Sphingomyelin-ceramide pathway

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P., 1996, Opposite effects of tumor necrosis factor a on the sphingomyelin-ceramide pathway in two myeloid leukemia cell lines Role of transverse sphingomyelin distribution in the plasma membrane. Blood 88 1465-1472. 

Cai, Z., Bettaieb, A., Mahdani, N. E., Legres, L. G., Stancou, R., Masliah, J., and Chouaib, S. (1997). Alteration of the sphingomyelin/ceramide pathway is associated with resistance of human breast carcinoma MCF7 cells to tumor necrosis factor-alpha-mediated cytotoxicity. J Biol Chem 111, 6918-6926. 

Lozanski, G., Berthier, F., and Kushner, I. The sphingomyelin-ceramide pathway participates in cytokine regulation of C-reactive protein and serum amyloid A, but not alpha-fibrinogen. Biochem J 328 (Pt 1) (1997) 271-275. 

Fig. 6.12. Formation and function of the messenger substance ceramide. The starting point for the synthesis of ceramide is sphingomyelin, which is converted to phosphocholine and ceramide by the action of a sphingomyelinase. Sphingomyelinase is activated via a pathway starting from tumor necrosis factor a (TNFa) and its receptor. Ceramide serves as an activator of protein kinases and protein phosphatases. RI fatty add side chain.

FIGURE 1 Pathways for the breakdown of GM1, globoside, and sphingomyelin to ceramide. A defect in the enzyme hydrolyzing a particular step is indicated by and the disease that results from accumulation of the partial breakdown product is noted. 

The pathways to sphingomyelin and glycosphingolipids. Figure 19.13 elaborates on some pathways from ceramide to glycosphingolipids. 

Acid sphingomyelinase is a lysosomal enzyme that catalyzes the breakdown of sphingomyelin to ceramide and phosphoryl-choline.A deficiency of this enzyme leads to lysosomal accumulation of sphingomyelin in patients with Niemann-Pick disease. Recent data indicate that correct intracellular targeting of acid sphingomyelinase to lysosomes is dependent on the mannose 6-phosphate-mediated pathway. Does this imply that the I-cell patient will present with Niemann-Pick symptoms Can I-cell disease be viewed as a constellation of many lysosomal storage diseases ... 

In the pathway that produces sphingomyelin from ceramide, what compound is converted to 1,2-diacylglycerol in the process ... 

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