Next Article in Journal
rs657075 (CSF2) Is Associated with the Disease Phenotype (BAS-G) of Ankylosing Spondylitis
Previous Article in Journal
Somatic Genetic Variation in Solid Pseudopapillary Tumor of the Pancreas by Whole Exome Sequencing
Previous Article in Special Issue
Glucose-6-Phosphate Dehydrogenase: Update and Analysis of New Mutations around the World
Article Menu
Issue 1 (January) cover image

Export Article

Open AccessReview
Int. J. Mol. Sci. 2017, 18(1), 82; doi:10.3390/ijms18010082

Muscle Carnitine Palmitoyltransferase II Deficiency: A Review of Enzymatic Controversy and Clinical Features

1
Department of Neurology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle/Saale, Germany
2
Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Halle (Saale), Wolfgang-Langenbeck-Str. 4, 06120 Halle/Saale, Germany
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Christo Z. Christov
Received: 31 October 2016 / Revised: 20 December 2016 / Accepted: 28 December 2016 / Published: 3 January 2017
View Full-Text   |   Download PDF [1122 KB, uploaded 3 January 2017]   |  

Abstract

CPT (carnitine palmitoyltransferase) II muscle deficiency is the most common form of muscle fatty acid metabolism disorders. In contrast to carnitine deficiency, it is clinically characterized by attacks of myalgia and rhabdomyolysis without persistent muscle weakness and lipid accumulation in muscle fibers. The biochemical consequences of the disease-causing mutations are still discussed controversially. CPT activity in muscles of patients with CPT II deficiency ranged from not detectable to reduced to normal. Based on the observation that in patients, total CPT is completely inhibited by malony-CoA, a deficiency of malonyl-CoA-insensitive CPT II has been suggested. In contrast, it has also been shown that in muscle CPT II deficiency, CPT II protein is present in normal concentrations with normal enzymatic activity. However, CPT II in patients is abnormally sensitive to inhibition by malonyl-CoA, Triton X-100 and fatty acid metabolites. A recent study on human recombinant CPT II enzymes (His6-N-hCPT2 and His6-N-hCPT2/S113L) revealed that the wild-type and the S113L variants showed the same enzymatic activity. However, the mutated enzyme showed an abnormal thermal destabilization at 40 and 45 °C and an abnormal sensitivity to inhibition by malony-CoA. The thermolability of the mutant enzyme might explain why symptoms in muscle CPT II deficiency mainly occur during prolonged exercise, infections and exposure to cold. In addition, the abnormally regulated enzyme might be mostly inhibited when the fatty acid metabolism is stressed. View Full-Text
Keywords: carnitine palmitoyltransferase; myoglobinuria; myopathy; muscle; CPT (carnitine palmitoyltransferase) II deficiency; enzyme activity; enzyme structure carnitine palmitoyltransferase; myoglobinuria; myopathy; muscle; CPT (carnitine palmitoyltransferase) II deficiency; enzyme activity; enzyme structure
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Lehmann, D.; Motlagh, L.; Robaa, D.; Zierz, S. Muscle Carnitine Palmitoyltransferase II Deficiency: A Review of Enzymatic Controversy and Clinical Features. Int. J. Mol. Sci. 2017, 18, 82.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top