Some Carbohydrate Functions

• Developmental processes• Protein localization• Regulation of activity• Cell-cell interactions• Structural integrity, e.g. cell walls• Phytohormones• Plant and animal defense• Prevention of desiccation (bacteria)• Adherence of bacteria to surfaces• Bacterial resistance to host defenses• Cell-cell recognition and signaling

Introduction to CarbohydratesBiochemistry

Garrett & GrishamChapter 7, p. 209-237

Cn (H2 O)n

C

CHOH

CH2OH

OCH2OH

( )n

Poly-hydroxy-ketone

C

CHOH

CH2OH

OH

( )n

Poly-hydroxy-aldehyde

Monosaccharides

C

CHOH

CH2OH

OH

C

CHOH

CHOH

OH

CHOH

CHOH

CH2OH

C

CHOH

CHOH

OH

CHOH

CH2OH

C

CHOH

CHOH

OH

CH2OH

12

3

12

3

1

23

12

34

5

65

4

4

Aldose family

C

CHOH

CHOH

CHOH

CH2OH

O

CH2OH

C

CHOH

CHOH

CH2OH

O

CH2OH

C

CHOH

CH2OH

O

CH2OH

C

CH2OH

O

CH2OH12

3

12

3

4

1

2

3

5

4

1

2

3

4

5

6

Ketose family

Stereo-isomerism

D-glyceraldehyde L-glyceraldehyde

1

32

C

CHOH

CH2OH

OH

CHO

HOHHOCH2

CHO

CH2OHH

CHO

OHHOCH2

H

CHO

CH2OHHOH

CHO

CH2OH

OHHCHO

CH2OH

HHO

HO

COH

HOCH

CH2OH

R S

D-glyceraldehyde

D-threose D-erythrose

D-lyxose D-xylose D-arabinose D-ribose

D-talose D-galactose D-idose D-gulose D-mannose D-glucose D-altrose D-allose

C

CHOH

CH2OH

OH

C

HCOH

HCOH

OH

HCOH

HCOH

CH2OH

C

HOCH

HCOH

OH

HCOHHCOH

CH2OH

C

HCOHHOCH

OH

HCOH

HCOH

CH2OH

CHOCH

HOCH

OH

HCOH

CH2OH

HCOH

COH

HCOH

HCOH

HOCH

HCOH

CH2OH

COH

HOCH

CH2OH

HCOH

HOCH

HCOH

COH

HCOH

HOCH

CH2OH

HCOH

HOCH

COH

HOCH

HOCH

HOCH

HCOH

CH2OH

HOCH

CH2OH

HCOH

HOCH

COH

HCOH

HOCH

HCOH

CH2OH

COH

HOCH

HCOH

HCOH

CH2OH

COH

HCOHHCOH

HCOH

CH2OH

COH

CH2OH

HCOH

HOCH

COH

HCOH

HCOH

CH2OH

COH

D-Aldoses

D-Ketoses

dihydroxyacetone

D-erythrulose

D-xylulose D-ribulose

D-tagatose D-sorbose D-fructose D-psicose

CH2OH

C

HCOH

HCOH

HCOH

CH2OH

O

CH2OH

C O

HOCH

CH2OH

HCOH

HCOH

CH2OH

C

HCOH

O

HOCH

CH2OH

HCOH

CH2OH

C O

HOCH

HCOH

CH2OH

HOCH

HOCH

CH2OH

HCOH

C

CH2OH

O

HCOH

HCOH

CH2OH

C O

CH2OH

HCOH

CH2OH

C O

CH2OH

CH2OH

C O

CH2OH

Hemi-acetal (ketal)

R CO

HO C R'

H

R C O

H

C R'

C

C

C

C

C

CH2OH

OH

H OH

HO H

H OH

H OH

C

C

C

C

C

CH2OH

H OH

HO H

H OH

H

H

O

OH C

C

C

C

C

CH2OH

H OH

HO H

H OH

H

HO

O

H

Anomers

α-D-glucose D-glucose β-D-glucose

HO

Haworth Structures

C

C

C

C

C

CH2OH

H OH

HO H

H OH

H

H

O

OH

OHOH

CH2OH

H

OHH

H

HO OH

H O

OH

CH2OH

OHHO OH

O

C

C

C

C

CH2OH

H CH2OH

HO H

H OH

H

O O

CH2OH

OH

H

HO

OH

HH

HOCH2 O

CH2OH

OH

HO

OH

HOCH2

O

Fischer

Haworth

pyran

furan

α-D-glucopyranose

β-D-fructofuranose

Conformations

OHOH

CH2OH

H

OHH

H

HO H

OHO

H

OH

H

OHH

HO

H

HOCH2OH

O

OH

H

OH

H

OH

HOH

H

CH2OH

H(e)

