Carbohydrates

CARBOHYDRATES

polyhydroxy aldehydes and ketones or substances that hydrolyze to yield polyhydroxy aldehydes and ketones.

Most abundant class of biological molecules on Earth

Originally produced through CO2 fixation during photosynthesis

Empirical formula = (CH2O)n

ROLES OF CARBOHYDRATES Energy storage (glycogen,starch) Structural components (cellulose,chitin) Cellular recognition Carbohydrate derivatives include DNA, RNA,

co-factors, glycoproteins, glycolipids

CARBOHYDRATES CLASSIFICATION

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

Oligosaccharides = "a few" - usually 2 to 10 monosaccharides. It is further divided into disaccharides or trisaccharides.

Polysaccharides are polymers of the simple sugars with high molecular weight. It is of two types, Homopolysaccharides and heteropolysaccharides

CLASSIFICATION OF MONOSACCHARIDES

Monosaccharides are classified according to:(1) The number of carbon atoms present in the

molecules.(2) whether they contain an aldehyde or keto group.

Monosaccharides

Aldoses (-HC=O)

Ketoses(-C=O)

Trioses (C3H6O3) Glyceraldehyde Dihydroxyacetone

Tetroses (C4H8O4)

Erythrose Erythrulose

Pentoses (C5H10O5)

Ribose Ribulose

Hexoses (C6H12O6)

Glucose Fructose

MONOSACCHARIDES

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

D VS L DESIGNATION

D & L designations are based on the configuration about the single asymmetric C in glyceraldehyde.

The lower representations are Fischer Projections.

CHO

C

CH2OH

HO H

CHO

C

CH2OH

H OH

CHO

C

CH2OH

HO H

CHO

C

CH2OH

H OH

L-glyceraldehydeD-glyceraldehyde

L-glyceraldehydeD-glyceraldehyde

SUGAR NOMENCLATURE

O H O H

C C

H – C – OH HO – C – H

HO – C – H H – C – OH

H – C – OH HO – C – H

H – C – OH HO – C – H

CH2OH CH2OH

D-glucose L-glucose

For sugars with more than one chiral center, D or L refers to the asymmetric C farthest from the aldehyde or keto group.

Most naturally occurring sugars are D isomers.

CYCLIZATION OF ALDOSE AND KETOSES INTRODUCES ADDITIONAL CHIRAL CENTER Aldose sugars (glucose) can cyclize to form a

cyclic hemiacetal An aldehyde can react with an alcohol to form a hemiacetal.

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

A ketone can react with an alcohol to form a 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

Pentoses and hexoses can cyclize as the ketone or aldehyde reacts with a distal OH.Glucose forms an intra-molecular hemiacetal, as the C1 aldehyde & C5 OH react, to form a 6-member pyranose ring, named after pyran.

These representations of the cyclic sugars are called Haworth projections.

H O

OH

H

OHH

OH

CH2OH

H

OH

H H O

OH

H

OHH

OH

CH2OH

H

H

OH

-D-glucose -D-glucose

23

4

5

6

1 1

6

5

4

3 2

H

CHO

C OH

C HHO

C OHH

C OHH

CH2OH

1

5

2

3

4

6

D-glucose (linear form)

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

Fructose forms either a 6-member pyranose ring, by reaction of

the C2 keto group with the OH on C6, or a 5-member furanose ring, by reaction of

the C2 keto group with the OH on C5.

CH2OH

C O

C HHO

C OHH

C OHH

CH2OH

HOH2C

OH

CH2OH

HOH H

H HO

O

1

6

5

4

3

2

6

5

4 3

2

1

D-fructose (linear) -D-fructofuranose

MONOSACCHARIDES CAN CYCLIZE TO FORM PYRANOSE / FURANOSE FORMS

= 64% = 36%

= 21.5% = 58.5%

= 13.5% = 6.5%

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 ALCOHOLS - LACKS AN ALDEHYDE OR KETONE; E.G…

COOH

C

C

C

C

H OH

HO H

H OH

D-gluconic acid D-glucuronic acid

CH2OH

OHH

CHO

C

C

C

C

H OH

HO H

H OH

COOH

OHH

sugar acid - the aldehyde at C1, or OH at C6, is oxidized to a carboxylic acid; e.g., gluconic acid, glucuronic acid.

SUGAR DERIVATIVES

amino sugar - an amino group substitutes for a hydroxyl. An example is glucosamine.

The amino group may be acetylated, as in N-acetylglucosamine.

