Casals, Núria, Zammit, Victor A., Herrero, Laura, Fadó, Rut, Rodríguez-Rodríguez, Rosalía and Serra, Dolors (2016) Carnitine palmitoyltransferase 1C : from cognition to cancer. Progress in Lipid Research, 61 . pp. 134-148. doi:10.1016/j.plipres.2015.11.004 ISSN 0163-7827.

Preview

PDF WRAP_9577424-ms-050116-casals_zammit_et_al_2016_prog_lipid_res.pdf - Accepted Version - Requires a PDF viewer. Download (1947Kb) | Preview

Request Changes to record.

Abstract

Carnitine palmitoyltransferase 1 (CPT1) C was the last member of the CPT1 family of genes to be discovered. CPT1A and CPT1B were identified as the gate-keeper enzymes for the entry of long-chain fatty acids (as carnitine esters) into mitochondria and their further oxidation, and they show differences in their kinetics and tissue expression. Although CPT1C exhibits high sequence similarity to CPT1A and CPT1B, it is specifically expressed in neurons (a cell-type that does not use fatty acids as fuel to any major extent), it is localized in the endoplasmic reticulum of cells, and it has minimal CPT1 catalytic activity with l-carnitine and acyl-CoA esters. The lack of an easily measurable biological activity has hampered attempts to elucidate the cellular and physiological role of CPT1C but has not diminished the interest of the biomedical research community in this CPT1 isoform. The observations that CPT1C binds malonyl-CoA and long-chain acyl-CoA suggest that it is a sensor of lipid metabolism in neurons, where it appears to impact ceramide and triacylglycerol (TAG) metabolism. CPT1C global knock-out mice show a wide range of brain disorders, including impaired cognition and spatial learning, motor deficits, and a deregulation in food intake and energy homeostasis. The first disease-causing CPT1C mutation was recently described in humans, with Cpt1c being identified as the gene causing hereditary spastic paraplegia. The putative role of CPT1C in the regulation of complex-lipid metabolism is supported by the observation that it is highly expressed in certain virulent tumor cells, conferring them resistance to glucose- and oxygen-deprivation. Therefore, CPT1C may be a promising target in the treatment of cancer. Here we review the molecular, biochemical, and structural properties of CPT1C and discuss its potential roles in brain function, and cancer.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Cancer -- Treatment, Carnitine, Lipids -- Metabolism, Homeostasis
Journal or Publication Title:	Progress in Lipid Research
Publisher:	Pergamon Press
ISSN:	0163-7827
Official Date:	January 2016
Dates:	Date Event January 2016 Published 18 December 2015 Available 23 November 2015 Accepted 29 July 2015 Submitted
Volume:	61
Page Range:	pp. 134-148
DOI:	10.1016/j.plipres.2015.11.004
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Date of first compliant deposit:	14 January 2016
Date of first compliant Open Access:	18 December 2016

Request changes or add full text files to a record

Repository staff actions (login required)

View Item

Downloads