ArticleNeurology. Genetics2016
Stabilization of the thermolabile variant S113L of carnitine palmitoyltransferase II.
Article in Neurology. Genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Mitochondrial carnitine palmitoyltransferase-II dysfunction: A possible novel mechanism for nonalcoholic fatty liver disease in hepatocarcinogenesis.World journal of gastroenterology · 2023Review
- Normal Thermostability of p.Ser113Leu and p.Arg631Cys Variants of Mitochondrial Carnitine Palmitoyltransferase II (CPT II) in Human Muscle Homogenate.Metabolites · 2022Article
- Cardiolipin Stabilizes and Increases Catalytic Efficiency of Carnitine Palmitoyltransferase II and Its Variants S113L, P50H, and Y479F.International journal of molecular sciences · 2021Article
- Rhabdomyolysis caused by carnitine palmitoyltransferase 2 deficiency: A case report and systematic review of the literature.Journal of the Intensive Care Society · 2020Review
- Muscle Carnitine Palmitoyltransferase II (CPT II) Deficiency: A Conceptual Approach.Molecules (Basel, Switzerland) · 2020Review
- Physiological aspects of muscular adaptations to training translated to neuromuscular diseases.Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2019Article
- Normal FGF-21-Serum Levels in Patients with Carnitine Palmitoyltransferase II (CPT II) Deficiency.International journal of molecular sciences · 2019Article
- Lack of activation of the S113L variant of carnitine palmitoyltransfersase II by cardiolipin.Journal of bioenergetics and biomembranes · 2018Article
- Muscle Carnitine Palmitoyltransferase II Deficiency: A Review of Enzymatic Controversy and Clinical Features.International journal of molecular sciences · 2017Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveMuscle carnitine palmitoyltransferase (CPT) II deficiency, the most common defect of lipid metabolism in muscle, is characterized by attacks of myoglobinuria without persistent muscle weakness.
methodsHis6-N-hCPT2 (wild-type) and His6-N-hCPT2/S113L (variant) were produced recombinantly in prokaryotic host and characterized according to their functional and regulatory properties.
resultsThe wild-type and the variant S113L showed the same enzymatic activity and thermostability at 30°C. The mutated enzyme, however, revealed an abnormal thermal destabilization at 40°C and 45°C. This was consistent with an increased flexibility (B-factor) of the variant at 40°C compared with that of the wild-type shown by molecular dynamics analysis. Preincubation of the enzymes with l-carnitine and acyl-l-carnitines containing more than 10 carbons in the acyl side-chain stabilized the mutated enzyme against thermal inactivation. In contrast, palmitoyl-CoA destabilized both enzymes.
conclusionsThe problems in CPT II deficiency originating from the S113L mutation are not caused by the loss of catalytically active enzyme. They might be at least partially related to an impaired thermal stability of the protein. The lower thermodynamic stability of the variant might explain why fever and prolonged exertion provoke attacks of myoglobinuria in CPT II deficiency. The stabilization by acyl-l-carnitines might provide the basis for possible preventive therapy of CPT II deficiency.
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Registered trials
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