H O

OH

H

OH

H

NH2H

OH

CH2OH

H

-D-glucosamine

H O

OH

H

OH

H

NH

OH

CH2OH

H

-D-N-acetylglucosamine

C CH3

O

H

AMINO SUGARS

MONOSACCHARIDE STRUCTURES YOU NEED TO KNOW

Glucose Fructose Ribulose Glyceraldehyde Dihydroxyacetone

GLYCOSIDIC BONDS

The anomeric hydroxyl and a hydroxyl of another sugar or some other compound can join together, splitting out water to form a glycosidic bond:

R-OH + HO-R' R-O-R' + H2O

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

DIASACCHARIDES

H O

O H

H

O HH

O H

CH 2O H

H

O H

O H

H

O HH

O H

CH 2O H

H

O

HH

1

23

5

4

6

1

23

4

5

6

m altose

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

DIASACCHARIDES

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

H O

O H

H

O HH

O H

CH 2O H

H

O O H

H

H

O HH

O H

CH 2O H

H

H

H

O1

23

4

5

6

1

23

4

5

6

cellobiose

DISACCHARIDES

O

CH2OH

OH

OH

H

O

O

CH2OH

OH

OH

OH

H

OH

H

H

H

H

H

H

lactosesucrose

-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

POLYSACCHARIDES(GLYCANS): Linear or Branched polymers

STARCH(Glucosan or Glucan) Plants store glucose as amylose or

amylopectin, glucose polymers collectively called starch.

H O

OH

H

OHH

OH

CH 2 OH

HO H

H

OHH

OH

CH 2 OH

H

O

HH H O

OH

OHH

OH

CH 2 OH

HH H O

H

OHH

OH

CH 2 OH

H

OH

HH O

OH

OHH

OH

CH 2 OH

H

O

H

1

6

5

4

3

1

2

a m y lo s e

Polysaccharides:

Glucose storage in polymeric form minimizes osmotic effects.

Amylose is a glucose polymer with (14) linkages.

The end of the polysaccharide with an anomeric C1 not involved in a glycosidic bond is called the reducing end.

Amylopectin is a glucose polymer with mainly (14) linkages, but it also has branches formed by (16) linkages. Branches are generally longer than shown above.The branches produce a compact structure & provide multiple chain ends at which enzymatic cleavage can occur.

H O

OH

H

OHH

OH

CH2OH

HO H

H

OHH

OH

CH2OH

H

O

HH H O

OH

OHH

OH

CH2

HH H O

H

OHH

OH

CH2OH

H

OH

HH O

OH

OHH

OH

CH2OH

H

O

H

O

1 4

6

H O

H

OHH

OH

CH2OH

HH H O

H

OHH

OH

CH2OH

HH

O1

OH

3

4

5

2

amylopectin

Glycogen, the glucose storage polymer in animals, is similar in structure to amylopectin. But glycogen has more (16) branches. The highly branched structure permits rapid glucose release from glycogen stores, e.g., in muscle during exercise. The ability to rapidly mobilize glucose is more essential to animals than to plants.

H O

OH

H

OHH

OH

CH 2OH

HO H

H

OHH

OH

CH 2OH

H

O

HH H O

OH

OHH

OH

CH 2

HH H O

H

OHH

OH

CH 2OH

H

OH

HH O

OH

OHH

OH

CH 2OH

H

O

H

O

1 4

6

H O

H

OHH

OH

CH 2OH

HH H O

H

OHH

OH

CH 2OH

HH

O1

OH

3

4

5

2

glycogen

Cellulose, a major constituent of plant cell walls, consists of long linear chains of glucose with (14) linkages.Every other glucose is flipped over, due to linkages.

c e l lu lo s e

H O

OH

H

OHH

OH

CH 2 OH

HO

H

OHH

OH

CH 2 OH

HO

H H O

O H

OHH

OH

CH 2 OH

HH O

H

OHH

OH

CH 2 OH

H

H

OHH O

O H

OHH

OH

CH 2 OH

HO

H H H H

1

6

5

4

3

1

2

Multisubunit Cellulose Synthase complexes in the plasma membrane spin out from the cell surface microfibrils consisting of 36 parallel, interacting cellulose chains. These microfibrils are very strong. The role of cellulose is to impart strength and rigidity to plant cell walls, which can withstand high hydrostatic pressure gradients. Osmotic swelling is prevented.Explore and compare structures of amylose & cellulose using Chime.

c e l lu lo s e

H O

OH

H

OHH

OH

CH 2 OH

HO

H

OHH

OH

CH 2 OH

HO

H H O

O H

OHH

OH

CH 2 OH

HH O

H

OHH

OH

CH 2 OH

H

H

OHH O

O H

OHH

OH

CH 2 OH

HO

H H H H

1

6

5

4

3

1

2

Glycosaminoglycans (mucopolysaccharides) are linear polymers of repeating disaccharides. The constituent monosaccharides tend to be modified, with acidic groups, amino groups, sulfated hydroxyl and amino groups, etc.Glycosaminoglycans tend to be negatively charged, because of the prevalence of acidic groups.

