Carbohydrates (Chapter 22)

(1)

Carbohydrates

(Chapter 22)

• Introduction

• Classification of Carbohydrates

• Carbohydrates are polyhydroxy aldehydes or ketones or

substances that hydrolyze to yield polyhydroxy aldehydes and ketones

carbohydrates

Ch. 22.1

ketones

• C_n(H₂O)_n

• Monosaccharides cannot be hydrolyzed to simpler carbohydrates

• Disaccharides can be hydrolyzed to two monosaccharides

• Oligosaccharides yield 2 to 10 monosaccharides

(2)

Carbohydrates serve a variety of biological

functions:

• Structural (cellulose in plants)

carbohydrates

Ch. 22.1

• Structural (cellulose in plants)

• Energy (Sugars, starches, ATP)

(3)

_{Monosaccharides}

_{Classification of Monosaccharides}

_{Monosaccharides are classified according to:}

_{(1) The number of carbon atoms, and}

_{(2) whether they contain an aldehyde or ketone group, and} _{(3) stereochemistry}

carbohydrates

(4)

_{Different Ways of Drawing Monosaccharides}

_{Fischer projections} _{are used to represent stereochemistry in}

carbohydrates

_{horizontal lines project out of the plane toward the reader and vertical lines}

project behind the plane

_{(cannot be removed from the plane of the paper or turned 90}o _{- that will change}

the stereochemistry)

carbohydrates

(5)

_{Stereochemistry - D and L Designations}

_{The simplest aldose is glyceraldehyde, which is chiral}

(+)-glyceraldehyde (D)-glyceraldehyde

(-)-glyceraldehyde (L)-glyceraldehyde

carbohydrates

Ch. 22.2

_{Historically, (+)-glyceraldehyde was given the stereochemical} designation (D) and (-)-glyceraldehyde was designated (L) (It was later found that (D)-glyceraldehyde is the R_{-stereoisomer.)}

_{Important to remember the D and L don’t correspond to}d _andl

d _andl _{correspond to (+) and (-)}

(6)

[

α

] = +13.5

o

[

α

] = -13.5

o

OH

H

CHO

CH

₂

OH

D-glyceraldehyde

CHO

CH

₂

OH

H

Fischer projection

CHO

CH₂OH OH H H O H OH H OH H CHO

CH₂OH OH H H O H H O H OH H D-glucose D-galactose

Chapter 16 6

[

α

] = -13.5

o

H

O

H

CHO

CH

₂

OH

L-glyceraldehyde

CHO

CH

₂

OH

H

O

H

CHO

CH₂OH H O H OH H H O H H O H CHO

(7)

_{A monosaccharide whose highest numbered stereogenic center} has the same configuration as D-(+)-glyceraldehyde is a D-sugar, otherwise it is an L-sugar

carbohydrates

Ch. 22.2

(8)

(9)

Configurations of Aldoses

(10)

Diastereomers that differ in configuration at only one

asymmetric carbon are called epimers

(11)

_{Cyclic (Hemiacetal) Forms}

_{Glucose exists primarily in two cyclic hemiacetal forms that are diastereomers}

of each other

_{cyclic forms interconvert via the open-chain form}

_{the mechanism for converting between hemiacetal and aldehyde forms}

are the same as already discussed - both acid- & base-catalyzed

CHO

OH

H

O

H

carbohydrates

Ch. 22.2

O

OH

CH

₂

OH

H

O

H

OH

H

OH

H

D-glucose

O

HO

OH

(12)

(13)

_{Cyclic (Hemiacetal) Forms}

_{two forms differ only in configuration at C1, and are}

O HO HO OH OH OH O HO HO OH OH OH OH HO HO OH O OH β-glucose (β-glucopyranose)

64%

α-glucose (α-glucopyranose)

36%

open chain form (linear form) 0.02% O HO HO OH OH OH glucose

=

carbohydrates Ch. 22.2

_{two forms differ only in configuration at C1, and are}

called anomers

_{C1 is called the anomeric carbon (“carbonyl carbon)}

In D sugars:

_α

_{-anomer has the C1 hydroxyl trans to the -CH}

₂

_OH

group ("down")

_β

_{-anomer is cis ("up")}

_{the anomeric configuration can be left unspecified}

(14)

_{Stereochemistry - Epimers}

_{definition of an epimer - two diastereomers that differ from each} other at a single chiral centre are epimers.

