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Ceramide Synthase

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Sphingolipid Biology

Summary

Ceramide is an important intracellular second messenger, and a key metabolite in the pathway of sphingolipid biosynthesis where it is formed by N-acylation of sphinganine. In this review, we describe the identification and characterization of a gene family consisting of six genes, the LASS genes, that regulate de novo ceramide synthesis in mammalian cells. Unexpectedly, each LASS homolog tested to date synthesizes ceramide with a specific fatty acid composition. We recently purified LASS5 to homogeneity and demonstrated that it is a bona fide ceramide synthase, displaying the same fatty acid specificity as the membrane-bound enzyme. Moreover, unlike in yeast where an additional subunit, Lipl, is required for ceramide synthase activity, LASS5 does not require any additional subunits, consistent with database analyses showing that mammalian cells do not contain Lipl homologs. The reasons that mammalian cells contain six LASS genes are not known, but presumably each gene is involved in the synthesis of ceramides containing specific fatty acids for use in the regulation of different biological processes.

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© 2006 Springer-Verlag Tokyo

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Pankova-Kholmyansky, I., Futerman, A.H. (2006). Ceramide Synthase. In: Hirabayashi, Y., Igarashi, Y., Merrill, A.H. (eds) Sphingolipid Biology. Springer, Tokyo. https://doi.org/10.1007/4-431-34200-1_3

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