CARBOHYDRATES: CARBOHYDRATES: STRUCTURE AND STRUCTURE AND FUNCTIONFUNCTION

ObjectivesObjectives

To understand the structure of carbohydrates To understand the structure of carbohydrates of physiological significanceof physiological significance

To understand the main role of carbohydrates To understand the main role of carbohydrates in providing and storing of energy in providing and storing of energy

To understand the structure and function of To understand the structure and function of glycosaminoglycans glycosaminoglycans

OVERVIEWOVERVIEW

The most abundant organic molecules The most abundant organic molecules in naturein nature

– provide important part of energy in dietprovide important part of energy in diet– Act as the storage form of energy in the bodyAct as the storage form of energy in the body– are structural component of cell membraneare structural component of cell membrane

The empiric formula is (CHThe empiric formula is (CH22O)n – O)n –

“hydrates of carbon”“hydrates of carbon”

OVERVIEWOVERVIEW

Diseases associated with disorders Diseases associated with disorders of carbohydrate metabolism: of carbohydrate metabolism:

– Diabetes mellitus Diabetes mellitus

– GalactosemiaGalactosemia

– Glycogen storage diseasesGlycogen storage diseases

– Lactose intoleranceLactose intolerance

CONT’D

CLASSIFICATION:CLASSIFICATION: Monosaccharides:Monosaccharides: Simple sugar Simple sugar

Disaccharides: Disaccharides: 2 monosaccharide 2 monosaccharide unitsunits

Oligosaccharides: Oligosaccharides: 3-10 3-10 monosaccharide unitsmonosaccharide units

Polysaccharides:Polysaccharides: more than 10 more than 10 sugar unitssugar unitsHomopolysaccharides and heteropolysaccharidesHomopolysaccharides and heteropolysaccharides

MonosaccharidesMonosaccharides

Further classifiedFurther classified based on: based on:

1. No. of carbon atoms1. No. of carbon atoms 2. Functional group:2. Functional group:

Aldehyde group – aldosesAldehyde group – aldosesKeto group – ketosesKeto group – ketoses

So

me

So

me

Mo

no

sacc

har

ides

Mo

no

sacc

har

ides

All carbons in a monosaccharide are bonded to a hydroxyl group (-OH) except

for one which is bonded to a carbonyl group  (=O) (note that this statement is true

only for the linear form of monosaccharides)

So

me

So

me

Mo

no

sacc

har

ides

Mo

no

sacc

har

ides

IsomerismIsomerism

IsomersIsomers

Compounds having same Compounds having same chemical formula but chemical formula but different structural different structural formulaformula

The No. of isomers depends The No. of isomers depends on the No. of asymmetric on the No. of asymmetric C C

So

me

So

me

Mo

no

sacc

har

ides

Mo

no

sacc

har

ides

The

tw

o si

mpl

est

suga

rs

Note Numerous Chiral Carbons

Sugar IsomersSugar Isomers

1.1. Aldo-ketoAldo-keto

2.2. EpimersEpimers

3.3. D- and L-FormsD- and L-Forms

4.4. αα- and - and ββ-anomers-anomers

Aldo-Keto IsomersAldo-Keto Isomers

Example:Example:

Glucose and Glucose and fructosefructose

EpimersEpimers EpimersEpimersCHO dimers that differ in CHO dimers that differ in

configuration around configuration around only only one one specific carbon atomspecific carbon atom

-Glucose and galactose, C4-Glucose and galactose, C4

-Glucose and Mannose, C2-Glucose and Mannose, C2

Galactose and mannose Galactose and mannose are are not not epimers, whyepimers, why??

14

Figure: Epimers of glucose.Figure: Epimers of glucose.

