Glucosylceramide synthesis

Radin, N. S., Shayman,J. A.,and Inokuchi,J. (1993). Metabolic effects of inhibiting glucosylceramide synthesis with PDMP and other substances. Adv. Lipid Res. 26, 183-213. 

Futerman AH, Pagano RE. Determination of the intracellular sites and topology of glucosylceramide synthesis in rat Uver. Biochem. J. 1991 280 295-302. 

Boldin, S. Futerman, A. H. Glucosylceramide synthesis is required for basic fibroblast growth factor and laminin to stimulate axonal growth. J. Neurochem. 1997, 68, 882-885. 

Schweizer, A., Clausen, H., Van Meer, G., and Hauri, H.-R, 1994, Localization of O-glycan initiation, sphingomyelin synthesis, and glucosylceramide synthesis in Vero cells with respect to the endoplasmic reticulum-Golgi intermediate compartment, J. Biol. Chem. 269 4035-4041. 

Ceramide formed in mammalian systems is metabolized to sphingomyelin, glycosphingolipids, and ceramide 1-phosphate by the actions of sphingomyelin synthase, glucosylceramide synthase, and ceramide kinase on ceramide, respectively. Ceramide synthesized in the endoplasmic reticulum is transported to the Golgi apparatus for synthesis of complex sphingolipids (93). Sphingomyelin is synthesized from ceramide by transfer of the... 

Boucheron C, Desvergnes V, Compain P, Martin OR, Lavi A, Mackeen M, Wormald MR, Dwek RA, Butters TD. Design and synthesis of imino-sugar-based inhibitors of glucosylceramide synthase the search for new therapeutic agents against Gaucher disease. Tetrahedron Asymmetry 2005 16 1747-1756. 

Bodennec J., Pelled D., Riebeling C., Trajkovic S., Futerman A.H., Phosphatidylcholine synthesis is elevated in neuronal models of Gaucher disease due to direct activation of CTP phosphocholine cytidylyltransferase by glucosylceramide, Faseb J 16 (2002) 1814-1816. 

The most common cerebrosides include galactosylceramide, glucosylceramide, and sulfatides (see Figure 19.14 for synthesis scheme). Sulfatides are made by transferring a sulfate group to a galactosylceramide (Figure 19.14). 

Bovine milk contains an enzyme, in soluble form, which catalyses the transfer of D-galactose from UDP-D-galactose to D-glucosylceramide. The synthesis of the product, lactosylceramide, was inhibited by the presence of a-lactalbumin. Lactosylceramide was also an effective acceptor of D-galactose, but neutral glycosphingolipids or gangliosides were very poor receptors. 

Figure 12.15 Formation of the lipid barrier of human skin. The top layer of the epidermis called stratum corneum is a hornified and inert barrier. Its primary functions are regulation of the skin s moisture content and protection of the underlying tissues against external influences. Due to its structure it is often compared to a brick wall in which the non-viable keratin-filled corneocytes are embedded like bricks in a matrix of intercellular lipids. Synthesis of the stratum corneum lipids starts in deeper skin layers, where lipids (mainly glucosylceramides and sphingomyelin) are produced and packaged in so-called lamellar bodies . During differentiation and maturation, these lipids are enzymatically converted to ceramides and finally assembled into densely packed lamellar structures surrounding the corneocytes and filling the intercellular spaces of the stratum corneum.

Wennekes T, van den Berg RJBHN, Bonger KM et al (2010) Synthesis and evaluation of dimeric lipophilic iminosugars as inhibitors of glucosylceramide metabolism. Tetrahedron Asymmetry 20 836-846... 

Increased levels of gangliosides, sulphatides, and neutral glycosylceramides have been found in the skeletal muscles of rabbits with experimental dystrophy when compared to controls. Data obtained from the in vitro synthesis of glycolipids in rabbit platelets have indicated that D-glucose is used mainly for the production of D-glucosylceramide since this glycolipid is common to all... 

Olshefski R, Ladisch S. Synthesis, shedding, and intercellular transfer of human medulloblastoma ganglio-sides abrogation by a new inhibitor of glucosylceramide synthase. / Neurochem. 1998 70(2) 467-472. 

P4-GalT VI has been identified as a lactosylceramide synthase [175]. Whether it acts on substrates other than glucosylceramide has not been determined. Finally, the p4-GalT involved in the first step of the synthesis of the GlcA(pi-3)Gal(pi-3)Gal(pi-4)Xyl core region of proteoglycans has recently been cloned and seems to be another member of this family [176, 195]. It is proposed to refer to this enzyme as p4-GalT VII. 

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