Many different theories have been advanced concerning the biological roles of the oligosaccharide units of individual classes of glycoconjugates. Analysis of the evidence indicates that while all of these theories are correct, exceptions to each can also be found. The biological roles of oligosaccharides appear to span the spectrum from those that are trivial, to those that are crucial for the development, growth, function or survival of an organism. Some general principles emerge. First, it is difficult to predict a priori the functions a given oligosaccharide on a given glycoconjugate might be mediating, or their relative importance to the organism. Second, the same oligosaccharide sequence may mediate different functions at different locations within the same organism, or at different times in its ontogeny or life cycle. Third, the more specific and crucial biological roles of oligosaccharides are often mediated by unusual oligosaccharide sequences, unusual presentations of common terminal sequences, or by further modifications of the sugars themselves. However, such oligosaccharide sequences are also more likely to be targets for recognition by pathogenic toxins and microorganisms. As such, they are subject to more intra- and inter-species variation because of ongoing host-pathogen interactions during evolution. In the final analysis, the only common features of the varied functions of oligosaccharides are that they either mediate 'specific recognition' events or that they provide 'modulation' of biological processes. In so doing, they generate much of the functional diversity required for the development and differentiation of complex organisms, and for their interactions with other organisms in the environment.

Biological roles of oligosaccharides: all of the theories are correct

The idea that glycosphingolipids (or, briefly, glycolipids) are ubiquitous components of plasma membrane and display cell type-specific patterns perhaps stemmed from the classical studies on glycolipids of erythrocyte membranes.(1,2) Subsequently, plasma membranes of various animal cells were successfully isolated and analyzed; all were characterized by their much higher content of glycolipid than was found in intracellular membranes.(3–8) It is generally assumed that glycolipids are present at the outer leaflet of the plasma membrane bilayer, although this assumption is based only on experiments with surface-labeling by galactose oxidase-NaB[3H]4 of intact and lysed erythrocyte membranes and inside-out vesicles.(9,10) Obviously, further extensive studies of the organization of glycolipid in other eukaryotic cell membranes are necessary. Interestingly, the majority of neutral glycolipids present in plasma membranes are cryptic (see Section 4.2.1).

Glycosphingolipids in Cellular Interaction, Differentiation, and Oncogenesis

The cell wall envelope of gram-positive bacteria is a macromolecular, exoskeletal organelle that is assembled and turned over at designated sites. The cell wall also functions as a surface organelle that allows gram-positive pathogens to interact with their environment, in particular the tissues of the infected host. All of these functions require that surface proteins and enzymes be properly targeted to the cell wall envelope. Two basic mechanisms, cell wall sorting and targeting, have been identified. Cell well sorting is the covalent attachment of surface proteins to the peptidoglycan via a C-terminal sorting signal that contains a consensus LPXTG sequence. More than 100 proteins that possess cell wall-sorting signals, including the M proteins of Streptococcus pyogenes, protein A of Staphylococcus aureus, and several internalins of Listeria monocytogenes, have been identified. Cell wall targeting involves the noncovalent attachment of proteins to the cell surface via specialized binding domains. Several of these wall-binding domains appear to interact with secondary wall polymers that are associated with the peptidoglycan, for example teichoic acids and polysaccharides. Proteins that are targeted to the cell surface include muralytic enzymes such as autolysins, lysostaphin, and phage lytic enzymes. Other examples for targeted proteins are the surface S-layer proteins of bacilli and clostridia, as well as virulence factors required for the pathogenesis of L. monocytogenes (internalin B) and Streptococcus pneumoniae (PspA) infections. In this review we describe the mechanisms for both sorting and targeting of proteins to the envelope of gram-positive bacteria and review the functions of known surface proteins.

Surface Proteins of Gram-Positive Bacteria and Mechanisms of Their Targeting to the Cell Wall Envelope

Background Fabry's disease, lysosomal α-galactosidase A deficiency, results from the progressive accumulation of globotriaosylceramide and related glycosphingolipids. Affected patients have microvascular disease of the kidneys, heart, and brain. Methods We evaluated the safety and effectiveness of recombinant α-galactosidase A in a multicenter, randomized, placebo-controlled, double-blind study of 58 patients who were treated every 2 weeks for 20 weeks. Thereafter, all patients received recombinant α-galactosidase A in an open-label extension study. The primary efficacy end point was the percentage of patients in whom renal microvascular endothelial deposits of globotriaosylceramide were cleared (reduced to normal or near-normal levels). We also evaluated the histologic clearance of microvascular endothelial deposits of globotriaosylceramide in the endomyocardium and skin, as well as changes in the level of pain and the quality of life. Results In the double-blind study, 20 of the 29 patients in the recom...

/pdf/safety-and-efficacy-of-recombinant-human-alpha-galactosidase-40e4hhrkns.pdf

Safety and efficacy of recombinant human alpha-galactosidase A replacement therapy in Fabry's disease.

