在原始人中，包括智人,尿酸是嘌呤分解代谢的最终产物。相比之下,其他胎盘哺乳动物通过尿酸氧化酶（尿酸酶）等酶将尿酸进一步降解为（S）-尿囊素，HIU水解酶（HIUase），和OHCU脱羧酶.一些生物，像青蛙和鱼，将（S）-尿囊素水解为尿囊酸，并最终水解为（S）-脲基乙醇酸酯和尿素，而海洋无脊椎动物将尿素转化为铵。在智人中，尿酸酶基因的突变导致选择压力降低，以维持编码嘌呤分解代谢途径其他酶的基因的完整性，导致尿酸积累。高尿酸血症,由于这种积累，与痛风有关,心血管疾病,糖尿病,和先兆子痫.许多常用的药物，比如阿司匹林,还可以增加尿酸水平。尽管在智人中明显不存在这些酶，似乎有尿酸酶(UOX)的转录本产生，HIUase(URAHP),OHCU脱羧酶（URAD），和尿囊酶(ALLC)。虽然一些URAHP转录本被归类为长链非编码RNA（lncRNAs），URAD和ALLC产生蛋白质编码转录物。鉴于这些转录本存在于各种组织中，我们假设它们可能在调节嘌呤分解代谢和高尿酸血症相关疾病的发病机制中起作用。在这里，我们对H.sapiens嘌呤分解代谢的独特方面进行了重点研究，尿酸酶基因突变的影响，以及相关转录本的潜在调节作用。这些发现为高尿酸血症及其相关疾病的研究和治疗方法开辟了新的途径。
In hominids, including Homo sapiens, uric acid is the end product of purine catabolism. In contrast, other placental mammals further degrade uric acid to (S)-allantoin by enzymes such as urate oxidase (uricase), HIU hydrolase (HIUase), and OHCU decarboxylase. Some organisms, such as frogs and fish, hydrolyze (S)-allantoin to allantoate and eventually to (S)-ureidoglycolate and urea, while marine invertebrates convert urea to ammonium. In H. sapiens, mutations in the uricase gene led to a reduction in the selective pressure for maintaining the integrity of the genes encoding the other enzymes of the purine catabolism pathway, resulting in an accumulation of uric acid. The hyperuricemia resulting from this accumulation is associated with gout, cardiovascular disease, diabetes, and preeclampsia. Many commonly used drugs, such as aspirin, can also increase uric acid levels. Despite the apparent absence of these enzymes in H. sapiens, there appears to be production of transcripts for uricase (UOX), HIUase (URAHP), OHCU decarboxylase (URAD), and allantoicase (ALLC). While some URAHP transcripts are classified as long non-coding RNAs (lncRNAs), URAD and ALLC produce protein-coding transcripts. Given the presence of these transcripts in various tissues, we hypothesized that they may play a role in the regulation of purine catabolism and the pathogenesis of diseases associated with hyperuricemia. Here, we specifically investigate the unique aspects of purine catabolism in H. sapiens, the effects mutations of the uricase gene, and the potential regulatory role of the corresponding transcripts. These findings open new avenues for research and therapeutic approaches for the treatment of hyperuricemia and related diseases.
