Stereo-specific glycomic codes of the normal and metastatic cancer cell surfaces: Biosynthetic pathways of glycosphingolipids and its probable biological functions

The term "Glycome" is relatively new in the field of Glycobiology. Unlike "Genomic codes" the "glycomic codes" exist on nuclear as well as on the cell surfaces. On the cell surface, the glycomic code resides in the stereo specificity of 10 to 15 different hexoses and pentoses. In this article we provided the stereo specificities of an acceptor mono-or oligosaccharide that determines the in vivo direction of the pathway (or steps) for the formation of intermediate glycosphingolipids (GSLs) of different families, which reside on the cell surfaces. Expressions of these GSLs vary during embryonic development and disease stages. Overall functions of the cell surface glycosphingolipids are unknown. However, unlimited publications over a century have established that these "Glycomes" are involved in a number of intracellular interactions such as cell to matrix, cell to extracellular agents (bacteria, viruses, hormones, toxins, polypeptides, polysaccharides (poly glycomes), polynucleotides, small molecular drugs, or apoptotic agent). In each case interaction between the incoming "glycome" monosaccharide on the molecule attached to the extrinsic molecule and existing oligosaccharides on the cell surfaces is very stereo-specific. These stereo-specific glycosphingolipids are biosynthesized in the Golgi-bodies in a stereo-specific manner during embryonic development (controlled by genomic expression). By comparing Vmax values of stereospecific glycome oligosaccharides (glycosphingolipids) with the same enzyme preparation, we proposed the probable pathways of biosynthesis of the three families of GSLs (Ganglio-, Globo-, and Lacto-GSLs) in any species, at any developmental stage or in the metastatic stage of cancer cells. Existence of specific-sequences of glycolipid families (Ganglio-, Globo-, and Lactofamilies) on the normal or cancer cells is best example of stereo-specific functions of GSLs in biological processes. In different animal RBCs, the major glycosphingolipids (Ceramide-oligoglycomes) of these three families suggest major differences in the normal blood-flow or metastatic migration of the cancer cells. The chemical interactions between "glycomes attached to ceramide or proteins" v/s another stereo-specific "glycome" or nonglycomic molecule was first indicated by comparing Vmax/Km of different similar glycome substrates. Affinity of these glycomes to the specific glycosyltransferase changes with change in the structure of hydrophobic-moieties attached to the acceptor molecules. This review summarizes studies from our lab and others around the world on the specificities of GLS-GLTs activities in the biosynthesis of three families of glycosphingolipids (ganglio-, globo-, and lacto-) and their probable functions. Interaction of these substrates containing different hydrophobic moieties at the active sites could be further proved by future well designed NMR experiments.