Recurrence of carbamoyl phosphate synthetase 1 (CPS1) deficiency in Turkish patients: characterization of a founder mutation by use of recombinant CPS1 from insect cells expression

Molecular Genetics and Metabolism
Liyan HuJohannes Häberle

Abstract

Carbamoyl phosphate synthetase 1 (CPS1) deficiency due to CPS1 mutations is a rare autosomal-recessive urea cycle disorder causing hyperammonemia that can lead to death or severe neurological impairment. CPS1 catalyzes carbamoyl phosphate formation from ammonia, bicarbonate and two molecules of ATP, and requires the allosteric activator N-acetyl-L-glutamate. Clinical mutations occur in the entire CPS1 coding region, but mainly in single families, with little recurrence. We characterized here the only currently known recurrent CPS1 mutation, p.Val1013del, found in eleven unrelated patients of Turkish descent using recombinant His-tagged wild type or mutant CPS1 expressed in baculovirus/insect cell system. The global CPS1 reaction and the ATPase and ATP synthesis partial reactions that reflect, respectively, the bicarbonate and the carbamate phosphorylation steps, were assayed. We found that CPS1 wild type and V1013del mutant showed comparable expression levels and purity but the mutant CPS1 exhibited no significant residual activities. In the CPS1 structural model, V1013 belongs to a highly hydrophobic β-strand at the middle of the central β-sheet of the A subdomain of the carbamate phosphorylation domain and is close to the pre...Continue Reading

References

Feb 22, 1990·European Journal of Biochemistry·H G BrittonV Rubio
Oct 16, 2002·Biochemistry·Jungwook KimFrank M Raushel
Apr 15, 2004·Archives of Biochemistry and Biophysics·Jungwook Kim, Frank M Raushel
Aug 11, 2004·Analytical Biochemistry·Mei-Chu LoGeorge Ellestad
Apr 7, 2009·Molecular Genetics and Metabolism·Meaghan Anne NeillMarshall L Summar
Mar 12, 2010·Molecular Genetics and Metabolism·D S FroeseR A Gravel
Aug 31, 2010·Molecular Genetics and Metabolism·Ana Isabel MartínezJavier Cervera
Sep 22, 2010·Molecular Genetics and Metabolism·Jing WangLee-Jun C Wong
May 12, 2012·Molecular Genetics and Metabolism·Rita KretzJohannes Häberle
Aug 27, 2013·Molecular Genetics and Metabolism·Marshall L SummarBrian Kirmse

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Citations

Feb 26, 2016·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Carmen Diez-FernandezJohannes Häberle

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