structure and function of carbohydrates (sugars) azin nowrouzi (phd) anowrouzi@tums.ac.ir

STRUCTURE AND FUNCTION OF CARBOHYDRATES (SUGARS)

Azin Nowrouzi (PhD)anowrouzi@tums.ac.ir

Overview: The Molecules of Life

• All living things are made up of four classes of large biological molecules:

1. Carbohydrates2. lipids3. Proteins4. nucleic acids

• Within cells, small organic molecules are joined together to form larger molecules

• Macromolecules are large molecules composed of thousands of covalently connected atoms

• Molecular structure and function are inseparable

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Many Important Biomolecules are Polymers

p ro te in com plex

p ro te in su b un it

a m ino ac id

m em b rane

p ho sp ho lip id

fa tty a c id

ce ll w a ll

ce llu lo se

g lu co se

ch ro m o som e

D N A

n uc leo tidemonomer

polymer

supramolecularstructure

lipids proteins carbo nucleic acids

• A condensation reaction or more specifically a dehydration reaction occurs when two monomers bond together through the loss of a water molecule

• Enzymes are macromolecules that speed up the dehydration process

• Polymers are disassembled to monomers by hydrolysis, a reaction that is essentially the reverse of the dehydration reaction

The Synthesis and Breakdown of Polymers

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig. 5-2

Short polymer

HO 1 2 3 H HO H

Unlinked monomer

Dehydration removes a watermolecule, forming a new bond

HO

H2O

H1 2 3 4

Longer polymer

(a) Dehydration reaction in the synthesis of a polymer

HO 1 2 3 4 H

H2OHydrolysis adds a watermolecule, breaking a bond

HO HH HO1 2 3

(b) Hydrolysis of a polymer

Fig. 5-2a

Dehydration removes a watermolecule, forming a new bond

Short polymer Unlinked monomer

Longer polymer

Dehydration reaction in the synthesis of a polymer

HO

HO

HO

H2O

H

HH

4321

1 2 3

(a)

Fig. 5-2b

Hydrolysis adds a watermolecule, breaking a bond

Hydrolysis of a polymer

HO

HO HO

H2O

H

H

H321

1 2 3 4

(b)

Carbohydrates (sugars)

• Most abundant macromolecules in nature

Functions:• Energy Storage• Structure• Cellular Recognition• DNA Backbone

Classification of Sugars

• Monosaccharides simple sugars• Polyalcohols• Aldehyde, ketone• Common formula: (CH2O)n = CnH2nOn when n≥3• They contain C, H, and O

• Monosaccharides are classified by three characteristics:① The location of the carbonyl group (as aldose or ketose)

② The number of carbons in the carbon skeleton (Based on number of carbons (3, 4, 5, 6), a monosaccharide is a triose, tetrose, pentose or hexose.

③ Chiral handedness

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Disaccharides - 2 monosaccharides covalently linked.Oligosaccharides - a few monosaccharides covalently

linked. Polysaccharides - polymers consisting of chains of

monosaccharide or disaccharide units.

• Aldotriose• Ketotriose• Aldotetrose• Ketotetrose• Aldopentose• Ketopentose• ….

Aldoses

Enantiomers = mirror images

D vs L Designation enantiomers = mirror images

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

Optical activity measured by polarimeter

Temperature T (given in degrees Celsius) and wavelength λ (in nanometers). If the wavelength of the light used is 589 nanometer (the sodium D line), the symbol “D” is used.

Some examples: Sucrose +66.47°Lactose +52.3°Cholesterol −31.5°Penicillin V +223°Fructose -92.4 degreesGlucose +52.5 degrees

D-Aldose Tree

Carbohydrates - Stereochemistry

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.

• put most oxidized carbon at top• continue carbon chain to bottom• non-hydrogen substituent on right=D

• The number of stereoisomers is 2n, where n is the number of asymmetric centers.

Optical activity

Racemic solution Meso compound

Simple ketoses

• Ketotetrose• Ketopentose• Ketohexoses: D-fructose

-Fructose helps add to your weight.

-Can cause you to have a chance in getting diabetes.

-Can cause blood clots

-Can damage the liver

-Weakens the immune system

Cyclic sugar structures; Haworth projections

• internal hemiacetal formationan alcohol group adds to the carbonyl

Hemiacetal & hemiketal formation

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

A ketone can react with an alcohol to form a hemiketal.

O C

H

R

OH

O C

R

R'

OHC

R

R'

O

aldehyde alcohol hemiacetal

ketone alcohol hemiketal

C

H

R

O R'R' OH

"R OH "R

+

+

Hemiacetal formation (mechanism)

Cyclization of glucose produces a new asymmetric center at C1. The 2 stereoisomers are called anomers, a & b.

Haworth projections represent the cyclic sugars as having essentially planar rings, with the OH at the anomeric C1:

a (OH below the ring) b (OH above the ring).

