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Review

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
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Christo Z. Christov
Int. J. Mol. Sci. 2017, 18(1), 82; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18010082
Received: 31 October 2016 / Revised: 20 December 2016 / Accepted: 28 December 2016 / Published: 3 January 2017
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
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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. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18010082

AMA Style

Lehmann D, Motlagh L, Robaa D, Zierz S. Muscle Carnitine Palmitoyltransferase II Deficiency: A Review of Enzymatic Controversy and Clinical Features. International Journal of Molecular Sciences. 2017; 18(1):82. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18010082

Chicago/Turabian Style

Lehmann, Diana, Leila Motlagh, Dina Robaa, and Stephan Zierz. 2017. "Muscle Carnitine Palmitoyltransferase II Deficiency: A Review of Enzymatic Controversy and Clinical Features" International Journal of Molecular Sciences 18, no. 1: 82. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18010082

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