Biochem E2: Carbs

Oligosaccharides

several sugars put together, useful in molecular recognition

Polymers

structure, energy storage

Mixed Polymers

structure, information, nucleic acid backbone

Free Glycans

Signaling, Osmoprotection

Examples of carb polymers providing structure and strength

Plant Cell Wall (cellulose), Bacterial cell wall (peptidoglycan), animal exoskeleton (chitin)

Example of molecular recognition

hemagglutinin on flu and glycosylated host cell receptros

What kinds of chemical interactions are important in carbohydrate mediated recognition events?

H-bonding, many -OH groups on sugars

How can carbohydrates regulate cellular processes?

environmental responses, protein quality control

Example of Environmental Responses regulated by Carbs

nutrient availability controls the reversible covalent modification of proteins with a monosaccharide that causes a change in protein function

Example of Protein Quality Control regulated by Carbs

glycosylated nascent proteins are recognized by chaperones in the ER leading to properly folded proteins

Regioisomers

sugar molecules that have the exact same chemical formula and backbone, but differ in the specific location where a chemical group or linkage

Monosaccharide

basic building block, series of chiral hydroxymethylene units

Chemical Formula of a Carb

Cx(H2O)n with a carbonyl

Aldose

Aldehyde as carbonyl

Ketose

Ketone as carbonyl

What is a very important feature of a monosaccharide for its function?

Its ability to react with itself to form a cyclic hemiacetal. linear and cyclic forms are in equilibrium

Is the linear or cyclic form dominant in solution?

cyclic

What other monosaccharides would you predict to have stable ring forms?

5 or 6 carbon sugars, more or less not favorable

What other cyclic forms of glucose are possible?

stereochem is lost at C1 everytime the sugar interconverts between linear and cyclic form, the OH substituent can be equatorial or axial

Stereochemistry at Carbon 1

Anomeric Center, the a and b forms are in equilibrium

a-D-sugars

C1 and C5 have same configuration, trans on the cyclic ring

B-D-sugars

C1 and C5 have different configuration, cis on the cyclic ring

Impact of anomeric stereochem on structure of saccharides

strongly influences, affects biological function, example is starch (a1-4 glucose) and cellulose (B1-4 glucose)

Epimers

two or more chiral centers and differ in their 3D configuration at only one of those centers

Epimers of glucose

galactose and mannose

What is the most flexible part of the disaccharide structure?

glycosidic bond

Non-reducing end

no free anomeric center

Reducing End

free anomeric center

Where glycans diverge from other biopolymers?

biosynthesis is not templated, not homogenous, depends on expression and localization of glycosyltransferases

Sites of protein Glycosylation

cytoplasm, ER/golgi, mitochondria

where does activation of monosaccharides into nucleotide sugars

cytosol

sugar donors in the activation of monosaccharides into nucleotide sugars

NDP-sugar with UDP, GDP and lipid-sugars

What kinds of glycosylation can occur in ER/Golgi

N-linked glycosylation, O-linked glycosylation

What kinds of glycosylation can occur in mitochondria

O-GlcNAc modification

N-linked glycosylation

attaches glycans to asparagine (Asn) residues within Asn-X-Ser/Thr motifs (not a recognition sequence), on surface of secreted or membrane proteins, processing in ER/golgi

Regulation example with N-glycans

ER lectins recognize N-glycans to promote protein folding

To which amino acids are O-glycans attached?

Serine and Threonine

Where in the cell are the O-glycans attached?

ER and golgi

Where do O-glycosylated proteins end up?

Anchored on the cell surface or exported into extracellular/mucus secretions (such as mucins)

Mucins

O-glycan example, shields cells against physical and chemical damage and infection