Synthesis of guanidinosuccinate from argininosuccinate and reactive oxygen in vitro.

Enzyme & protein Pub Date : 1996-01-01 DOI:10.1159/000468629
K Aoyagi, S Nagase, C Tomida, K Takemura, K Akiyama, A Koyama
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引用次数: 18

Abstract

Synthesis of guanidinosuccinic acid (GSA), a uremic toxin, has been suggested to relate to the urea concentration and synthetic rate. Among the urea cycle enzymes, inhibition of argininosuccinate (ASA) lyase by urea has been reported. Argininosuccinate which contains a GSA structure is a candidate of a GSA precursor. We found that another uremic toxin, methylguanidine, is formed from creatinine with reactive oxygen species. Therefore, we investigated in vitro whether GSA is formed from ASA with reactive oxygen species. GSA was measured by HPLC by a post-column-labeling method using 9,10-phenathrequinone. When 1 mmol/l ASA was reacted with the hydroxyl radical-generating system for 5 min at pH 7.4, 9 mumol/l GSA was formed. Dimethylsulfoxide, a hydroxyl radical scavenger, markedly inhibited GSA synthesis. The superoxide radical generated by xanthine and xanthine oxidase reaction also formed 1 mumol/l GSA from 1 mumol/l ASA and the GSA formation was inhibited by superoxide dismutase or catalase almost completely. Addition of FeCl2 to the xanthine/xanthine oxidase reaction further increased GSA synthesis. These results indicate that GSA is formed from ASA by reaction with the hydroxyl radical and the superoxide radical.

精氨酸琥珀酸盐与活性氧体外合成胍基琥珀酸盐。
胍丁二酸(GSA)是一种尿毒症毒素,其合成与尿素浓度和合成速率有关。在尿素循环酶中,尿素对精氨酸琥珀酸(ASA)裂解酶有抑制作用。含有GSA结构的精氨酸琥珀酸盐是GSA前体的候选物。我们发现另一种尿毒症毒素,甲基胍,是由肌酸酐与活性氧形成的。因此,我们在体外研究了GSA是否由ASA与活性氧形成。采用柱后标记法,用9,10-吩喹诺酮测定GSA。1 mmol/l的ASA与羟基自由基生成系统在pH 7.4条件下反应5 min,生成9 μ mol/l的GSA。二甲基亚砜是一种羟基自由基清除剂,能显著抑制GSA的合成。黄嘌呤与黄嘌呤氧化酶反应产生的超氧化物自由基也由1 μ mol/l的ASA生成1 μ mol/l的GSA,且GSA的生成几乎完全被超氧化物歧化酶或过氧化氢酶抑制。在黄嘌呤/黄嘌呤氧化酶反应中加入FeCl2进一步增加了GSA的合成。这些结果表明,GSA是由ASA与羟基自由基和超氧自由基反应生成的。
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