Carbohydrates

Carbohydrates

• Most abundant class of biological molecules on Earth

• Originally produced through CO2 fixation during photosynthesis

Roles of Carbohydrates

• Energy storage (glycogen,starch)

• Structural components (cellulose,chitin)

• Cellular recognition • Carbohydrate derivatives

include DNA, RNA, co-factors, glycoproteins, glycolipids

Carbohydrates

• Monosaccharides (simple sugars) cannot be broken down into simpler sugars under mild conditions

• Oligosaccharides = "a few" - usually 2 to 10

• Polysaccharides are polymers of the simple sugars

Monosaccharides• Polyhydroxy ketones

(ketoses) and aldehydes (aldoses)

• Aldoses and ketoses contain aldehyde and ketone functions, respectively

• Ketose named for “equivalent aldose” + “ul” inserted

• Triose, tetrose, etc. denotes number of carbons

• Empirical formula = (CH2O)n

C

C*

O

C*

C*

CH2OH

H OH

HO H

H OH

H

CH2OH

C

C*

C*

CH2OH

O

HO H

H OH

D-ribose D-ribulose

Monosaccharides are chiral

• Aldoses with 3C or more and ketoses with 4C or more are chiral

• The number of chiral carbons present in a ketose is always one less than the number found in the same length aldose

• Number of possible steroisomers = 2n (n = the number of chiral carbons)

C

C*

O

C*

C*

C*

CH2OH

H OH

HO H

H OH

H OH

H

CH2OH

C

C*

C*

C*

CH2OH

O

HO H

H OH

H OH

D-glucose D-fructose

Stereochemistry

•Enantiomers = mirror images

•Pairs of isomers that have opposite configurations at one or more chiral centers but are NOT mirror images are diastereomers

•Epimers = Two sugars that differ in configuration at only one chiral center

C

C*

O

C*

C*

C*

CH2OH

H OH

HO H

H OH

H OH

H

C

C*

O

C*

C*

C*

CH2OH

HO H

H OH

HO H

HO H

H

C

C*

O

C*

C*

C*

CH2OH

H OH

HO H

H OH

H OH

H

C

C*

O

C*

C*

C*

CH2OH

HO H

HO H

H OH

H OH

H

C

C*

O

C*

C*

C*

CH2OH

HO H

HO H

H OH

H OH

H

C

C*

O

C*

C*

C*

CH2OH

H OH

HO H

HO H

H OH

H

D-glucoseL-glucose

Enantiomers

D-glucose D-mannose

Epimers

D-mannose D-galactose

Diastereomers

Cyclization of aldose and ketoses introduces additional

chiral center• Aldose sugars (glucose) can cyclize to

form a cyclic hemiacetal

• Ketose sugars (fructose) can cyclize to form a cyclic hemiketal

HC

R1

O

OH R2

HO

C*

OR2

R1H

H

ALCOHOL

ALDEHYDE

HEMIACETAL

NEW CHIRAL CARBON

RC

R1

O

OH R2

HO

C*

OR2

R1R

H

ALCOHOL

KETONE

HEMIKETAL

NEW CHIRAL CARBON

Glucopyranose formation

Fructofuranose formation

Monosaccharides can cyclize to form Pyranose / Furanose

forms = 64% = 36%

= 21.5% = 58.5%

= 13.5% = 6.5%

Haworth Projections

Anomeric carbon(most oxidized)

-OH up = beta-OH down = alpha

1

23

4

5

6

For all non-anomeric carbons, -OH groups point down in Haworth projections if pointing right in Fischer projections

C1

C2 OHH

HO

C3

C4

C5

CH2OH

HHO

OHH

OHH

Conformation of Monosaccharides

Pyranose sugars not planar molecules, prefer to be in either of the two chair conformations.

Reducing Sugars

• When in the uncyclized form, monosaccharides act as reducing agents.

• Free carbonyl group from aldoses or ketoses can reduce Cu2+ and Ag+ ions to insoluble products

Derivatives of Monosaccharides

Sugar Phosphates

Deoxy Acids

Amino Sugars

Sugar alcohols

Monosaccharide structures you need to

know1) Glucose2) Fructose3) Ribose4) Ribulose5) Galactose6) Glyceraldehyde

Carbohydrates

• Monosaccharides (simple sugars) cannot be broken down into simpler sugars under mild conditions

• Oligosaccharides = "a few" - usually 2 to 10

• Polysaccharides are polymers of the simple sugars

Glycosidic Linkage

O

CH2OH

OH

OH

OHOH

O

CH2OH

OH

OH

OH

OH

H2OH2O

O

CH2OH

OH

OH

OH

O

O

CH2OH

OH

OH

OH

alcohol

hemiacetal

glycosidic linkage

Hydrolysis

Condensation

acetal

DisaccharidesO

CH2OH

OH

OH

OH

O

O

CH2OH

OH

OH

OHH

H

H

H

H

H

H H

O

CH2OH

OH

OH

OH

O

O

CH2OH

OH

OH

OH

H

H

H

H

H

H

H

H

O

CH2OH

OH

OH

H

O

O

CH2OH

OH

OH

OH

H

OH

H

H

H

H

H

H

maltose cellobiose

lactose

sucrose

-D-glucosyl-(1->4)--D-glucopyranose)