_{several common sugars are epimers of each other}

O

HO

OH

O

HO

OH

O

HO

OH

HO

carbohydrates

Chapter 16 14

β

-glucose

β

-mannose

(2-epimer of glucose)

β

-galactcose

(4-epimer of glucose)

O

OH

HO

OH

ribose

O

OH

HO

OH

arabinose

(15)

_{Haworth formulae} _{give a flat cyclic representation of} carbohydrates

Haworth formula of glucose

carbohydrates

Ch. 22.2

_{a slightly more realistic picture shows a}_{chair conformation}

O HO

HO

OH OH OH

(16)

_{Relationship between drawing methods}

down - right - alpha

carbohydrates

For D carbohydrates

Chapter 16 16

_{hydroxyl being down in Haworth or chair conformation is the} same as being on the right in a Fischer projection

_{"alpha" and "beta" only applies to the anomeric carbon}

up - left - beta

(17)

_Mutarotation

_α_α_α_α_{- and}_β_β_β_β_{-glucose can be isolated separately as solids} _{specific rotation -} _α_α_α_α_{-glucose: +112}o

β ββ

β-glucose: +19o

_{in aqueous solution, the specific rotation of both anomers slowly changes to}

+53o

_{this is mutarotation, the change in optical rotation as an equilibrium mixture of}

anomers forms

_{mutarotation of glucose results in an equilibrium mixture of 36%}_α_α_α_α_{-glucose and}

64% ββββ-glucose

carbohydrates Ch. 22.3 O HO HO OH OH OH O HO HO OH OH OH OH HO HO OH O OH β-glucose (β-glucopyranose)

64%

α-glucose (α-glucopyranose)

36%

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_{5 & 6 Membered Rings}

_{5-membered ring = furanose} _{6-membered ring = pyranose}

O

OH

HO

OH

ribofuranose (20%)

OH

O

HOHO

_OH

glucofuranose (1%)

carbohydrates

Chapter 16 18

O

HO

OH

glucopyranose (99%)

O

HO

OH

ribopyranose (80%)

(19)

_{Important Monosaccharide Structures}

_{know these structures:}

(20)

Formation of Glycosides

The acetal (or ketal) of a sugar is called a glycoside

Chapter 16 20

(21)

(22)

Many O_{-glycosides are monosaccharides joined through acetal functional} groups (i.e. they are polyacetals)

O HO

HO

O OH OH

O HO

OH OH

OH

reducing end

non-reducing end

carbohydrates

Ch. 22.4

Chapter 16 22

_{have a "reducing end" and a "non-reducing end"}

_{(monosaccharides and reducing oligo/polysaccharides will reduce Ag}+_{to Ag}0_{(the silver}

mirror test) under basic conditions, like all other aldehydes)

OH OH

maltose

(23)

Sucrose is considered non-reducing

O

HO

OH

O OH

OH

sucrose

(

α

-

D

-glucopyranosyl-(1->2)-

β

-

D

-fructofuranose)

carbohydrates Ch. 22.4

glucose

furanose

1 2 4 5 6 1 2 5

Nature employs enzymes to create

glycosides

O_{-glycosides are biosynthesized in the reducing}_non-reducing direction

_{often joined to other macromolecules (glycoproteins, glycolipids)}

HO

O

OH

(

α

-

D

-glucopyranosyl-(1->2)-

β

-

D

-fructofuranose)

(24)

_{Starch (energy storage in plants)}

_{glucose homopolymer, composed}

mainly of

α

(1

_{4) glycosidic bonds}

carbohydrates

Ch. 22.13

Nature makes a variety of polysaccharides: precisely made and

broken down by specific enzymes

Chapter 16 24

_{storage form of glucose in plants}

(energy)

_{two forms are amylose (mainly}

α

(1

_{4) linkages) and amylopectin}

(which also contains

α

(1

_{6) branch}

(25)