H O

OH

H

OHH

OH

CH2OH

H

-D-glucose

OH

H H O

OH

H

OHH

OH

CH2OH

H

H

OH

-D-glucose

23

4

5

6

1 1

6

5

4

3 2

furanose: a 5-membered ring pyranose: a 6-membered ring

Because of the tetrahedral nature of carbon bonds, pyranose sugars actually assume a "chair" or "boat" configuration, depending on the sugar.

The representation above reflects the chair configuration of the glucopyranose ring more accurately than the Haworth projection.

O

H

HO

H

HO

H

OH

OHHH

OH

O

H

HO

H

HO

H

H

OHHOH

OH

-D-glucopyranose -D-glucopyranose

1

6

5

4

32

β-D-Glucopyranose = +19α-D-Glucopyranose = +112At equilibrium = +52°

Mutarotation of glucose

• the two stereoisomers at the hemiacetal (anomeric) carbon

• alpha anomer: OH group is down (Haworth)

• beta anomer: OH group is up (Haworth)anomers are diastereomers (different physical properties)

Fructose forms eithera 6-member pyranose ring, by reaction of the C2 keto group with the OH on C6, ora 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

GlycosylationGlycosidic bond• a glycosidic bond is a type ofcovalent bond that joins a carbohydrate (sugar) molecule to another group, which may or may not be another carbohydrate

Methyl α-D-glucopyranoside

O-glycoside

N-glycoside

Glycosylation of hemoglobin

Sugar derivatives

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

CH2OH

C

C

C

CH2OH

H OH

H OH

H OH

D-ribitol

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 derivatives

Reduction of Aldehyde or ketone

Oxidation of alcohol at C-6

Oxidation of aldehyde group

Oxidation at both ends

Deoxy sugars

L-Rhamnose

Amino sugars

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

N-acetylneuraminate (N-acetylneuraminic acid, also called sialic acid) is often found as a terminal residue of oligosaccharide chains of glycoproteins.

Sialic acid imparts negative charge to glycoproteins, because its carboxyl group tends to dissociate a proton at physiological pH, as shown here.

NH O

H

COO

OH

H

HOH

H

H

RCH3C

O

HC

HC

CH2OH

OH

OH

N-acetylneuraminate (sialic acid)

R =

Sialic acid

• Metastatic cancer cells often express a high density of sialic acid-rich glycoproteins. This overexpression of sialic acid on surfaces creates a negative charge on cell membranes. This creates repulsion between cells (cell opposition) and helps these late-stage cancer cells enter the blood stream.

Phosphate ester derivative

Sulfate esters

D-Galactose 4-sulfate sodium salt

Glycosaminoglycans (GAGs) or MucopolysaccharidesHeteropolysaccharides

• long unbranched heteropolysaccharides• Consist of a repeating disaccharide unit• Repeating disaccharide unit = a hexose (or hexouronic acid linked to a hexosamine.

• In the Golgi apparatus, GAG disaccharides are added to protein cores to yield proteoglycans except hyaluronan

Hyaluronic acid

1T3 glycosidic bonds in b configuration

The repeating disaccharides are linked by 1T4 linkages in b

configuration

IdoUAβ1-3'GalNAcβ1-4

-Gal(6S)β1-4GlcNAc(6S)β1-3

GlcUAβ1-3'GalNAcβ1-4

Chondroitin Sulfate

GlcUAβ1-3'GalNAcβ1-4

D-glucuronic acid (GlcA) and N-acetyl-D-galactosamine (GalNAc).

Types of chondroitin sulfate

"Chondroitin sulfate B" is an old name for dermatan sulfate, and it is no longer classified as a form

of chondroitin sulfate.

Dermatan sulfate• Dermatan sulfate is a glycosaminoglycan• Distinguished from chondroitin sulfate by the presence of iduronic

acid• It was called a mucopolysaccharide• Is found mostly in skin, also in blood vessels, heart valves, tendons,

and lungs• May have roles in coagulation, cardiovascular disease,

carcinogenesis, infection, wound repair, and fibrosis

IdoUAβ1-3'GalNAcβ1-4

Keratan sulfate• Keratan sulfate (KS), also called keratosulfate• any of several glycosaminoglycans (structural carbohydrates) that have

been found in the cornea, cartilage, and bones• It is also synthesized in the central nervous system • Participate both in development and in the glial scar formation after

injury• Are highly hydrated molecules which in joints can act as a cushion to

absorb mechanical shock• The basic repeating disaccharide unit within keratan sulfate is -3Galβ1-

4GlcNAcβ1-• Keratan sulfate occurs as aproteoglycan (PG) in which the chains are

attached to cell-surface proteoglycan (PG) in which KS chains are attached to extracellular matrix proteins, termed core proteins

-Gal(6S)β1-4GlcNAc(6S)β1-3

Heparin

• a highly sulfated glycosaminoglycan

• widely used as an injectable anticoagulant

• Highest negative charged density of any known biological molecule

• One unit of heparin (the "Howell Unit") is an amount approximately equivalent to 0.002 mg of pure heparin, which is the quantity required to keep 1 mL of cat's blood fluid for 24 hours at 0 °C

-IdoUA(2S)α1-4GlcNS(6S)α1-

Proteoglycan

Cellulose