-D-glucosyl-(1->4)--D-glucopyranose)

-D-galactosyl-(1->4)--D-glucopyranose)

-D-glucosyl-(1->2)--D-fructofuranose)

O

CH2OH

OH

OH

OH

H

H

H

H

OCH2OH

H

H

OH

OH

H

O

CH2OH

Higher Oligosaccharides

Oligosaccharide groups are incorporated in to many drug

structures

Polysaccharides• Nomenclature:

homopolysaccharide vs. heteropolysaccharide

• Starch and glycogen are storage molecules

• Chitin and cellulose are structural molecules

• Cell surface polysaccharides are recognition molecules

Starch• A plant storage polysaccharide

• Two forms: amylose and amylopectin

• Most starch is 10-30% amylose and 70-90% amylopectin

• Average amylose chain length 100 to 1000 residues

• Branches in amylopectin every 25 residues (15-25 residues) -1->6 linkages

• Amylose has -1->4 links, one reducing end

Amylose and Amylopectin

Starch

• Amylose is poorly soluble in water, but forms micellar suspensions

• In these suspensions, amylose is helical

Glycogen

• Storage polysaccharide in animals• Glycogen constitutes up to 10% of liver

mass and 1-2% of muscle mass • Glycogen is stored energy for the

organism • Only difference from starch: number of

branches • Alpha(1,6) branches every 8-12 residues • Like amylopectin, glycogen gives a red-

violet color with iodine

Dextrans• If you change the main linkages between

glucose from alpha(1,4) to alpha(1,6), you get a new family of polysaccharides - dextrans

• Branches can be (1,2), (1,3), or (1,4)

• Dextrans formed by bacteria are components of dental plaque

• Cross-linked dextrans are used as "Sephadex" gels in column chromatography

• These gels are up to 98% water!

Dextrans

Cellulose

• Cellulose is the most abundant natural polymer on earth

• Cellulose is the principal strength and support of trees and plants

• Cellulose can also be soft and fuzzy - in cotton

Cellulose vs Amylose

Glucose units rotated 180o relative to next residue

cellulose

amylose

Cellulose

• Beta(1,4) linkages make all the difference!

• Strands of cellulose form extended ribbons

• Interchain H-bonding allows multi-chain interactions. Forms cable like structures.

Chitin• exoskeletons of crustaceans, insects

and spiders, and cell walls of fungi

• similar to cellulose, but instead of glucose uses N-acetyl glucosamine (C-2s are N-acetyl instead of –OH)

-1->4 linked N-acetylglucosamine units

• cellulose strands are parallel, chitins can be parallell or antiparallel

O

CH2OH

NH

OH

H

OH

H

OH

H

H

C O

CH3

Chitin vs Cellulose

Peptidoglycan

• N-acetylglucosamine and N-acetylmuramic acid groups linked -1->4

• Heteroglycan linked to a tetrtapeptide (Ala-IsoGlu-Lys-Ala)

• Gram (-) have petanta- glycine linker to next strand

• Gram (+) have directly cross links to next strand

Peptidoglycan

Peptidoglycan is target of antibacterial agents•Lysozyme = enzyme that cleaves polysaccharide chain of peptidoglycan

•Penicillin = inhibits linking of peptidoglycan chains.

•Inhibits bond formation between terminal alanine and pentaglycine linker

•Penicillian looks like an Ala-Ala

Peptidoglycan and Bacterial Cell Walls

Composed of 1 or 2 bilayers and peptidoglycan shell

• Gram-positive: One bilayer and thick peptidoglycan outer shell

• Gram-negative: Two bilayers with thin peptidoglycan shell in between

• Gram-positive: pentaglycine bridge connects tetrapeptides

• Gram-negative: direct amide bond between tetrapeptides

Glycoproteins

• May be N-linked or O-linked • N-linked saccharides are

attached via the amide nitrogens of asparagine residues

• O-linked saccharides are attached to hydroxyl groups of serine, threonine or hydroxylysine

O-linked Glycoproteins

• Function in many cases is to adopt an extended conformation

• These extended conformations resemble "bristle brushes"

• Bristle brush structure extends functional domains up from membrane surface

O-linked Glycoproteins

N-linked Glycoproteins

• Oligosaccharides can alter the chemical and physical properties of proteins

• Oligosaccharides can stabilize protein conformations and/or protect against proteolysis

• Cleavage of monosaccharide units from N-linked glycoproteins in blood targets them for degradation in the liver

• Involved in targeting proteins to specific subcellular compartments