Structures that are Structures that are mirror imagesmirror images of each of each other and are other and are designated as D- and designated as D- and L- sugars based on the L- sugars based on the position of –OH grp on position of –OH grp on the the asymmetric asymmetric carbon farthest from carbon farthest from the carbonyl carbonthe carbonyl carbon

Majority of sugars in Majority of sugars in humans are humans are D-sugarsD-sugars

Enantiomers Enantiomers (D- and L-Forms)(D- and L-Forms)

αα- and - and ββ-Forms-Forms

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

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)

Cyclization of Monosaccharides Monosaccharides with 5 or more carbon are predominantly found in the ring form

-The aldehyde or ketone grp reacts with the –OH grp on the same

sugar

-Cyclization creates an anomeric carbon (former carbonyl carbon) generating the α and β configurations

MutarotationMutarotationIn solution, the cyclic In solution, the cyclic αα and and ββ anomers of a anomers of a

sugar are in equilibrium with each other, sugar are in equilibrium with each other, and can be interconverted spontaneouslyand can be interconverted spontaneously

Fischer Projection Haworth Projection

DisaccharidesDisaccharides:: Joining of 2 monosaccharides Joining of 2 monosaccharides by by O-O-

glycosidic bond:glycosidic bond:

Maltose (Maltose (αα-1, 4) = glucose + glucose-1, 4) = glucose + glucose

Sucrose (Sucrose (αα-1,2) = glucose + fructose -1,2) = glucose + fructose

Lactose (Lactose (ββ-1,4) = galactose + glucose-1,4) = galactose + glucose

Lactulose (Lactulose (ββ-1,4) = galactose + fructose-1,4) = galactose + fructose

DisaccharideDisaccharide

DisaccharidesDisaccharides

LactoseLactose

CONT’D

PolysaccharidesPolysaccharides HomopolysaccharidesHomopolysaccharides::

BranchedBranched:: glycogen ( storage in humans) and starch glycogen ( storage in humans) and starch ( plants), both (( plants), both (αα-glycosidic polymer of glucose)-glycosidic polymer of glucose)

UnbranchedUnbranched: cellulose (: cellulose (ββ-glycosidic polymer)-glycosidic polymer)

HeteropolysaccharidesHeteropolysaccharides::

e.g., e.g., glycosaminoglycans (GAGs)glycosaminoglycans (GAGs)

Reducing SugarsReducing Sugars If the If the O on the anomeric CO on the anomeric C of a sugar is not of a sugar is not

attached to any other structure, that sugar can attached to any other structure, that sugar can act act as a reducing agentas a reducing agent

RReducing sugars reduce chromogenic agents educing sugars reduce chromogenic agents like like Benedict’s reagentBenedict’s reagent or or Fehling’s solutionFehling’s solution to give a colored periceptateto give a colored periceptate

UUrine is tested for the presence of reducing rine is tested for the presence of reducing sugars using these colorimetric testssugars using these colorimetric tests

Reducing SugarsReducing Sugars

Examples:Examples:

MonosaccharidesMonosaccharides

Maltose and LactoseMaltose and Lactose

Sucrose is non-reducing, Why?Sucrose is non-reducing, Why?

CONT’D

Complex CarbohydratesComplex Carbohydrates Carbohydrates attached to non-carbohydrate Carbohydrates attached to non-carbohydrate

structures by glycosidic bonds (O- or N-type) structures by glycosidic bonds (O- or N-type) e.g.e.g.

11. . Purine and pyrimidine bases in nucleic acidsPurine and pyrimidine bases in nucleic acids

2. Aromatic rings in steroids2. Aromatic rings in steroids

3. Proteins in glycoproteins and glycosaminoglycans3. Proteins in glycoproteins and glycosaminoglycans

4. Lipids found in glycolipids4. Lipids found in glycolipids

5. Bilirubin5. Bilirubin

Glycosidic BondsGlycosidic Bonds

N-GlycosidicN-Glycosidic

O-Glycosidic

Glycosaminoglycans (GAGs)Glycosaminoglycans (GAGs) GlycosaminoglycansGlycosaminoglycans (GAGs) are large complexes of (GAGs) are large complexes of

negatively charged heteropolysaccharidenegatively charged heteropolysaccharide chains chains are associated with a small amount of protein, forming are associated with a small amount of protein, forming

proteoglycansproteoglycans, which consist of over 95 percent , which consist of over 95 percent carbohydratecarbohydrate

bind with large amounts of water, producing the gel-like bind with large amounts of water, producing the gel-like matrix that forms body's ground substance matrix that forms body's ground substance

The viscous, lubricating properties of mucous secretions The viscous, lubricating properties of mucous secretions also result from GAGs, which led to the original naming also result from GAGs, which led to the original naming of these compounds as of these compounds as mucopolysaccharidesmucopolysaccharides

