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大鼠肝脏上清液由嘌呤碱、核苷和核苷酸合成尿酸。别嘌呤醇的作用。

Uric acid synthesis by rat liver supernatants from purine bases, nucleosides and nucleotides. Effect of allopurinol.

作者信息

Bleisch S, Sillero M A, Torrecilla A, Sillero A

机构信息

Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.

出版信息

Cell Biochem Funct. 1994 Dec;12(4):237-45. doi: 10.1002/cbf.290120403.

DOI:10.1002/cbf.290120403
PMID:7834812
Abstract

The synthesis of uric acid from purine bases, nucleosides and nucleotides has been measured in reaction mixtures containing rat liver supernatant and each one of the following compounds at 1 mM concentration (except xanthine, 0.5 mM and guanosine and guanine, 0.1 mM). The rates of the reaction, expressed as nanomoles of uric acid synthesized g-1 of wet liver min-1 were: ATP, 10; ADP, 37; AMP, 62; adenosine, 108; adenine 6; adenylosuccinate, 9; IMP 32; inosine, 112; hypoxanthine, 50; GTP, 19; GDP, 19; GMP, 27; guanosine, 34; guanine, 72; XMP, 10; xanthosine, 24; xanthine, 144. These figures divided by 55 correspond to nanomoles of uric acid synthesized min-1 per mg-1 of protein. The rate of synthesis of uric acid obtained with each one of those compounds at 0.1 and 0.05 mM concentrations was also determined. ATP (1 mM) strongly inhibited uric acid synthesis from 0.05 mM AMP (91 per cent) and from 0.05 mM ADP (88 per cent), but not from adenosine. CTP or UTP (1 mM) also inhibited (by more than 90 per cent) the synthesis of uric acid from 0.05 mM AMP. Xanthine oxidase was inhibited by concentrations of hypoxanthine higher than 0.012 mM. The results favour the view that the level of uric acid in plasma may be an index of the energetic state of the organism. Allopurinol, besides inhibiting uric acid synthesis, reduced the rate of degradation of AMP. The ability of crude extracts to catabolize purine nucleotides to uric acid is an important factor to be considered when some enzymes related to purine nucleotide metabolism, particularly CTP synthase, are measured in crude liver extracts.

摘要

在含有大鼠肝脏上清液以及以下各化合物(浓度均为1 mM,但黄嘌呤为0.5 mM,鸟苷和鸟嘌呤为0.1 mM)的反应混合物中,已对由嘌呤碱、核苷和核苷酸合成尿酸的过程进行了测定。反应速率以每克湿肝脏每分钟合成尿酸的纳摩尔数表示,结果如下:ATP,10;ADP,37;AMP,62;腺苷,108;腺嘌呤,6;腺苷酸琥珀酸,9;IMP,32;肌苷,112;次黄嘌呤,50;GTP,19;GDP,19;GMP,27;鸟苷,34;鸟嘌呤,72;XMP,10;黄苷,24;黄嘌呤,144。这些数值除以55后即相当于每毫克蛋白质每分钟合成尿酸的纳摩尔数。还测定了上述各化合物在0.1 mM和0.05 mM浓度下合成尿酸的速率。ATP(1 mM)强烈抑制由0.05 mM AMP(91%)和0.05 mM ADP(88%)合成尿酸,但对腺苷合成尿酸无抑制作用。CTP或UTP(1 mM)也抑制(超过90%)由0.05 mM AMP合成尿酸。当次黄嘌呤浓度高于0.012 mM时,黄嘌呤氧化酶受到抑制。这些结果支持血浆中尿酸水平可能是机体能量状态指标的观点。别嘌呤醇除了抑制尿酸合成外,还降低了AMP的降解速率。在粗制肝脏提取物中测定某些与嘌呤核苷酸代谢相关的酶(尤其是CTP合酶)时,粗提物将嘌呤核苷酸分解代谢为尿酸的能力是一个需要考虑的重要因素。

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