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Biochim Biophys Acta. 1990 May 1;1044(1):1-12.

An update of the enzymology and regulation of sphingomyelin metabolism.

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Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30032.


Sphingomyelin is found in plasma membranes and related organelles (such as endocytic vesicles and lysosomes) of all tissues, as well as in lipoproteins. Abnormalities in sphingomyelin metabolism have been associated with atherosclerosis, cancer and genetically transmitted diseases; however, except for Niemann-Pick disease, little is known about the mechanism for these disorders. Sphingomyelin biosynthesis de novo involves ceramide formation from serine and two mol of fatty acyl-CoA followed by addition of the phosphocholine headgroup. The headgroup appears to come from phosphatidylcholine, but other sources have not been ruled out. Factors that influence the rate of sphingomyelin synthesis include the availability of serine and palmitic acid, plus the relative activities of key enzymes of this pathway. Sphingomyelin turnover involves removal of the headgroup and amide-linked fatty acid by sphingomyelinases and ceramidases, respectively, which have been found in both lysosomes (with acidic pH optima) and plasma membranes (with neutral to alkaline pH optima). The enzymes of sphingomyelin turnover release ceramide and free sphingosine from endogenous substrates, which may have implications for the participation of a sphingomyelin/sphingosine cycle as another 'lipid second messenger' system.

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