(26)

carbohydrates

Ch. 22.13

Chapter 16 26

_{Amylose adopts a compact}

(27)

(28)

_Glycogen

_{major carbohydrate storage}

molecule in animals (energy)

_{put together by glycogen}

synthase

_{similar to amylopectin but far}

carbohydrates

Ch. 22.13

Chapter 16 28

_{similar to amylopectin but far}

more branching

_{highly branched nature}

(29)

OH

_Cellulose

_{cellulose chains are relatively straight, can hydrogen bond with} each other to give the rigid, insoluble fibers found in plant cell walls (structural)

_{the resulting sheets then stack on top of each other}

carbohydrates

Ch. 22.13

O O

HO

OH O_HO O OH O OH

n

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_{Peptidoglycan}

_{composes bacterial cell walls}

_{repeating NAG-NAMA disaccharide (in blue, below) is cross-linked} through the peptide portion to make a 3-dimensional mesh that gives cells their mechanical strength (structural)

_{peptidoglycan biosynthesis is the target of many antibiotics}

_{lysozyme is a glycosylase that hydrolyzes peptidoglycan - one of} humans' major defences against bacteria in tears, saliva, etc.

carbohydrates

Chapter 16 30

_{NAG =}N_{-acetyl glucosamine} _{NAMA =}N_{-acetyl muramic acid}

O O

HO

NH O OH

O O

NH O OH

n

peptidoglycan (poly(NAG(β1->4)NAMA)

O

peptide-NH

O

(31)

_{Glycoproteins (eukaryotes) and lipopolysaccharides}

(bacteria) can have very elaborate

O

_-glycoside

structures.

Eukaryotic

_N

-linked

glycosylation

G = glucose M = mannose

N = N-Ac glucosamine

:/ /f re e s p a c e .v ir g in .n e t/ r. b a rc la y /s c h m rs tr .g if h tt p :/ /b io .w in o n a .e d u /b e rg /I L L U S T /c o re c a rb .g if

Variation in bacterial

lipopolysaccharide

carbohydrates :/ /f re e s p a c e .v ir g in .n e t/ r. b a rc la y /s c h m rs tr .g if h tt p :/ /b io .w in o n a .e d u /b e rg /I L L U S T /c o re c a rb .g if

lipopolysaccharide

GlcN = N-Ac glucosamine Glc = glucose

(32)

N

_-glycosides

_{occur in RNA, DNA, nucleosides, nucleotides, cofactors}

(e.g., NAD

+

_{, FAD)}

_{the only common}

N

_{-glycosides have aromatic aglycons}

_like

O

_{-glycosides, they are base stable, acid labile}

_{cannot protonate N atom that is part}N_{-glycoside bond, must} protonate elsewhere in the ring for acid catalyzed cleavage

NH₂ O NH₂

H+ NH2

carbohydrates

Ch. 25.2

Structures H+_{-catalyzed hydrolysis}

Chapter 16 32

N N N N O OH OH HO NH N N N O OH OH O P O O -O P O -O O P O O --_O NH2 N NH2 O N O O P O O-DNA O O -P O O -DNA-O NH O O N O O P O O-RNA O O -P O O -RNA-O OH adenosine GTP

deoxycytidine in DNA uridine in RNA

N N N N O OH OH HO adenosine N N N H N O OH OH HO H+ N N N H N NH2 O OH OH HO H2O

(33)

_{Glycosidase mechanisms}

_{acetals are extremely stable in water because alcohols}

are poor leaving groups and water is a poor nucleophile.

For spontaneous hydrolysis, t

_1/2

= 5 million years

_{enzymes use acid- and base-catalysis simultaneously to}

catalyze reactions much more effectively than either

alone

_{acid catalysis makes electrophilic sites more electrophilic and} increases the leaving group ability of leaving groups

_{base catalysis makes nucleophiles more nucleophilic}

carbohydrates

_{base catalysis makes nucleophiles more nucleophilic}

HO O HO OH O OH R O -_O HO O R HO O HO OH O OH H O HO R -_O O R H O H general base catalysis general acid catalysis