Nebraska Redox Biology Center Educational Portal

Uric Acid

Uric acid a product purine metabolisme in animals. Uric acid accumulates as its mono-anionic form, urate, at high concentrations in cells and extracellular fluids. Urate concentrations in human serum varies in range from 50 to 900 μM. Concentrations betwwen 200-300 μM are considered as normal and concentrations exceeding 420 μM are hyperuricemic [ 1, 2, 3 ].

The degradation of purines to urate is common to all animal species. Hovewer, in contrast to other mammals, in higher primates urate is considered the end product of purine metabolism because the urate-catabolizing enzyme, uricase, has been lost during primate evolution [ 4, 5, 6 ]. Uric acid is converted to allantoin by uricase in majority of mammals. In most fish and amphibians allantoin is degraded via allantoic acid by allantoinase and allantoicase to urea and glyoxylate. In some marine invertebrates and crustaceans, the urea formed is then hydrolysed to NH3 and CO2 by urease [ 6 ].

Route of purine degradation in animals [ 6 ].

The guanase and xanthine dehydrogenase/oxidase reactions. Guanase deaminates guanine to xanthine, which is again converted to uric acid by xanthine oxidase [ 7 ].

Non-primates uric acid mrtabolism [ 7 ].

Uric acid is known as scavenger of singlet oxygen, hydroperoxyl radicals and hydroxyl radicals. The ability of urate to scavenge oxygen radicals was originally proposed by Kellogg and Fridovich in 1977 [ 1, 7, 8, 9, 10 ]. Urate was proposed to be a one of the major antioxidants of the plasma that protects cells from oxidative damage, thereby contributing to an increase in life span of our species and decreasing the risk for cancer. Mechanisms of ureate antioxidant reaction are not well studied at this time [ 11 ]. The chemistry of urate oxidation by radicals is very complicated. Uric acid can form free radicals in different radical forming systems. Urate-derived radicals represent different degrees of degradation of the urate molecule, from the urate anion, in which the radical site is located on the five-membered ring of the purine structure, to carbon-centered radicals. Recent sudies demonstrated that ureate is a substrate for mieloperoxidases and lactoperoxidases [ 9 10 11 ].

Proposed reaction pathways for urate radicals that are formed when urate is oxidized by lactoperoxidase in presence of hydrogen peroxide [ 12 ].

The presence of ascorbic acid in the plasma is required for the antioxidant effect of uric acid [ 2, 13, 14 ]. Uric acid is a potent scavenger of peroxynitrite in the extracellular space, however, uric acid alone cannot scavenge superoxide, and the presence of ascorbic acid and thiols is absolutely required for scavenging of superoxide and peroxynitrite [ 13, 14 ]. Uric acid is a powerful scavenger of carbon-centered and hydroperoxyl radicals in the hydrophilic environment but is not able to scavenge lipophilic radicals and cannot stop the radical propagation within lipid membranes [ 14 ].

In addition to antioxidant function, uric acid can work as prooxidant and contribute in oxidative damage Reactions of uric acid with oxidants may also produce radicals that might propagate radical chain reaction. In addition, uric acid itself and related radicals can work as a biologically active proinflammatory factor, intracellular oxidant production via NADPH oxidase-dependent pathway resulting in redox-dependent intracellular signaling and oxidative stress [ 2, 9, 15 ].

Non-primates uric acid mrtabolism [ 11 ].

Futhermore, high level of uric acid is strongly associated and in many cases predicts development of hypertension [ 16 ], visceral obesity [ 17 ], insulin resistance [ 18 ], dyslipidemia [ 19 ], diabetes type 2 [ 18 ], kidney disease [ 20 ], and cardiovascular and cerebrovascular events [ 21 ].

Finally, antioxidant effect of uric acid was described only for hydrophilic environment and is not well studied. Reactions of uric acid with oxidants may also produce other radicals that might result in oxidative damage to cells. Exact role of uric acid in physiological and pathophysiological conditions as well as its role as antioxidant and prooxidant is not clear at this time.

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