H O

H

H

O HH

O H

COO

H

H O

O H H

H

NH COCH 3H

CH 2O H

H

OO

D -g lucuronate

O

1

23

4

5

61

23

4

5

6

N -acetyl-D -g lucosam ine

hyaluronate

Hyaluronate (hyaluronan) is a glycosaminoglycan with a repeating disaccharide consisting of 2 glucose derivatives, glucuronate (glucuronic acid) & N-acetyl-glucosamine. The glycosidic linkages are (13) & (14).

H O

H

H

O HH

O H

COO

H

H O

O H H

H

NH COCH 3H

CH 2O H

H

OO

D -g lucuronate

O

1

23

4

5

61

23

4

5

6

N -acetyl-D -g lucosam ine

hyaluronate

Heparan sulfate is initially synthesized on a membrane-embedded core protein as a polymer of alternating N-acetylglucosamine and glucuronate residues. Later, in segments of the polymer, glucuronate residues may be converted to the sulfated sugar iduronic acid, while N-acetylglucosamine residues may be deacetylated and/or sulfated.

H O

H

OSO3H

OH

H

COOO H

H

NHSO3H

OH

CH2OSO3

H

H

H

O

O

heparin or heparan sulfate - examples of residues

iduronate-2-sulfate N-sulfo-glucosamine-6-sulfate

Heparin, a soluble glycosaminoglycan found in granules of mast cells, has a structure similar to that of heparan sulfates, but is more highly sulfated.

When released into the blood, it inhibits clot formation by interacting with the protein antithrombin.

Heparin has an extended helical conformation.

heparin: (IDS-SGN)5

PDB 1RID

C  O  N  S

Heparin shown has 10 residues, alternating IDS (iduronate-2-sulfate) & SGN (N-sulfo-glucosamine-6-sulfate).

O-linked oligosaccharide chains of glycoproteins vary in complexity. They link to a protein via a glycosidic bond between a sugar residue & a serine or threonine OH. O-linked oligosaccharides have roles in recognition, interaction, and enzyme regulation.

H O

OH

O

H

HNH

OH

CH2OH

H

C CH3

O

-D-N-acetylglucosamine

CH2 CH

C

NH

O

H

serine residue

Oligosaccharides that are covalently attached to proteins or to membrane lipids may be linear or branched chains.

N-linked oligosaccharides of glycoproteins tend to be complex and branched. First N-acetylglucosamine is linked to a protein via the side-chain N of an asparagine residue in a particular 3-amino acid sequence.

H O

OH

HN

H

H

HNH

OH

CH2OH

H

C CH3

O

C CH2 CH

O HN

C

HN

O

HC

C

HN

HC

R

O

C

R

O

Asn

X

Ser or ThrN-acetylglucosamine

Initial sugar in N-linked glycoprotein oligosaccharide

MULTIPLE CHOICE QUESTION 1. Ribose is differ from Deoxyribose in A. C1 B. C2 C. C3 D. C4

2. All are aldose except A. Glucose B. Galactose C. Mannose D. Fructose

3. The glycosaminoglycan that serves as anticoagulant A. Heparin B. Hyaluronic acid C. Chondroitin Sulfate

D. Keratin sulfate

4. Which polysaccharide is composed of b-Glycosidic bonds A. Amylose B. Amylopectin C. Cellulose

D. Glycogen

5. Number of asymmetric carbon atom in glucose is:A. One B. Two C. Three D. Four

MULTIPLE CHOICE QUESTION 6. A homopolysaccharide made up of fructose is:

A. Glycogen B. Starch C. Cellulose D. Inulin

7. Cyclization of the open chain form of glucose produces

A. Hemiacetal B. Anhydride C. Lactone D. Aldehyde

8.Which of the following is an example of a storage polysaccharide made by animals?

A. Cellulose B. Glycogen C. Collagen D. Starch.

9. Cellulose, a b(1->4)-linked glucose polysaccharide, differs from starch in that starch is a 

A. b(1->6)-linked manose polysaccharide

B. b(1->6)-linked glucose polysaccharide.

C. an a(1->6)-linked glucose polysaccharide.

D. an a(1->4)-linked glucose polysaccharide.

E. an a(1->4)-linked mannose polysaccharide.