carbohydrates and glycobiology carbohydrate function and classification monosaccharides –chemical...

Carbohydrates and Glycobiology• Carbohydrate function and classification• Monosaccharides

– Chemical structure and properties– Linear and cyclized forms– Common monosaccharides and disaccharides

• Carbohydrates can be joined to phosphates, alcohols and amines– Hexose derivatives important in biology

• Polysacchardies: Glycogen, Starch, Cellulose, and Chitin

“The chemistry and biology of carbohydrates has been a Cinderella field: an area that involves much work but, alas, does not get to show off at the ball with her cousins, the genomes and proteins.”

Stella Hurtley, Robert Service, Phil Szuromi, Science Vol 291, 23 March 2001

“What has rescued this Cinderella from the shadows is no fairy godmother but a plethora of new synthetic and analytic methods that a previous generations of researchers would have found nearly magical nonetheless.”

“Glycobiology has finally become part of the mainstream”

• Functions: – As energy stores and fuels– As metabolic intermediates– As part of many important molecules (ATP, ribose sugar..)

– In polysaccharides (e.g. cell walls of bacterial and plant) – Linked to proteins and lipids (glycoconjugates)

• In the extra cellular milieu, they exert effects on cellular recognition in infection, cancer, and immune response.

• Carbohydrates are central to many processes that are at the core of important diseases drug design targeting a wide spectrum of diseases

• Classification: mono- and polysaccharides

Carbohydrates

• Two families of monosaccharides– Aldehydes with multiple OH groups (aldose)

– Ketones with multiple OH groups (ketose)

• Chemical structures of monosaccharides– Triose, tetrose, pentose, hexose, heptose

• Smallest one: (CH2O)3

e.g.: D(L)-glyceraldehyde

• Hexoses are the most common monosaccharides in nature

• D-ribose and 2-deoxy-D-ribose are components of nucleotides and nucleic acids

– All except one monosaccharides have asymmetric centers

• Fisher projection representation

• Perspective representation

Monosaccharides

Cyclized forms are predominant for pentoses and hexoses • Furanose (hemiacetal): cyclized pentose

• Pyranose (hemiketal): cyclized hexose

• Haworth projections

• Anomers

• Conformation of pyranose/furanose rings

– Pyranose ring: Chair vs. boat form

– Furanose ring: puckered

• Common monosaccharides– D-ribose, D-glucose, D-mannose,

D-galactose, D-fructose

• Common disaccharides and enzymes that hydrolyze them– Sucrose: glucose-fructose (sucrase)

– Lactose: galactose-glucose (lactase)

– Maltose: glucose-glucose (maltase)

– Enzymes are located on epithelial cells lining the small intestine

• Many monosaccharides are reducing agents

Common Monosaccharides and Disaccharides

• Lactose intolerance: lack of lactase

• Sugars can be phosphorylated– Key intermediates in energy generation and biosynthesis

• Carbohydrates can be joined to alcohols and amines by glycosidic bonds– N-glycosidic

– O-glycosidic

• Important hexose derivatives in biology (next slide)

Carbohydrates Can be Joined to Phosphates, Alcohols and Amines

Some hexose derivatives important in biology

a uronic acid a aldonic acid

Polysaccharides: Glycogen

• Polysaccharides

– Homosaccharides (branched and unbranched)

– Heterosaccharides (branched and unbranched)

• Glycogen

– Store of glucose in animal cells 14 linkage with 16

branch

– Exist in granules inside the cell tightly bound with enzymes for glycogen synthesis and degradation

Polysaccharides: Starch

• Starch – Store of sugar in plants

– Two forms

• Amylose: unbranched

– Glucose, -1,4 linkage

• Amylopectin: branched

– Glucose, 1 -1,6 per 30 -1,4 -amylase: hydrolyze -1,4 linkages

Curved Polysaccharide Chain in amylose-Unbranched Starch

Polysaccharides: Cellulose and Chitin• Cellulose

– Plant polysaccharide

– Serve as a structural not nutritional role

– Unbranched polymer of glucose, -1,4 linkages

– Linear chains; forming fibers; high tensile strength

– Mammals lack cellulases and so cannot digest wood and vegetable fibers

• Chitin

– Exoskeletons of insects

– Unbranched polymer of NAG, -1,4 linkages

– Long straight chains; structural roles

Intra-chainH-bonds

Inter-chainH-bonds

Linear Structure of Cellulose (D-glucose Linkage)

Extended chain

Give extended chain

Bacterial Cell Walls Contain Peptidoglycans

Structure of the cell wall ofstaphylococcus aureus

NAG: N-acetylglucosamineNAM: N-acetylmuramic acid

1 4 linkage

A number of layers;Provide strength to the cell;Keep shape of the cell;

Antibacterial agent act on cell wall –peptidoglycan;Pennicillin; Lysozyme

Glycosaminoglycans are components of the extracellular matrix

the extracellular spacein the tissues of

multicellular animals

a gel-like materialHeteropolysaccharide;linear

Repreating disaccharides;

N-acetylglucosamine (NAG) orN-acetylgalactosamine;

Uronic acid (in most cases): D-glucuronic acid, or L-iduronic acid

C-6 carbon in glucose/galactose/mannose is oxidized to carboxyl

One or more –OH is esterified with sulfate

High density of negative charges on glycosaminoglycans(-COO-, -OSO3

-)

extendedconformation

In some glycosaminoglycans,The amino sugar is

esterified with sulfate

Uronic acid(most cases)

NAG or N-acetylgalactosamine

High density of negative charges

extended conformation in solution

Glycosaminoglycans are attached To extracellular proteins to

form proteoglycans

Very long!

short

short

Hyaluronate

Chondroitin4-sulfate

Keratin sulfate