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30322, USA Sphingomyelin synthesis begins with the condensation of serine and palmitoyl-CoA to make 3-ketosphinganine, which is rapidly reduced to sphinganine, and acylated by ceramide synthase to dihydroceramides. Ceramide synthase is inhibited by an important class of mycotoxins (termed fumonisins) that are hepatotoxic, hepatocarcinogenic, and cause several animal diseases (Merrill et al., 1996 Trends Cell Biol. 6, 218). Dihydroceramides are converted to ceramides (N-acylsphingosines) by a desaturase reaction utilizing molecular oxygen and a reduced pyridine nucleotide (Michel, C., van Echten-Deckert, G., Rother, J., Sandhoff, K., Wang, E., Merrill, A.H., submitted for publication), and incorporated into sphingomyelin by the transfer of phosphocholine from phosphatidylcholine (or formation of ceramide-ethanolamine followed by methylation with Sadenosylmethionine). Sphingomyelin synthesized by hepatocytes is incorporated into cellular membranes and secreted as part of very-low-density lipoproteins (VLDL) (J. Biol. Chem. 270, 13834, 1995). A large fraction of the sphingomyelin in hepatocytes is hydrolyzed in response to interleukin-1i (IL-1i) (J. Biol. Chem. 270, 1995, 25233-25238)

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Publisher

Elsevier Science; Elsevier ; Elsevier BV (ISSN 0009-3084)

Published

1997

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)