Ames B N, Cathcart R, Schwiers E, Hochstein P
Proc Natl Acad Sci U S A. 1981 Nov;78(11):6858-62. doi: 10.1073/pnas.78.11.6858.
During primate evolution, a major factor in lengthening life-span and decreasing age-specific cancer rates may have been improved protective mechanisms against oxygen radicals. We propose that one of these protective systems is plasma uric acid, the level of which increased markedly during primate evolution as a consequence of a series of mutations. Uric acid is a powerful antioxidant and is a scavenger of singlet oxygen and radicals. We show that, at physiological concentrations, urate reduces the oxo-heme oxidant formed by peroxide reaction with hemoglobin, protects erythrocyte ghosts against lipid peroxidation, and protects erythrocytes from peroxidative damage leading to lysis. Urate is about as effective an antioxidant as ascorbate in these experiments. Urate is much more easily oxidized than deoxynucleosides by singlet oxygen and is destroyed by hydroxyl radicals at a comparable rate. The plasma urate levels in humans (about 300 microM) is considerably higher than the ascorbate level, making it one of the major antioxidants in humans. Previous work on urate reported in the literature supports our experiments and interpretations, although the findings were not discussed in a physiological context.
在灵长类动物的进化过程中，延长寿命和降低特定年龄癌症发病率的一个主要因素可能是针对氧自由基的保护机制得到了改善。我们提出，这些保护系统之一是血浆尿酸，由于一系列突变，其水平在灵长类动物进化过程中显著增加。尿酸是一种强大的抗氧化剂，是单线态氧和自由基的清除剂。我们发现，在生理浓度下，尿酸盐可减少过氧化物与血红蛋白反应形成的氧合血红素氧化剂，保护红细胞膜免受脂质过氧化，并保护红细胞免受导致溶血的过氧化损伤。在这些实验中，尿酸盐作为抗氧化剂的效果与抗坏血酸相当。尿酸盐比脱氧核苷更容易被单线态氧氧化，并且以相当的速率被羟基自由基破坏。人类血浆尿酸水平（约300微摩尔）远高于抗坏血酸水平，使其成为人类主要的抗氧化剂之一。文献中先前关于尿酸盐的研究支持了我们的实验和解释，尽管这些发现未在生理背景下进行讨论。
