Genetic, structural and biochemical basis of carbamoyl phosphate synthetase 1 deficiency

被引：54

作者：

Isabel Martinez, Ana ^{[1
]}

Perez-Arellano, Isabel ^{[1
,2
]}

Pekkala, Satu ^{[1
]}

Barcelona, Belen ^{[1
]}

Cervera, Javier ^{[1
,2
]}

机构：

[1] CIPF, Mol Recognit Lab, Valencia, Spain

[2] CIBERER ISCIII, Valencia, Spain

来源：

MOLECULAR GENETICS AND METABOLISM | 2010年 / 101卷 / 04期

关键词：

CPS1; deficiency; Hyperammonemia; Urea cycle; Inborn metabolic errors; Polymorphism; Mutation; SITE-DIRECTED MUTAGENESIS; RAT-LIVER MITOCHONDRIA; UREA CYCLE DISORDERS; ACETYL-L-GLUTAMATE; N-ACETYLGLUTAMATE SYNTHETASE; MULTIFUNCTIONAL PROTEIN CAD; COOH-TERMINAL DOMAIN; ESCHERICHIA-COLI; I DEFICIENCY; CARBAMYLPHOSPHATE SYNTHETASE;

D O I：

10.1016/j.ymgme.2010.08.002

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Carbamoyl phosphate synthetase 1 (CPS1) plays a paramount role in liver ureagenesis since it catalyzes the first and rate-limiting step of the urea cycle, the major pathway for nitrogen disposal in humans. CPS1 deficiency (CPS1D) is an autosomal recessive inborn error which leads to hyperammonemia due to mutations in the CPS1 gene, or is caused secondarily by lack of its allosteric activator NAG. Proteolytic, immunological and structural data indicate that human CPS1 resembles Escherichia coli CPS in structure, and a 3D model of CPS1 has been presented for elucidating the pathogenic role of missense mutations. Recent availability of CPS1 expression systems also can provide valuable tools for structure-function analysis and pathogenicity-testing of mutations in CPS1. In this paper, we provide a comprehensive compilation of clinical CPS1 mutations, and discuss how structural knowledge of CPS enzymes in combination with in vitro analyses can be a useful tool for diagnosis of CPS1D. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：311 / 323

页数：13

共 142 条

[1] Human carbamoyl-phosphate synthetase:: Insight into N-acetylglutamate interaction and the functional effects of a common single nucleotide polymorphism [J].