Johnson Richard J, Sautin Yuri Y, Oliver William J, Roncal Carlos, Mu Wei, Gabriela Sanchez-Lozada L, Rodriguez-Iturbe Bernardo, Nakagawa Takahiko, Benner Steven A
Division of Nephrology, Hypertension and Transplantation, University of Florida, Gainesville, FL 32610, USA.
J Comp Physiol B. 2009 Jan;179(1):67-76. doi: 10.1007/s00360-008-0291-7. Epub 2008 Jul 23.
Uric acid has historically been viewed as a purine metabolic waste product excreted by the kidney and gut that is relatively unimportant other than its penchant to crystallize in joints to cause the disease gout. In recent years, however, there has been the realization that uric acid is not biologically inert but may have a wide range of actions, including being both a pro- and anti-oxidant, a neurostimulant, and an inducer of inflammation and activator of the innate immune response. In this paper, we present the hypothesis that uric acid has a key role in the foraging response associated with starvation and fasting. We further suggest that there is a complex interplay between fructose, uric acid and vitamin C, with fructose and uric acid stimulating the foraging response and vitamin C countering this response. Finally, we suggest that the mutations in ascorbate synthesis and uricase that characterized early primate evolution were likely in response to the need to stimulate the foraging "survival" response and might have inadvertently had a role in accelerating the development of bipedal locomotion and intellectual development. Unfortunately, due to marked changes in the diet, resulting in dramatic increases in fructose- and purine-rich foods, these identical genotypic changes may be largely responsible for the epidemic of obesity, diabetes and cardiovascular disease in today's society.
尿酸在历史上一直被视为一种嘌呤代谢废物，由肾脏和肠道排出，除了倾向于在关节中结晶导致痛风外，相对来说并不重要。然而，近年来人们认识到尿酸并非生物惰性物质，而是可能具有广泛的作用，包括既是促氧化剂又是抗氧化剂、神经刺激剂、炎症诱导剂以及先天免疫反应的激活剂。在本文中，我们提出一个假说，即尿酸在与饥饿和禁食相关的觅食反应中起关键作用。我们进一步认为，果糖、尿酸和维生素C之间存在复杂的相互作用，果糖和尿酸刺激觅食反应，而维生素C则对抗这种反应。最后，我们认为早期灵长类动物进化过程中表征的抗坏血酸合成和尿酸酶突变，可能是为了响应刺激觅食“生存”反应的需要，并且可能在无意中对加速双足运动和智力发展起到了作用。不幸的是，由于饮食的显著变化，导致富含果糖和嘌呤的食物大幅增加，这些相同的基因型变化可能在很大程度上导致了当今社会肥胖、糖尿病和心血管疾病的流行。