Quaternary ammonium and tertiary sulfonium compounds in higher plants

[10] Gas-liquid chromatography of carbohydrates

The peptidoglycani of bacterial cell walls is synthesized in a reaction mechanism in which a membrane-bound lipid serves as a carrier for the sugars and amino acids that eventually become part of the peptidoglycan.1 One intermediate in the reaction cycle is represented as lipid-P-P-disaccharide-pentapeptide. This intermediate is common to a number of different bacteria. However, its disaccharidepentapeptide moiety (GlcNAc-M\/urNAc-L-ala-D-glu-L-lys-D-ala-D-ala)2 becomes modified in various ways in different organisms.3 The modified disaccharidepeptide moiety is then transferred to an endogenous acceptor with introduction of a new unit into a growing peptidoglycan. The purpose of the present paper is to report that lipid-P-P-disaccharide-pentapeptide has been obtained in a highly purified form from Mlicrococcus lysodeikticus, and that the nature of the lipid moiety of this intermediate has beeln elucidated. Soon after the discovery of the occurrence of a lipid intermediate in peptidoglyean synthesis, a lipid carrier in the biosynthesis of the lipopolysaccharide of the cell wall of Salmonella was described.4' The structure of this substance is reported in a paper by Wright et al.6 Isolation of Lipid-P-P-Disaccharide-Pentapeptide fromn M. iysodeikticus. Largescale preparation of the lipid intermediate was carried out using techniques essentially the same as those described previously.7 Particulate enzyme was prepared after lysozyme lysis of cells of 111. lysodeilticus8 and incubated with the uridine nucleotide substrates to generate the lipid intermediate. The incubation mixture contained 1000 ml of particulate enzyme prepared in 0.05 111 Tris-HCl buffer, pH 7.4, and 0.01 M M\4gCl2, 1.7 ml of 12 mM\4 UDP-1\'furNAc-pentapeptide (containing 8.7 X 106 cpm of C'4-lysine),9 8 ml of 10 mM\4 UDP-GlcNAc and 30 ml of 5 per cent deoxycholate. Enzyme prepared after lysozyme lysis of cells of M. lysodeikticus is able to synthesize the lipid intermediates, but is unable to utilize these intermediates for peptidoglyean synthesis. Deoxycholate was included in the incubation mixture in order to minimize the addition of endogenous glycine to the lipid intermediate.8 After incubation at 20? for 30 minutes, the mixture was extracted with 1 liter of nbutanol:6 M pyridinium acetate (2:1), pH 4.2, followed by two extractions with the same volume of n-butanol. The combined extracts were back-washed with 2 liters of water and then taken to dryness and redissolved in 50 ml of chloroform: methanol (1: 1). The yield was 3 X 106 cpm (34%, based on UDP-M\'SurNAc-C14pentapeptide). The extract was placed on a column of O-(diethylaminoethyl) cellulose (DEAEcellulose) (2.5 X 25 cm) and eluted as previously described.7 The radioactive eluate obtained with methanol:6 M pyridinium acetate, pH 4.2 (1:1), was pooled

https://www.pnas.org/content/pnas/57/6/1878.full.pdf

Structure of a lipid intermediate in cell wall peptidoglycan synthesis: a derivative of a C55 isoprenoid alcohol.

Alfalfa meal and chloroform extracts of the meal have increased the growth and yield of several plant species. A crystalline substance isolated from the active fraction of alfalfa meal increased the dry weight and water uptake of rice seedlings when sprayed on the foliage or applied in nutrient culture. The substance was identified as triacontanol by mass spectrometry. Sprays containing this compound also increased the growth of corn, and barley grown in soil. Authentic triacontanol produced a similar response over a wide range of concentrations on rice grown in nutrient cultures and tomatoes grown in soil.

https://science.sciencemag.org/content/sci/195/4284/1339.full.pdf

Triacontanol: A New Naturally Occurring Plant Growth Regulator

Structural characterization of oligosaccharides by high-performance liquid chromatography, fast-atom bombardment-mass spectrometry, and exoglycosidase digestion☆

Previous studies from this laboratory have shown that crude, cell-free extracts of Micrococcus lysodeikticus catalyze the incorporation of mannose from GDPmannose into three lipids1 and a mannan.2 Two of the lipids have been identified as a-D-mannosyl-(1 - 3')-diglyceride and a-D-mannosyl-(l - 3)-a-D-mannosyl(1 - 3')-diglyceride.1 In this communication, the results of studies on the structure of the third mannose-containing lipid are presented. All the available evidence indicates that the structure of this compound is mannosyl-l-phosphoryl

Charles C. Sweeley

Papers

[10] Gas-liquid chromatography of carbohydrates

Structure of a lipid intermediate in cell wall peptidoglycan synthesis: a derivative of a C55 isoprenoid alcohol.

Triacontanol: A New Naturally Occurring Plant Growth Regulator

Structural characterization of oligosaccharides by high-performance liquid chromatography, fast-atom bombardment-mass spectrometry, and exoglycosidase digestion☆

The biosynthesis of mannosyl-1-phosphoryl-polyisoprenol in Micrococcus lysodeikticus and its role in mannan synthesis.