Ceramide synthase

Bose, R., Verheij, M., Haimovitz-Friedman, A., Scotto, K., Fuks, Z., and Kolesnick, R., 1995, Ceramide synthase mediates daunombicin-induced apoptosis an alternative mechanism for generating death signals. Cell 82 405-414. 

Very recently, two yeast (5. cerevisiae) alkaline ceramidases, phytoceramidase (YPClp) and dihydroceramidase (YDClp), were cloned and partially characterized by Mao et al (2000a, b). YPClp was cloned as a high copy suppressor of the growth inhibition by FBI as it has fumoitisin resistant ceramide synthase activity. The second alkaline ceramidase, YDClp was identified by sequence homology to YPClp. 

YPClp exhibits reverse activity in cells and in vitro. This activity is not inhibited by FBI and is fatty acyl-CoA independent, suggesting that the reverse activity of YPClp is distinct from the FBI inhibitable ceramide synthase activity which uses fatty acyl-CoA as substrate, but not a free fatty... 

It is important to note that these reverse activities of CDases are distinct from the major CoA-dependent ceramide synthase activity that is present in the ER and is thought to be responsible for de novo synthesis of Cer. Further, this reverse activity of CDases, may emerge as a new pathway of Cer formation, different from the known de novo or sphingomyelinases pathways. 

Biochemical characterization of the reverse activity of rat brain ceramidase A CoA-independent and fumonisin B1 insensitive ceramide synthase. J. Biol. Chem. published February 8, 2001 as 10.1074/jbc.M009331200. 

Mao, C., Xu, R., Bielawska, A., and Obeid, L.M., 2000a, Cloning of an alkaline ceramidase from Saccharomyces cerevisiae. An enzyme with reverse (CoA-independent) ceramide synthase achvity. J. Biol. Chem., 275 6876-6884. 

The chemical structure of fumonisin (Fig. 5.IB) is remarkably similar to that of the sphingoid bases sphinganine (Sa) and sphingosine (So), and fumonisin has been shown to inhibit the enzyme ceramide synthase in de novo sphingolipid metabolism (Wang et al., 1991). Ceramide synthase... 

Constable, P. D., Smith, G. W., Rottinghaus, G. E., Tumbleson, M. E., and Haschek, W. M. (2003). Fumonisin-induced blockade of ceramide synthase in sphingolipid biosynthetic pathway alters aortic input impedance spectrum of pigs. Am. J. Phusiol. Heart Circ. Physiol. 284(6), H2034 2044. 

Riley, R. T., Voss, K. A., Norred, W. P., Bacon, C. W., Meredith, F. I., and Sharma, R. P. (1999). Serine palmitoyltransferase inhibition reverses antiproliferative effects of ceramide synthase inhibition in cultured renal cells and suppresses free sphingoid base accumulation in kidney of BALBc mice. Environ. Toxicol. Pharmacol. 7,109-118. 

Riley, R. T., Voss, K. A., Speer, M., Stevens, V. L., and Gelineau-van Waes, J. (2006). Fumonisin inhibition of ceramide synthase A possible risk factor for human neural tube defects. In "Sphingolipid Biology," (Y. Hirabayashi, A. H. Merrill, Jr., and Y. Igarashi, Eds.), pp. 345-362. Springer, Toyko. 

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