Glycosidic Bonds, Disaccharides, and Polysaccharides

Nomenclature

(-syl)-(linkage)-(-ose)

Proteoglycans Functions

-Formation of extracellular matrix -Interact with a variety of receptors -Important component of connective tissue and cartilage

Homopolysaccharides Functional Roles

-Fuel storage: Starch and glycogen -Structural: Cellulose and chitin

Why are glycogen and starch so enormous?

-Osmolarity (concenration of glycogen in cell 0.01uM would equal 0.4M as glucose monomers -cause large osmotic imbalance -Provides free-E to draw glucose from extracellular space (about 5mM glucose in blood) -Low effective glucose concentration inside cells creates concentration gradient to draw blood glucose inward

Extracellular Matrix Main Components

-Proteoglycan aggregates -Collagen fibers -Elastin (a fibrous protein)

Glycolipid

A lipid with covalently bound oligosaccharide -outer-leaflet of eukaryotes and bacterial cell membranes -rich in neurons (binding site for lectins and myelin formation) -RBC (determines blood groups)

Abundance

About half of mammalian proteins are glycoproteins -viral proteins are heavily glycosylated, helps evade the immune system -glycoproteins are rare in bacteria

Additional H-bonds between chains

Allow structure to be tough and water-insoluble

Branching

Allows for rapid degradation and synthesis -enzymatic processing occurs at the many non-reducing ends

Glycogen

BRANCHED homopolysaccharide of glucose -functions as the main storage polysaccharide in animals -glucose monomers from alpha 1-->4 linked chains -branched-points with alpha 1-->6 linkers every 8-12 residues -molecular weight reaches several millions

Amylopectin

Branched like glycogen byt the branch-points with alpha 1-->6 linkers occur every 24-30 residues -nonreducing ends and reducing ends

Glycoproteins (glycoconjugates)

Carbohydrate attached via its anomeric carbon -added by glycosyltransferases -removed by glycoside hydrolases

Lectins

Carbohydrate binding proteins that translate the 'sugar code'

Mallard Reaction

Complex reaction between reducing sugar and amino acids -gives brown color to cooked foods and flavor profile

Proteoglycans

Covalently linked to sulfated glucoseaminoglycans (GAGs) (heteropolysaccharide) -40 types both as secreted (extracellular and membrane proteins)

HIV Vaccine Design Strategy

Development of neutralizing antibodies targeted at conserved 'holes' in the glycan shield -conserved holes

Maltose

Disaccharide of two glucose molecules via 1-->4 glycosidic bond -still reducing sugar because the cyclic hemiacetal end is in equilibrium with open chain form

Glycogen and starch

Enormous storage molecules glycogen >1M residues starch >200M residues

Heteropolysaccharides Functional Roles

Extracellular support

Metabolism of Glycogen & Starch

Glycogen and starch often form granules in cells -contain enzymes that synthesize and degrade these polymers

O-linked glycoprotein

Glycosidic bond to hydroxyl of Ser/Thr

Diversity of polysaccharides

Have a variety of functional roles, and come in a diverse variety of structures (more subunits and types of linkages than proteins).

Glycogen and amylopectin

Have one reducing end but many nonreducing ends (due to branching)

Viral Coat Proteins

Heavily glycosylated -provides mechanisms to "shield" and evade immune response (i.e. glycan shield of HIV) -conserved hole

The sugar code

In additional to fuel and structural roles, polysaccharides have important roles as information carries (rich complexity of structure) Examples: Binding sites for extracellular signals i.e. growth factors Cell-to-cell communication i.e. immune response Cell-cell recognition, adhesion, migration Transport signal to the plasma membrane, or for degradation THESE ROLES are fulfilled by attaching sugars to proteins/lipids.... glycoconjugates

The glycosidic bond (an acetal) between monomers

Is less reactive than the hemiacetal at the second monomer.

Monomer with anomeric carbon involved in the glycosidic linkage

Is nonreducing

Gram-negative bacteria

Lipopolysaccharides -important for antibody recognition

Extracellular matrix (ECM)

Material outside of the cell -strength, elasticity and physical barrier in tissues -connection and communication to interior of cell

Starch

Mixture of two homopolysaccharides of glucose -main storage polysaccharide in plants -amylose and amylopectin

Reducing end (can still open up to form aldehyde)

Monomer with the hemiacetal (still has alpha and beta-anomeric forms)

N-linked glycoprotein

N-glycosyl bond to amide nitrogen of Asn

Polysaccharides

Natural carbohydrates are usually found as polymers -do not have a defined molecular weight -homopolysaccharides -heteropolysaccharides AND -linear -branched

Polymers of approximately 20 or more, with Mws greater than 20kDa

No template to control synthesis (in contrast to proteins) -polymer length is determined by the fidelity of the enzyme

1<--->1 linkage of two pyranoses

Nonreducing

Syndecans

Protein has a single transmembrane domain

Glypicans

Protein is anchored to a lipid membrane

Glycoprotein (glycoconjugate)

Protein with small oligosaccharide attached -typically smaller glycans -found on outside of plasma membrane, organelles, and in blood -form of reversible-covalent post translational modification -recognized by carbohydrate binding proteins (lectins) -Lectins, decipher and translate the 'sugar code'

1-->4 linkage of two pyranoses

Reducing

Cellulase

Secretion by fungi, bacteria and protozoa that allows them to use wood as source of glucose

Beta 1 -->4 linkage

Supports extended structure

Metabolism of cellulose

The fibrous structure and water-insolubility make cellulose a difficult substrate to process -most animals cannot use cellulose as a fuel source because they lack the enzyme to hydrolyze beta 1-->4 linkages (ruminants i.e. sheep and cattle and termites live symbiotically with microorganisms that produce cellulase)

Non-reducing Disaccharides

Two sugar molecules can also be joined via a glycosidic bond between two anomeric carbons -product has two acetal groups and no hemiacetals -there are no reducing ends, this is a nonreducing sugar -prevents formation of longer chains

Glycosidic Bond

Two sugar molecules conjoined between an anomeric carbon and a hydroxyl carbon.

Cellulose

Unbranched homopolysaccharide of glucose -most abundant polysaccharide in nature -glucose monomers form beta 1-->4 linked chains -hydrogen bonds form between adjacent monomers

Amylose

Unbranched polymer of alpha 1-->4 linked residues -nonreducing end and reducing end

1<-->2 linkage of pyranose and furanose

nonreducing