Glycosphingolipids synthesis

Sulfation of the carbohydrate chain occurs after the monosaccharide to be sulfated has been incorporated into the growing carbohydrate j chain. The source of the sulfate is 3 -phosphoadenosyl-5 -phospho-sulfate (PAPS, a molecule of AMP with a sulfate group attached to the 5-phosphate). Sulfotransferases cause the sulfation of the carbohydrate chain at specific sites. [Note An example of the synthesis of a sulfated glycosaminoglycan, chondroitin sulfate, is shown in Figure 14.11.] PAPS is also the sulfur donor in glycosphingolipid synthesis. [Note A defect in the sulfation process results in one of several autosomal recessive disorders that affect the proper development and maintenance of the skeletal system. This illustrates Ihe importance of the sulfation step.]... 

Sphingomyelin Is Formed Directly from Ceramide Glycosphingolipid Synthesis Also Starts from Ceramide... 

Glycosphingolipid Synthesis Also Starts from Ceramide... 

Shapiro and co-workers have described [89] (in a paper submitted just before the death of this pioneer in the field of glycosphingolipid synthesis — for a review of his extensive work in this area see Ref. [1]) a synthesis of the thio-analogue (88) of glucosyl ceramide (and the saturated derivative) from 2,3,4,6-tetra-0-acetyl-l-mercapto- 3-D-glucopyranose (86) and the 1-deoxy-l-iodoceramide derivative (85) in the presence of l,8-diazabicyclo[5.4.0]undec-7-ene. The product (87) was deacylated with methano-lic barium methoxide to give (88). 

JU. Cloning of Gbs synthase, the key enzyme in globo-series 55. glycosphingolipid synthesis, predicts a family of 1,4 glycosyn-transferases conserved in plants, insects and mammals. J. Biol. 56. Chem. 2000 275 25315-25321. 

Yamashita T, Wada R, Sasaki T, Deng C, Bierfreund U, Sandhoff K, Proia RL. A vital role for glycosphingolipid synthesis during development and differentiation. Proc. Natl. Acad. Sci. U.S.A. 1999 96 9142-9147. 

Ichikawa S, Sakiyama H, Suzuki G, Hidari KI, Hirabayashi Y (1996) Expression cloning of a cDNA for human ceramide glucosyltransferase that catalyzes the first glycosylation step of glycosphingolipid synthesis. Proc Natl Acad Sci USA 93 4638 643... 

Zhao, H., Przybylska, M., Wu, I.H., Zhang, J., Siegel, C., Komarnitsky, S., Yew, N.S. and Cheng, S.H., Inhibiting glycosphingolipid synthesis improves glycemic control and insulin sensitivity in animal models of type 2 diabetes, Diabetes 56 (2007) 1210-1218. 

Glycosphingolipid Synthesis Group, Laboratory for Immune Regulation, Research Center for Allergy and Immunology (RCAI), RIKEN, Wako-shi, Saitama, Japan... 

We thank Prof. Masaru Taniguchi (RIKEN, RCAI) for his guidance and generous support throughout our NKT cell study and glycosphingolipid synthesis. We also thank Prof Ken-ichiro Seino (Hokkaido University), Dr Hiroshi Watarai (The Institute of Medical Science,... 

Designer en2ymes for glycosphingolipid synthesis by directed evolution... 

Felding-Habermann,B., Igarashi,Y, Fenderson, B.A., Park, L.S., Radin, N.S., Inokuchi, J., Strassmann, G., Handa, K., and Hakomori, S., 1990, A ceramide analogue inhibits T cell proliferative response through inhibition of glycosphingolipid synthesis and enhancement of N,N-dimethylsphingosine synthesis. Biochemistry. 29(26) 6314-6322. 

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