Glycosaminoglycans (GAGs)Glycosaminoglycans (GAGs) GAGs GAGs are are linear polymerslinear polymers of of repeating repeating disaccharidedisaccharide units units

[acidic sugar-amino sugar] n [acidic sugar-amino sugar] n The amino sugar (The amino sugar (usually sulfatedusually sulfated) is ) is either either

D-glucosamine or D-galactosamineD-glucosamine or D-galactosamine The acidic sugar is either The acidic sugar is either

D-glucuronic acid or L-iduronic D-glucuronic acid or L-iduronic acidacid GAGs are strongly negatively-charged: GAGs are strongly negatively-charged: carboxyl groups of acidic sugarscarboxyl groups of acidic sugars & & Sulfate groupsSulfate groups

Resilience of GAGsResilience of GAGs Being negatively charged GAG chains are Being negatively charged GAG chains are

extended in solution and repel each other and extended in solution and repel each other and when brought together, they "slip" past each when brought together, they "slip" past each otherother

This produces the This produces the ""slippery" consistency of slippery" consistency of mucous secretions and synovial fluidmucous secretions and synovial fluid

When a solution of GAGs is compressed, the When a solution of GAGs is compressed, the water is "squeezed out" and the GAGs are water is "squeezed out" and the GAGs are forced to occupy a smaller volume. When the forced to occupy a smaller volume. When the compression is released, the GAGs spring back compression is released, the GAGs spring back to their original, hydrated volume because of to their original, hydrated volume because of the repulsion of their negative chargesthe repulsion of their negative charges

This property contributes to the This property contributes to the resilience of resilience of synovial fluid and the vitreous humor of synovial fluid and the vitreous humor of the eyethe eye

Examples of GAGs are:Examples of GAGs are:

1.1. Chondroitin sulfatesChondroitin sulfates

2.2. Keratan sulfatesKeratan sulfates

3.3. Hyaluronic acidHyaluronic acid

4.4. HeparinHeparin

Members of GAGsMembers of GAGs

CHONDROITIN SULFATESCHONDROITIN SULFATES

Disaccharide unit:Disaccharide unit: Sulfated Sulfated N-acetyl-galactosamine N-acetyl-galactosamine

+Glucuronic acid+Glucuronic acid

MostMost abundantabundant GAG in the GAG in the bodybody

Form proteoglycan Form proteoglycan aggregatesaggregates

Found in cartilage, tendons, Found in cartilage, tendons, ligaments, and aortaIn ligaments, and aortaIn cartilage, they bind collagen cartilage, they bind collagen and hold fibers in a tight, and hold fibers in a tight, strong networkstrong network

KERATAN SULFATESKERATAN SULFATES Disaccharide unit:Disaccharide unit:

N-acetylglucosamine N-acetylglucosamine

Galactose Galactose ((no uronic acidno uronic acid)) Sulfate content is variable Sulfate content is variable

and may be present on C-6 and may be present on C-6 of either sugarof either sugar

Most heterogeneous GAGsMost heterogeneous GAGs Present in loose Present in loose

connective tissue and connective tissue and corneacornea

HYALURONIC ACIDHYALURONIC ACID Disaccharide unit:Disaccharide unit:

N-acetylglucosamine N-acetylglucosamine

Glucuronic acidGlucuronic acid Different from other GAGs: Different from other GAGs:

UnsulfatedUnsulfated

Not covalently attached to proteinNot covalently attached to protein

The only GAG found in The only GAG found in bacteriabacteria

Serves as a lubricant and shock Serves as a lubricant and shock absorberabsorber

Found in synovial fluid of joints, Found in synovial fluid of joints, vitreous humor of the eye, the vitreous humor of the eye, the umbilical cord, and cartilageumbilical cord, and cartilage

HEPARINHEPARIN Disaccharide unit:Disaccharide unit:

Glucosamine and Glucosamine and

Glucuronic or iduronic acidsGlucuronic or iduronic acids Sulfate is found on Sulfate is found on

glucosamine and uronic acid glucosamine and uronic acid Unlike other GAGs that are Unlike other GAGs that are

extracellular, heparin is an extracellular, heparin is an intracellularintracellular component of component of mast cells that line arteries, mast cells that line arteries, especially liver, lungs and especially liver, lungs and skinskin

Serves as Serves as anticoagulantanticoagulant