'Late onset' ornithine transcarbamylase deficiency: function of three purified recombinant mutant enzymes

Human Molecular Genetics
H MorizonoM Tuchman

Abstract

Although many mutations in the ornithine transcarbamylase gene have been correlated with 'late onset' of hyperammonemia in patients, the effects of these mutations on enzyme function are largely unknown. Three recurrent mutations (R40H, R277W and R277Q) found in patients with 'late onset' disease were incorporated into 'mature' human ornithine transcarbamylase cDNA and overexpressed in Escherichia coli. The three recombinant mutant enzymes were purified to homogeneity on an affinity column and their biochemical characteristics were compared to the wild type enzyme. The R277W and R277Q mutants display markedly reduced affinity for L-ornithine, loss of substrate inhibition, alkaline shift of pH optimum, and reduced thermal stability compared to the wild type enzyme. These differences, particularly the reduced affinity for L-ornithine, are sufficient to account for their biochemical effects. In contrast, the 'mature' R40H mutant was biochemically indistinguishable from the wild type enzyme in vitro.

References

Dec 1, 1990·The Journal of Pediatrics·J E FinkelsteinS W Brusilow
Jan 1, 1982·Methods in Enzymology·K J Ellis, J F Morrison
Dec 1, 1981·Analytical Biochemistry·S C Pastra-LandisE R Kantrowitz
Nov 7, 1995·Proceedings of the National Academy of Sciences of the United States of America·V VilleretO Dideberg
Feb 1, 1995·Human Genetics·E O Oppliger LeibundgutB Wermuth
Jan 1, 1994·Human Mutation·M TuchmanA A Qureshi
Jul 15, 1996·European Journal of Biochemistry·G ValentiniP Iadarola

❮ Previous
Next ❯

Citations

Sep 2, 1997·Proceedings of the National Academy of Sciences of the United States of America·Y HaN M Allewell
Jun 11, 2015·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Ljubica CaldovicHiroki Morizono
Apr 26, 2006·Pediatrics International : Official Journal of the Japan Pediatric Society·Eimei HaradaMakoto Yoshino
May 19, 2018·Pediatric Blood & Cancer·Megan PetersJessica Scott Schwoerer
Aug 1, 1998·Journal of Inherited Metabolic Disease·M TuchmanN M Allewell
Jan 17, 2002·Human Mutation·Mendel TuchmanMichael G Lynch

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.