Sphingolipid metabolism in metazoan cells consists of a complex interconnected web of numerous enzymes, metabolites and modes of regulation. At the centre of sphingolipid metabolism reside CerSs (ceramide synthases), a group of enzymes that catalyse the formation of ceramides from sphingoid base and acyl-CoA substrates. From a metabolic perspective, these enzymes occupy a unique niche in that they simultaneously regulate de novo sphingolipid synthesis and the recycling of free sphingosine produced from the degradation of pre-formed sphingolipids (salvage pathway). Six mammalian CerSs (CerS1–CerS6) have been identified. Unique characteristics have been described for each of these enzymes, but perhaps the most notable is the ability of individual CerS isoforms to produce ceramides with characteristic acyl-chain distributions. Through this control of acyl-chain length and perhaps in a compartment-specific manner, CerSs appear to regulate multiple aspects of sphingolipid-mediated cell and organismal biology. In the present review, we discuss the function of CerSs as critical regulators of sphingolipid metabolism, highlight their unique characteristics and explore the emerging roles of CerSs in regulating programmed cell death, cancer and many other aspects of biology.
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February 2012
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Review Article|
January 16 2012
Ceramide synthases at the centre of sphingolipid metabolism and biology
Thomas D. Mullen;
Thomas D. Mullen
*Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, U.S.A.
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Yusuf A. Hannun;
Yusuf A. Hannun
1
†Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425
1Correspondence may be addressed to either of these authors (email [email protected] or [email protected]).
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Lina M. Obeid
Lina M. Obeid
1
*Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, U.S.A.
†Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425
‡Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29401, U.S.A.
1Correspondence may be addressed to either of these authors (email [email protected] or [email protected]).
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Publisher: Portland Press Ltd
Received:
September 09 2011
Revision Received:
October 12 2011
Accepted:
October 27 2011
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem J (2012) 441 (3): 789–802.
Article history
Received:
September 09 2011
Revision Received:
October 12 2011
Accepted:
October 27 2011
Citation
Thomas D. Mullen, Yusuf A. Hannun, Lina M. Obeid; Ceramide synthases at the centre of sphingolipid metabolism and biology. Biochem J 1 February 2012; 441 (3): 789–802. doi: https://doi.org/10.1042/BJ20111626
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