URIC-ACID, GOUT AND THE KIDNEY
URIC-ACID, GOUT AND THE KIDNEY
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DOI：
10.1136/jcp.34.11.1245
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发表时间：
1981-01-01
影响因子：
3.4
通讯作者：
SIMMONDS, HA
中科院分区：
文献类型：
--
作者：
CAMERON, JS;SIMMONDS, HA
尿酸是2，6，8-三羟基嘌呤，似乎存在于几乎所有的生物体中.在蛇、爬行动物、鸟类和蜘蛛中，尿酸是所有含氮代谢的主要终产物，这些动物的肾脏能够分泌大量的尿酸。然后以晶体浆的形式排出，这赋予了含氮最终产物可以用非常少的水排出的优点，这在干旱环境中是有益的。在哺乳动物中，尿酸是嘌呤代谢的唯一终产物，由嘌呤核苷酸分解而成，嘌呤核苷酸来源于DNA和RNA，也来源于其他对一般代谢起重要作用的化合物，如ATP、ADP、AMP、FAD、AMP、ADP、AMP、ADP、AMP、FAD、AMP、FAD、AMP、FAD、AMP、辅酶A和S-腺苷甲硫氨酸。在哺乳动物中，除了人类和近亲灵长类动物，尿酸被尿酸酶进一步分解为尿囊素。这样做的优点是尿囊素是一种非常可溶的化合物，而尿酸是非常不溶的。在生理pH值下，只有8位的羟基（pK为5 - 4）解离。因此，在血液和组织液中，尿酸绝大多数（98%）是游离形式的Ur-，因此在组织液中，有效的主要形式是Na+ Ur-，少量的K+ Uretc。相反，在尿中，由于pH的生理范围是4-7至8-0，HUr与Ur-的比例变化很大;在大多数酸性尿中，其形式主要是未解离的酸。它在水中的溶解度比尿酸钠低许多倍，因此不同pH值的尿液溶解尿酸的能力差异很大（图1）。尿酸的毒性和引起的病理变化完全是其不溶性的结果。如果不是因为灵长类动物也表现出的另一个特性，即肾小管会重吸收约90%的过滤后的尿酸盐，这一点可能并不那么重要，除非在酸性尿中有形成晶体或结石的倾向。不同哺乳动物的肾脏对尿液的处理有很大的差异
Uric acid is 2, 6, 8-trihydroxypurine, andseems to be present in almost all organisms. In snakes, reptiles, birds and spiders itis the main end-product of all nitrogenous metabolism, and these groups of animals have kidneys which are capable of secreting large amounts of uric acid. This is then excreted as a slurry of crystals, which confers the advantage that the nitrogenous end-product can be excreted with very little water, a benefit in arid environments. In contrast, the excretion of urea necessitates the loss of a relatively larger quantity of water, the size of which is dependent upon the concentrating ability of the kidney.In mammals, uric acid is the end-product only of purine metabolism and is formed by the breakdown of purine nucleotides, which are derived from DNA and RNA, and also from other compounds import-ant ingeneral metabolism, such as ATP, ADP and AMP, FAD, coenzyme A and S-adenosylmethionine. In mammals, with the exception of man and closely related primates, uric acidis further broken down to allantoin by the enzyme uricase. The advantage of this is that allantoin is a very soluble compound, whereas uricacid is very insoluble. At physiological pH only the hydroxyl group at the 8 position, which has a pK of 5 4, dissociates. Therefore, in blood and tissue fluids uric acid is overwhelmingly (98%) in the dissociatedform of Ur-, so that effectively in tissue fluids the predomin-ant form is Na+ Ur-, with smaller amounts of K+ Uretc. In the urine, in contrast, as the physiological range of pH is 4-7 to 8-0, the proportion of HUr to Ur-varies greatly; in most acid urines the form is predominantly the undissociated acid. Thisis many times less soluble in water than sodium urate, hence the great variation in the capacity of urine of various pHs to dissolve uric acid (Fig. 1). The toxicity of and the pathological changes caused by uric acid are entirely the consequences of its insolubility. This would not matter so much, except perhaps for a tendency to form crystals or stones in acid urine, were it not for one other peculiarity which primates also display, namely that the renal tubule reabsorbs around 90% of the filtered urate. There is great variation between different mammals in the renal handling of uric