Lectins are one of the most important physiologically active ingredients and potent exogeneous biological signals in the diet. Although the amounts of lectins in foodstuffs can vary considerably, they can dramatically affect the entire digestive tract and its bacterial population, body metabolism and health. Their extraordinary effectiveness stems from resistance to gut proteolysis and a high and specific chemical reactivity with endogenous surface receptors of the epithelial cells of the gut of both higher animals and lower organisms. Lectins are powerful oral and parenteral immunogens and some of their physiological effects are intricately linked to interference with immune function. However, the primary effects and the potency of lectins as biological signals are the direct result of their specific chemical reactivity with saccharides. As these reactions are predictable, the use of lectins as blockers of pathogens, immune stimulants, hormone modulators and metabolic agents in clinical-medical applications and as natural insecticides in transgenic plants, offers great promise.

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Hepatocyte growth factor (HGF), also referred to as scatter factor (SF), is an important paracrine mediator of epithelial-mesenchymal cell interactions. It is secreted by mesenchymal cells and affects epithelial cell proliferation, motility and morphology. These diverse biological activities are a result of HGF/SF binding to and activating its high affinity (K_d=0.1-0.5nM) tyrosine kinase receptor called c-Met. The c-Met receptor is expressed in many epithelial and endothelial cell types but not in mesenchymal cells. In addition to c-Met, HGF/SF also binds heparin and heparan sulfate proteoglycans on cell surfaces, albeit with a 10-fold lower affinity (K_d=1-5nM). Both size and charge of heparan sulfate-derived oligosaccharides determine binding affinity to HGF. Furthermore, those binding determinants for HGF differ from those of FGF. Coincubation of soluble heparin and other heparin-like molecules with HGF/SF results in oligomerization of the growth factor and potentiation of its mitogenic activity in cell culture. Recent data indicate that the mitogenic response of cells to HGF/SF and its truncated variants called NK1 and NK2, may be determined by heparan sulfate proteoglygans expressed on the cell surface. Based on these data we propose a model, similar to that of fibroblast growth factor, where soluble heparinlike molecules (or cell surface heparan sulfate proteoglycans) can stabilize HGF/SF oligomers thus facilitating c-Met receptor-dimerization and cellular signaling.

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It generally is agreed that initiation of a glycogen molecule occurs through the addition of a linear array of glucose molecules to a protein referred to as glycogenin. The addition of glucosyl units is catalyzed by glycogenin itself. The product is then branched and expanded by other enzymes. This process has been studied best in skeletal muscle. In skeletal muscle, all of the glycogenin is incorporated into glycogen molecules (1) The glycogen molecules also are all presumed to be proteoglycans.
In liver, glycogenin is free, i.e., not incorporated into a proteoglycogen molecule in the fasted state and it becomes incorporated into a glycogen molecule only later in the feeding phase. Furthermore, preliminary data suggest that most of the glycogen molecules are not proteoglycans but rather are independent of glycogenin. Thus, the character and biosynthesis of glycogen in liver appears to be much more complex than in skeletal muscle. Regulation of the various forms of glycogen also is likely to be complex.

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Sialylated oligosaccharides of glycoproteins and glycolipids have been implicated in many biological processes such as cell adhesion and receptor recognition. The structural diversity and regulated expression of sialylglycoconjugates appear to correlate with their functions. Sialyltransferase genes will be very useful for elucidating the biological functions of sialylglycoconjugates and for understanding the mechanisms of their regulated expression. To date, 12 kinds of sialyltransferase genes have been cloned. The enzymatic analyses have revealed that one linkage can be synthesized by multiple enzymes. Each of the sialyltransferase genes was expressed differentially in tissue-, cell-type-, and stage-specific manner, to regulate the sialylation pattern on the cell surface at the transcriptional level. The biological functions of the specific sialylglycoconjugates have been demonstrated directly by using the cloned sialyltransferase cDNAs. In addition, isolation of the sialyltransferase cDNAs enabled us to synthesize large amounts of sialylated oligosaccharides or to manipulate the carbohydrate structure of recombinant therapeutic glycoproteins. An understanding of the functional significance of sialylglycoconjugates will lead to a variety of applications including the invention of new therapeutic drugs.

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