ArticleThe Biochemical journal2007
Kinetic properties of mutant deoxyguanosine kinase in a case of reversible hepatic mtDNA depletion.
Article in The Biochemical journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 51 citations in OpenAlex.
- Deoxyguanosine kinase deficiency couples purine metabolism to innate immune activation and lipid accumulation in hepatocytes.Frontiers in immunology · 2026Article
- Deoxyguanosine kinase deficiency: natural history and liver transplant outcome.Brain communications · 2024Article
- Deoxyguanosine kinase mutation F180S is associated with a lean phenotype in mice.International journal of obesity (2005) · 2023Article
- Case report: NovelFrontiers in pediatrics · 2023Article
- A Combined Model of Human iPSC-Derived Liver Organoids and Hepatocytes Reveals Ferroptosis in DGUOK Mutant mtDNA Depletion Syndrome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- [DGUOK-related mitochondrial DNA depletion syndrome: a case report and literature review].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2020Review
- Molecular regulation of high muscle mass in developing Blonde d'Aquitaine cattle foetuses.Biology open · 2017Article
- A fatal case of mitochondrial DNA depletion syndrome with novel compound heterozygous variants in the deoxyguanosine kinase gene.Oncotarget · 2017Article
- Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology (Baltimore, Md.) · 2016Article
- Potentially diagnostic electron paramagnetic resonance spectra elucidate the underlying mechanism of mitochondrial dysfunction in the deoxyguanosine kinase deficient rat model of a genetic mitochondrial DNA depletion syndrome.Free radical biology & medicine · 2016Article
- Article
- Reduced mitochondrial DNA content and heterozygous nuclear gene mutations in patients with acute liver failure.Journal of pediatric gastroenterology and nutrition · 2013Article
- Gastrointestinal and hepatic manifestations of mitochondrial disorders.Journal of inherited metabolic disease · 2013Review
- Mitochondrial DNA depletion syndromes: review and updates of genetic basis, manifestations, and therapeutic options.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2013Review
- Next-generation sequencing reveals DGUOK mutations in adult patients with mitochondrial DNA multiple deletions.Brain : a journal of neurology · 2012Article
- A novel variation in the Twinkle linker region causing late-onset dementia.Neurogenetics · 2010Article
- Mitochondrial mosaics in the liver of 3 infants with mtDNA defects.BMC clinical pathology · 2009Article
- Altered gene transcription profiles in fibroblasts harboring either TK2 or DGUOK mutations indicate compensatory mechanisms.Experimental cell research · 2009Article
- Non-homologous recombination of deoxyribonucleoside kinases from human and Drosophila melanogaster yields human-like enzymes with novel activities.Journal of molecular biology · 2007Article
- Defects in mitochondrial DNA replication and human disease.Critical reviews in biochemistry and molecular biologyReview
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DGUOK [dG (deoxyguanosine) kinase] is one of the two mitochondrial deoxynucleoside salvage pathway enzymes involved in precursor synthesis for mtDNA (mitochondrial DNA) replication. DGUOK is responsible for the initial rate-limiting phosphorylation of the purine deoxynucleosides, using a nucleoside triphosphate as phosphate donor. Mutations in the DGUOK gene are associated with the hepato-specific and hepatocerebral forms of MDS (mtDNA depletion syndrome). We identified two missense mutations (N46S and L266R) in the DGUOK gene of a previously reported child, now 10 years old, who presented with an unusual revertant phenotype of liver MDS. The kinetic properties of normal and mutant DGUOK were studied in mitochondrial preparations from cultured skin fibroblasts, using an optimized methodology. The N46S/L266R DGUOK showed 14 and 10% residual activity as compared with controls with dG and deoxyadenosine as phosphate acceptors respectively. Similar apparent negative co-operativity in the binding of the phosphate acceptors to the wild-type enzyme was found for the mutant. In contrast, abnormal bimodal kinetics were shown with ATP as the phosphate donor, suggesting an impairment of the ATP binding mode at the phosphate donor site. No kinetic behaviours were found for two other patients with splicing defects or premature stop codon. The present study represents the first characterization of the enzymatic kinetic properties of normal and mutant DGUOK in organello and our optimized protocol allowed us to demonstrate a residual activity in skin fibroblast mitochondria from a patient with a revertant phenotype of MDS. The residual DGUOK activity may play a crucial role in the phenotype reversal.
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