Biomolecules serve different functions in a cell. The three major classes of biomolecules in the cell are: proteins, nuclei acids and carbohydrates. These molecular structures serve nearly similar functions in most organisms. Though the function of protein in forming cell architecture, signaling and communication is well known, little is known about the role of carbohydrate in communication. Nevertheless, it goes un-denying that carbohydrates are indispensable for cellular communication and signaling, just like proteins and nucleic acids. The paper titled, Carbohydrates in Cell Recognition, by the authors Nathan Sharon and Halina Lis, is a good review that elucidates the significance of carbohydrates in cell recognition and communication. Carbohydrates based cell communication is important for normal physiology and pathology of cells. The paper present events in cell recognition and communication that involves carbohydrate molecules. (Sharon and Lis 82-89)
Carbohydrates are capable of forming structures that are extraordinarily complex than protein and nuclei acids. Thus, it is difficult to describe its structure like that of proteins and nuclei acid. While nuclei acid and amino acid can form only a limited number of bonds to form polymers like nucleic acid and proteins; carbohydrates can connect in multiple ways. For example, two monosaccharide can bond in different ways, to give rise to 11 different disaccharides each time. Likewise, four different monosaccharide are capable of forming 35,560 unique tetrasaccharides, by different permutations and combinations. The diversity in carbohydrate biomolecule, enables them to communicate different signals with specificity and sensitivity. The ability of carbohydrate to form an O-glycosidic bond with any molecule that has a free OH group and its ability to form N-glycosidic bond with molecules that have an amine group, is responsible for this unique ability of carbohydrate. (Sharon and Lis 82-89)
The ability of antibodies to recognize specific carbohydrate moiety on the cell, was known through the interaction of antibody with carbohydrate, though discovery of ABO blood groups and through discovery of lectins. Now we know that even a mild alteration in the polysaccharide linkage can prevent cell recognition. For example, cell surface glycoprotein is important in cell recognition. Alteration of these surface glycoprotein, by altering the carbohydrate moiety can affect this process. (Sharon and Lis 82-89)
Apart from cell to cell recognition, carbohydrate has also played a role in embryogenesis, cell signaling, immune response, cell adhesion etc. Attachment of bacteria to the host is important for infection to occur. Bacterial lectins attach to cell surface carbohydrate, to gain entry into the body and cause infection. Scientists of Fred Hutchinson Cancer Research Centre have identified that two carbohydrates: SSEA-1 and Lewisx (Lex) that begin to appear on embryonic cells in the 8 to 16 cell stage, help these cells to come together and form a soft compact ball. When these carbohydrate molecules are blocked using certain soluble molecules, the embryonic cells failed to form compact balls. (Sharon and Lis 82-89)
Lectins are proteins and they are not immunological in origin. They have the ability to bind reversibly and specifically to specific carbohydrate moieties. The hemagglutinin produced by certain bacteria and virus, are lectins and they cause hemagglutination. Lectins are found ubiquitously in organism ranging from viruses, bacteria, fungi, plants, animals, insects and even humans. Lectins have carbohydrate binding domain. While some have only one, other may have more than one carbohydrate binding domain. They are very heterogeneous in structure, specific to the carbohydrate they recognize and also vary in their function. Some of the well-known carbohydrate group that bind to lectins include: mannose-mannose, glucose, mannose-maltose, Gal/GalNAc, GlcNAc, Fucose and Sialic acid. Lectins are immunogenic and can trigger immune response when taken orally or parentally. (Sharon 53R-62R)
J. P. Duguid, discovered the bacteria lectin hemagglutinin using two different experiments. In one, he exposed the bacteria to a wide range of substance and found that the Escherichia coli lectin is specific to monosaccharide mannose. He found that only the monosaccharide mannose and very similar sugars could inhibit hemagglutination. He also observed these bacteria under the microscope to discover that the mannose binding hemagglutinin was located on hairy appendages seen on the bacterial surface. (Sharon and Lis 82-89)
Group A Streptococci has lectin called the M-protein that binds specifically to the sialic acid receptors seen in the respiratory tract and urinary tract of the host. Thus, the infection caused by these bacteria is specific to these organs. (Ryan, Pancholi and Fischetti 7402-7412)
The K88 strain E. coli is a common cause of diarrhea and death in piglets, causing loss to farmers who rear pigs. These bacteria specifically adhere to the intestinal epithelium of piglets, but not the epithelium of adult pigs. Gibbon discovered that mutant bacteria, unlike K88 did not bind to the epithelium. Similarly, certain piglets that lacked the carbohydrate moiety that helped the bacteria to attach, were resistant to K88 strain. Scientists discovered that certain mannose containing glycoprotein that were present in the intestine of some susceptible piglets, but absent in the adults, helped in the adherence of P fimbriae protein (lectin) of the K88 strain to the intestine.
Scientist are considering inhibition of bacteria adhesion to host leptin using molecules that resemble host surface carbohydrate. These molecules can compete with host cell carbohydrate and block the carbohydrate binding domain of the bacteria. This will prevent adhesion and infection. (Sharon and Lis 82-89)
Carbohydrate recognition is also important for leukocyte migration. Leukocytes attach to L-selectin on the surface of the endothelium, before migrating out of the blood vessels. L-selectin also guides leukocyte migration to the peripheral lymph node. Inflammatory cytokines and chemokines released during inflammation can increase the expression of L-selectin in the endothelium and enables leukocyte rolling. (Venturi et al. 713-724)
Metastatic tumor cells have high levels of sialic acid expression on their surface. This affects cell to cell interaction property of these cells. Sialoprotein regulates a variety of functions in the cell. To begin with, it regulates the structure of glycoprotein or glycolipid of which it is a component. It also serves other functions like the stability of the cell, trafficking and function. Removal or blocking of sialic acid of the cancerous cell, targeted these cells to programmed cell death. (Bull et al. 3199-3204)
The article, Carbohydrates in Cell Recognition, provided valuable insight into its important in cell structure and function. Though the function of some of the carbohydrate polymers is understood from this article, I would like to know how to map the complete carbohydrate language used by the cell. While genomic deals with all nucleotide information of the cell and Proteomic deals with all protein in a cell, there is no such profiling available for carbohydrates. Considering the complexity of carbohydrate, the task seems challenging.
Work Cited
Bull, C. et al. "Sialic Acids Sweeten A Tumor's Life". Cancer Research 74.12 (2014): 3199-3204. Web. 4 July 2016.
Ryan, P. A., V. Pancholi, and V. A. Fischetti. "Group A Streptococci Bind To Mucin And Human Pharyngeal Cells Through Sialic Acid-Containing Receptors". Infection and Immunity 69.12 (2001): 7402-7412. Web. 4 July 2016.
Sharon, N. "History Of Lectins: From Hemagglutinins To Biological Recognition Molecules". Glycobiology 14.11 (2004): 53R-62R. Web. 4 July 2016.
Sharon, Nathan and Halina Lis. "Carbohydrates in Cell Recognition". Sci Am 268.1 (1993): 82-89. Web. 4 July 2016.
Venturi, Guglielmo M et al. "Leukocyte Migration Is Regulated by L-Selectin Endoproteolytic Release". Immunity 19.5 (2003): 713-724. Web. 4 July 2016.
