uptake in adipocytes activates NADPH oxidase and increase production of ROS, which can initiate an inflammatory reaction. In vascular smooth muscle cells, uric acid can activate the NF-κB and MAPK pathway and increase cyclooxygenase and MCP-1 production. Blue arrows, chemical reactions; green arrows, products from enzymatic or signaling pathways; red arrows, activation of enzymatic activities.