(a)4C1

1C4

envelope (E) twist (T)

4C14C1

Various Glycosyl Residues

O

OH

CH2OH

HO HO OH

O

OH

CH2OH

OH

HOOH

O

OH

COOH

OHHO

OH

O

OH

COOH

OH

HOOH CHOH

HCOH

CH2OH

NH COOH

OHH

HOH

H3CC

OO

OH

HO

OH

COOHH

H

HOCH

CH2OH

OH

OHHO

OHOH

D-Mannose D-Galactose D-Glucuronic acid

D-Galacturonic acid N-Acetylneuraminic acid(Sialic acid)

3-Deoxy-D-manno-2-octulosonic acid

myo-inositol

β-L-Rhamnose

O

H

OH

H

H3C

HOHO

OH6-deoxy-β-L-mannose

O

OH

CH2OH

HOHO

OH O

HOOHOH

HOHOCH2

O

HOOHOH

HOCH3 O

OH

CH3

HO

HO

OH

D-mannose L-mannose

O

OH

H

H

OHOH

H

OH

HCH3

HO

H

OH

OH

HH

HO

H

HO

H

CH2OH

β-D-Man

O

H

OH

H

H3C

HOHO

OH

Mutarotation

O

OH

CH2OH

HO

HO O

H

H

H+

O

OH

CH2OH

HO

HO

OHOH

OH

CH2OH

HO

HOC

O

H

H+

α βopen chain

Initial state 1

aqueous solution ofD-glucose with X g/ml and a specificrotation of +112.2o

Initial state 2

aqueous solution ofD-glucose with X g/ml and a specificrotation of +18.7o

Final state for both

equilibrium solutionwith a specificrotation of +18.7o

Some Reactions

C

HCOHHOCH

OH

HCOH

HCOH

CH2OH

CH2OH

HCOHHOCH

HCOH

HCOH

CH2OH

CH2OH

HCOHHOCH

HOCH

CH2OH

HCOH

C

HCOHHOCH

OH

HOCH

CH2OH

HCOH

COOH

HCOHHOCH

HCOH

HCOH

CH2OH

C

HCOHHOCH

HCOH

HC

CH2OH

O

O

C

HCOHHOCH

OH

HCOH

HCOH

COOH

COOH

HCOHHOCH

HCOH

HCOH

COOH

O

OH

CH2OH

OHHO OH

O

OH

CH2OH

OHHO OCH3

CH3OH

H+

H2OH+

Reduction

D-glucitol(sorbitol)

D-galactitol(dulcitol)

D-gluconic acid D-gluconlactone D-glucuronic acid D-glucaric acid

Oxidation

Glycoside formation

methyl-α-D-glucose (methyl-α-D-glucopyranoside)

O

OH

CH2OH

OH

HO

OH

O

OH

CH2OH

OHHO OH

O

OH

CH2OH

OHOH

OHO

OH

CH2OH

OH

O

OHOCH2

HO

HOCH2OH

O

OH

CH2OH

OHHO O

O

OH

CH2OH

OHHO

OO

CH2OH

H

HO

OH

HH

HOCH2

Oligosaccharides

A B4-O-β-galactopyranosyl-α-D-glucopyranose(lactose)

2-O-α-D-glucopyranosyl-β-D-fructofuranoside(sucrose)

A B

BB

B

A

A

A

Adenosine

O

HOOH

HOCH2

NH2

N

N

N

N

N-Glycosidic bond

PolysaccharidesO

OH

CH2OH

OH

OOO

OH

CH2OH

OH

O

O

OH

CH2OH

OH

O

O

OH

CH2OH

OH

O

OCH2OH

NH

OHO

O O

OH

COOH

OH

O

CCH3O

OCH2OH

NH

OHO

O

OH

COOH

OH

O

CCH3O

O

OH

CH2OH

OHOO

O

OH

CH2OH

OHO

O

OH

CH2

OHO

O

O

OH

CH2OH

OHO

O

OH

CH2OH

OH

O

OCH2OSO3

-

NH

O

CCH3O

OH

O

OH

COO-

OH

O

OCH2OSO3

-

NH

O

SO3-

OHO O

OSO3-

COO-

OH

O

Cellulose (a homopolysaccharide)

Starch

Hyaluronic acid(a heteropolysaccharide)

Heparan sulfate

D-Glc + ATP D-Glc-6-P + ADP

D-Glc-6-P D-Glc-1-P

D-Glc-1-P + UTP UDP-Glc + PPi

2Pi

“Activated” Sugar Donors

O

HOOH

CH2

O

HN

N

O

O

P O-O

OP

O

-O

O

O

OH

CH2OH

OH

HO

NDP-sugar pyrophosphorylase(UDP-glucose pyrophosphorylase)

