Simple and complex carbohydrates (glycans) have long been known to play major metabolic, structural and physical roles in biological systems. Targeted microbial binding to host glycans has also been studied for decades. But such biological roles can only explain some of the remarkable complexity and organismal diversity of glycans in nature. Reviewing the subject about two decades ago, one could find very few clear-cut instances of glycan-recognition-specific biological roles of glycans that were of intrinsic value to the organism expressing them. In striking contrast there is now a profusion of examples, such that this updated review cannot be comprehensive. Instead, a historical overview is presented, broad principles outlined and a few examples cited, representing diverse types of roles, mediated by various glycan classes, in different evolutionary lineages. What remains unchanged is the fact that while all theories regarding biological roles of glycans are supported by compelling evidence, exceptions to each can be found. In retrospect, this is not surprising. Complex and diverse glycans appear to be ubiquitous to all cells in nature, and essential to all life forms. Thus, >3 billion years of evolution consistently generated organisms that use these molecules for many key biological roles, even while sometimes coopting them for minor functions. In this respect, glycans are no different from other major macromolecular building blocks of life (nucleic acids, proteins and lipids), simply more rapidly evolving and complex. It is time for the diverse functional roles of glycans to be fully incorporated into the mainstream of biological sciences.

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Biological Roles of Glycans

Chemical Diversity in the Sialic Acids and Related α-Keto Acids: An Evolutionary Perspective

Capsules are protective structures on the surfaces of many bacteria. The remarkable structural diversity in capsular polysaccharides is illustrated by almost 80 capsular serotypes in Escherichia coli. Despite this variation, the range of strategies used for capsule biosynthesis and assembly is limited, and E. coli isolates provide critical prototypes for other bacterial species. Related pathways are also used for synthesis and export of other bacterial glycoconjugates and some enzymes/processes have counterparts in eukaryotes. In gram-negative bacteria, it is proposed that biosynthesis and translocation of capsular polysaccharides to the cell surface are temporally and spatially coupled by multiprotein complexes that span the cell envelope. These systems have an impact on both a general understanding of membrane trafficking in bacteria and on bacterial pathogenesis.

Biosynthesis and Assembly of Capsular Polysaccharides in Escherichia coli

Historical background It is now more than 50 years since N-acetyl-neuraminic acid was first discovered and subsequently characterized by several groups (reviewed in Roseman, 1970; Gottschalk, 1972; Rosenberg and Schengrund, 1976; Schauer, 1982; Faillard, 1989). Relatively soon after its discovery, it became apparent that this molecule was actually the major member of a family of compounds related to neuraminic acid that were christened the 'sialic acids' (Blix etai, 1957). Early studies paid close attention to the different types of sialic acids and the interrelationships between them. However, interest in these complexities subsequently waned and unpublished 'folk-lore' had it that modified sialic acids were species-specific curiosities found only in a few tissues, such as erythrocytes and submaxillary glands. In fact, many investigators in the 1970s and 80s used the terms W-acetyl-neuraminic acid' and 'sialic acid' synonymously. Thus, for example, when structural or biological changes were noted following treatments with a sialidase (neuraminidase), it was often assumed that the sialic acid released was A^-acetyl-neuraminic acid. It is now clear tjiat the different types of sialic acids are much more widely distributed than previously thought. This review attempts to briefly summarize current knowledge concerning the occurrence, structure, biochemistry and biological significance of this diversity in the sialic acids. Particular attention is given to the two most common and better studied modifications: the addition of 0-acetyl esters to the hydroxyl groups at the 4-, 7-, 8- and 9-positions, and the conversion of the 7V-acetyl group to an /V-glycolyl group. Given the breadth of the review, the bibliography is only representative, and tends to emphasize more recent studies.

/pdf/diversity-in-the-sialic-acids-2cnnxmsk42.pdf

Diversity in the sialic acids

Every cell in nature carries a rich surface coat of glycans, its glycocalyx, which constitutes the cell's interface with its environment. In eukaryotes, the glycocalyx is composed of glycolipids, glycoproteins, and proteoglycans, the compositions of which vary among different tissues and cell types. Many of the linear and branched glycans on cell surface glycoproteins and glycolipids of vertebrates are terminated with sialic acids, nine-carbon sugars with a carboxylic acid, a glycerol side-chain, and an N-acyl group that, along with their display at the outmost end of cell surface glycans, provide for varied molecular interactions. Among their functions, sialic acids regulate cell-cell interactions, modulate the activities of their glycoprotein and glycolipid scaffolds as well as other cell surface molecules, and are receptors for pathogens and toxins. In the brain, two families of sialoglycans are of particular interest: gangliosides and polysialic acid. Gangliosides, sialylated glycosphingolipids, are the most abundant sialoglycans of nerve cells. Mouse genetic studies and human disorders of ganglioside metabolism implicate gangliosides in axon-myelin interactions, axon stability, axon regeneration, and the modulation of nerve cell excitability. Polysialic acid is a unique homopolymer that reaches >90 sialic acid residues attached to select glycoproteins, especially the neural cell adhesion molecule in the brain. Molecular, cellular, and genetic studies implicate polysialic acid in the control of cell-cell and cell-matrix interactions, intermolecular interactions at cell surfaces, and interactions with other molecules in the cellular environment. Polysialic acid is essential for appropriate brain development, and polymorphisms in the human genes responsible for polysialic acid biosynthesis are associated with psychiatric disorders including schizophrenia, autism, and bipolar disorder. Polysialic acid also appears to play a role in adult brain plasticity, including regeneration. Together, vertebrate brain sialoglycans are key regulatory components that contribute to proper development, maintenance, and health of the nervous system.

https://www.physiology.org/doi/pdf/10.1152/physrev.00033.2013

Sialic Acids in the Brain: Gangliosides and Polysialic Acid in Nervous System Development, Stability, Disease, and Regeneration

O-acetylation and de-O-acetylation of sialic acids. 7- and 9-o-acetylation of alpha 2,6-linked sialic acids on endogenous N-linked glycans in rat liver Golgi vesicles.

Intramolecular self-cleavage of polysialic acid.

Acetyl-coenzyme A:polysialic acid O-acetyltransferase from K1-positive Escherichia coli. The enzyme responsible for the O-acetyl plus phenotype and for O-acetyl form variation.

O-acetylation and de-O-acetylation of sialic acids. Purification, characterization, and properties of a glycosylated rat liver esterase specific for 9-O-acetylated sialic acids.

H H Higa

Papers

O-acetylation and de-O-acetylation of sialic acids. 7- and 9-o-acetylation of alpha 2,6-linked sialic acids on endogenous N-linked glycans in rat liver Golgi vesicles.

Intramolecular self-cleavage of polysialic acid.

Acetyl-coenzyme A:polysialic acid O-acetyltransferase from K1-positive Escherichia coli. The enzyme responsible for the O-acetyl plus phenotype and for O-acetyl form variation.

O-acetylation and de-O-acetylation of sialic acids. Purification, characterization, and properties of a glycosylated rat liver esterase specific for 9-O-acetylated sialic acids.

Structural, immunological, and biosynthetic studies of a sialic acid-specific O-acetylesterase from rat liver.