Argininosuccinate lyase deficiency-argininosuccinic aciduria and beyond.
Argininosuccinate lyase deficiency-argininosuccinic aciduria and beyond.
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DOI：
10.1002/ajmg.c.30289
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发表时间：
2011-02-15
影响因子：
3.1
通讯作者：
Lee, Brendan
中科院分区：
文献类型：
--
作者：
Erez, Ayelet;Nagamani, Sandesh C. Sreenath;Lee, Brendan
尿素循环由六个连续的酶反应组成，将废氮转化为尿素。任何这些循环酶的缺乏都会导致尿素循环障碍（UCD），这是一组先天性的肝脏代谢错误，通常会导致危及生命的高氨血症。精氨基琥珀酸裂解酶 (ASL) 是一种胞质酶，催化循环中的第四个反应和第一个降解步骤，即将精氨基琥珀酸分解为精氨酸和富马酸。 ASL 缺乏会导致精氨基琥珀酸在组织中积聚，并通过尿液排泄精氨基琥珀酸，从而导致精氨基琥珀酸尿症 (ASA)。 ASA 是一种常染色体隐性遗传疾病，是第二常见的尿素循环障碍。除了精氨基琥珀酸的积累之外，ASL 缺乏还会导致精氨酸合成减少，这与除精氨酸血症外的所有 UCD 一样。精氨酸不仅是尿素循环中合成尿素和鸟氨酸的前体，而且是合成一氧化氮、多胺、脯氨酸、谷氨酸、肌酸和胍丁胺的底物。因此，虽然 ASL 是体内唯一能够产生精氨酸的酶，但至少有四种酶使用精氨酸作为底物：精氨酸脱羧酶、精氨酸酶、一氧化氮合成酶 (NOS) 和精氨酸/甘氨酸转氨酶。在肝脏中，ASL的主要功能是尿素生成，因此没有精氨酸的净合成。相反，在大多数其他组织中，它的作用是产生精氨酸，以满足特定细胞的需求。虽然 ASA 患者具有其他 UCD 常见的高氨血症、脑病和呼吸性碱中毒的急性临床表型，但他们还表现出独特的慢性并发症，最有可能是由组织特异性精氨酸缺乏和/或精氨基琥珀酸升高引起的。这篇综述文章总结了这种疾病的临床特征、生化、酶学和分子特征。讨论了当前的治疗、产前诊断、新生儿筛查诊断以及假设驱动的未来治疗方式。
The urea cycle consists of six consecutive enzymatic reactions that convert waste nitrogen into urea. Deficiencies of any of these enzymes of the cycle result in urea cycle disorders (UCD), a group of inborn errors of hepatic metabolism that often result in life threatening hyperammonemia. Argininosuccinate Lyase (ASL) is a cytosolic enzyme which catalyzes the fourth reaction in the cycle and the first degradative step, i.e. the breakdown of argininosuccinic acid to arginine and fumarate. Deficiency of ASL results in an accumulation of argininosuccinic acid in tissues, and excretion of argininosuccinic acid in urine leading to the condition argininosuccinic aciduria, ASA. ASA is an autosomal recessive disorder and is the second most common urea cycle disorder. In addition to the accumulation of argininosuccinic acid, ASL deficiency results in decreased synthesis of arginine which is in common with all UCDs except argininemia. Arginine is not only the precursor for the synthesis of urea and ornithine as part of the urea cycle but it is also the substrate for the synthesis of nitric oxide, polyamines, proline, glutamate, creatine and agmatine. Hence, while ASL is the only enzyme in the body able to generate arginine, at least four enzymes use arginine as substrate: arginine decarboxylase, arginase, nitric oxide synthetase (NOS) and arginine/glycine aminotransferase. In the liver, the main function of ASL is ureagenesis, and hence, there is no net synthesis of arginine. In contrast, in most other tissues, its role is to generate arginine that is designated for the specific cell’s needs. While patients with ASA share the acute clinical phenotype of hyperammonemia, encephalopathy and respiratory alkalosis common to other UCD, they also present with unique chronic complications most probably caused by a combination of tissue specific deficiency of arginine and/or elevation of argininosuccinic acid. This review article summarizes the clinical characterization, biochemical, enzymatic, and molecular features of this disorder. Current treatment, prenatal diagnosis, diagnosis through the newborn screening as well as hypothesis driven future treatment modalities are discussed.
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影响因子：
5.1
作者：
Batshaw, ML;MacArthur, RB;Tuchman, M
通讯作者：
Tuchman, M
影响因子：
158.5
作者：
BATSHAW, ML;BRUSILOW, S;SCHAFER, IA
通讯作者：
SCHAFER, IA
DOI：
10.1016/s0006-291x(64)80001-2
发表时间：
1964-01-01
影响因子：
3.1
作者：
CORYELL, ME;HORTON, BF;THEVAOS, TG
通讯作者：
THEVAOS, TG
影响因子：
4.2
作者：
DONN, SM;THOENE, JG
通讯作者：
THOENE, JG
影响因子：
1.4
作者：
GERRITS, GPJM;GABREELS, FJM;TRIJBELS, JMF
通讯作者：
TRIJBELS, JMF