UDP-Glc

UDP-Gal

UDP-GlcA

UDP-GalA

GDP-Man

GDP-Fuc

UDP-GlcNAc

dTDP-Glc

ADP-Glc

dTDP-Rha

CMP-Kdo

CMP-NeuNAc

ADP-Hep

Sugar Nucleotide Biosynthesis

UDP-Glc Gal-1-P Glc-1-PUDP-Gal+ +

UDP-Glc UDP-GlcA

NAD+ NADPH2 2

UDP-GlcA UDP-GalA

dTDP-D-Glc dTDP-L-Rha

GDP-D-Man GDP-L-Fuc

galactose 1-phosphate uridylyltransferase (galT)

UDP-glucose dehyrogenase

H2O + + 2H+

UDP-glucuronic acid 4-epimerase

UDP-Glucose 4-Epimerase(galE)

UDP-Glc UDP-GalO

OH

CH2OH

OHUDPHO

O

OH

CH2OH

OHUDP

O

NADP+

NADPH

NADPH

NADP+

O

OH

CH2OH

OHUDP

HO

dTDP-L-Rhamnose Biosynthesis

dTDP-D-Glc

dTDP-4-dehydro-6-deoxy-D-Glc

dTDP-4-dehydro-6-deoxy-L-Man

H2OdTDP-glucose 4,6-dehydratase (rfbB)

dTDP-4-dehydrorhamnose 3,5-epimerase (rfbC)

NADPH

NADP+

dTDP-4-dehydrorhamnose reductase (rfbD)

dTDP-L-Rha

dTDP-Rhamnose Biosynthesis:Reaction Mechanism

O

OH

CH2

OHO

H

OH

H

H O dTDPEnz

NAD+

B:

O

OH

CH2

OH

OH

HOO dTDP

EnzNADH

B:

O

OH

CH2

OH

OH

-OO dTDP

O

OH

CH2

OH

OH

OO dTDP

-

+HB

O

OH

CH2

OH

OO dTDP

Enz

NAD

B:

:H

O

OH

CH3

OH

-OO dTDP

+HBO

OH

CH3

OH

OO dTDP

H

O

OH

CH3

OHO dTDP

HHO

O

OH

CH3

OH

OO dTDP

HO

OH

CH3

OHO dTDP

HOO

OH

CH3

OH

OO dTDP

H

O

OH

CH3

OHO dTDP

HHO

dTDPdTDP--glucose 4,6glucose 4,6--dehydratasedehydratasedTDPdTDP--44--dehydrorhamnose dehydrorhamnose 3,53,5--epimeraseepimerasedTDPdTDP--44--dehydrorhamnosedehydrorhamnosereductasereductase

Biosynthesis of CMP-NeuNAc and -Kdo

CMP-NeuNAc CMP-KdoUDP-GlcNAc

UDP-ManNAc

ManNAc

NeuNAc

CMP-NeuNAc

UDP-GlcNAc 2-epimerase

(UDP-ManNAc hydrolase)

UDP

pyr.NeuNAc lyase

PEP

Kdo-8-P

Ara-5-P

Pi

Kdo-8-P aldolase (kdsA)

Kdo-8-P phosphatase

Pi

KdoCTP

PPi

Kdo cytidyltransferase(kdsB)

CMP-KdoCTP

PPi

NeuNAc cytidyltransferase

OHOH

HOCH

H

HHH

HO

O

COOH

P

O

O-

O CH2

OHOH

O

O N

HN

CH2OH Kdo forms a highenergy ketal bondmaking the CMPa very good leavinggroup.

Glycosyl Transferase ReactionsO

HOH

CH2OH

H

OHH

H

HO O UDP

OHOH

CH2OH

H

OH

H

H

HO O

H

P O P O( )n

OHOH

CH2OH

H

OHH

H

HO O P O P O Rib U

O O

O- O-

:X R

OHOH

CH2OH

H

OHH

H

HO

X R

+P O P O Rib U

O O

O- O-

-O

OHOH

CH2OH

H

OHH

H

HO

B Enz

OHOH

CH2OH

H

OHH

H

HO

B Enz

+ P O P O Rib U

O O

O- O-

-O

OHOH

CH2OH

H

OHH

H

HO O P O P O Rib U

O O

O- O-

:X R

OHOH

CH2OH

H

OHH

H

HO X R

:B Enz

+ :B Enz

UDP-Glc Man-DolFormation of β-linkages Formation of α-linkages

:X-R where :X can be a hydroxyl, amine, amide, phosphate,and R can be a sugar, lipid, protein, etc.