Carbohydrates

TOPICS:

Role & Significance of Carbohydrates

Monosacharides

Oligosacharides

Polysacharides

Glyconoconjugates

ROLE OF CARBOHYDRATES

• As a major energy source for living organisms (glucose is a principal energy source in animal and plants)

• As a means of transporting energy (e.g.: sucrose in plant tissues)

• As a structural material (cellulose in plants, chitin in insects, building blocks of nucleotides)

• As a precursor for other biomolecules (purine, pyrimide)

SIGNIFICANCE OF CARBOHYDRATES

• Carbohydrates are the most abundant biomolecules in nature, having a direct link between solar energy and the chemical bond energy in living organisms

• Source of rapid energy production

• Structural building blocks of cells

• Components of several metabolic pathways

• Recognition of cellular phenomena, such as cell recognition and binding (e.g., by other cells, hormones, and viruses)

Carbohydrate: compound contains H, C & O with the composition (CH2O)n (hydrate of carbon) compound that contains alcohol & carbonyl functional group

Carbonyl functional group: >C=O

Adehyde aldose

Ketone ketose

Carbohydrates

cellulose, chitin,

starch, glycogen,

glucoaminoglycans

disaccharides,

glycoproteins

(bacterial cell

walls)

Classification

Carbohydrate

Mono

saccharide

Oligo

saccharide

Poly

saccharide Glyconoconjugates

glucose, fructose

ribose (aldopentose)

deoxyribose

glycoproteins

and

proteoglycans

MONOSACHARIDES

7

Classification of Carbohydrates

I. Number of carbohydrate units monosaccharides: one carbohydrate unit

(simple carbohydrates)

disaccharides: two carbohydrate units

(complex carbohydrates)

trisaccharides: three carbohydrate units

polysaccharides: many carbohydrate units

8

II. Position of carbonyl group at C1, carbonyl is an aldehyde: aldose

at any other carbon,

carbonyl is a ketone: ketose

III. Number of carbons three carbons: triose six carbons: hexose

four carbons: tetrose seven carbons: heptose

five carbons: pentose etc.

Monosacharides

Subsections :

• Properties & classification

• Stereoisomers

• Cyclic structure

• Important Reactions

• Important monosach

• glycoproteins and proteoglycans • Monosaccharide derivatives

Monosach properties & classification

• Colorless, crystalline solids

• Soluble in water but insoluble in nonpolar solvents

• One of the carbon atoms is double-bonded to an oxygen atom to form a carbonyl group; each of the other carbon atoms has a hydroxyl group – Carbohydrates with an aldehyde (-CHO) functional group

are called aldoses e.g. glyceraldehyde (CH2OH-CHOH-CHO)

Those with a keto group (-C=O) are ketoses e.g.dihydroxyacetone

(CH2OH-C=O-CH2OH)

– Classified according to the number of carbon atoms they contain

Monosacharides: examples of aldoses & ketoses

Aldotetrose Aldotriose Aldopentoses

Ketotriose Ketotetrose Ketopentose Ketohexose

Aldohexose

MONOSACCHARIDES STEREOISOMERS

• Isomers: same chemical formulas, different structures

• Conformation: the spatial arrangement of substituent groups

• Chiral centers: asymmetric carbons, i.e carbon atom with four different substituents

• Enantiomers: mirror images stereoisomers

• The simplest aldose, glyceraldehyde, contains one chiral center (the middle carbon atom) and has two different optical isomers, or enantiomers

the projection in which the carbohydrate backbone is

drawn vertically with the carbonyl shown on the top

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

D vs L Designation

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

D & L sugars are mirror images of one another

They have the same name, e.g., D-glucose & L-glucose

Other stereoisomers have unique names, e.g., glucose, mannose, galactose, etc.

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

The 6-C aldoses have 4 asymmetric centers. Thus there are 16 stereoisomers (8 D-sugars and 8 L-sugars)

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

Pyranoses & Furanoses

Pyranoses: six-membered ring compounds (resemble pyran)

Furanoses: fivemembered rings, (resemble furan)

The systematic names of

glucose & fructose become:

HAWORTH STRUCTURES

Cyclic structure of monosacharides

in aqueous solution, monosaccharides with five or more carbon atoms in the backbone occur predominantly as cyclic (ring) structures in which the carbonyl group has formed a covalent bond with the oxygen of a hydroxyl group along the chain

The new chiral center in cyclic (C-1) is called anomeric carbon

18

Mutarotation The - and -anomers are in equilibrium, and interconvert through the open form.

The pure anomers can be isolated by crystallization. When the pure anomers are

dissolved in water they undergo mutarotation, the process by which they return

to an equilibrium mixture of the anomer

-D-Glucopyranose (36%)

(-anomer: C1-OH and

CH2OH are trans)

-D-Glucopyranose (64%)

(-anomer: C1-OH and

CH2OH are cis)

[]D +18.7°

[]D +112.2°

FISHER AND HAWORTH FORMS OF SUGAR

Epimers Sugars that differ only in their stereochemistry at

a single carbon

20

SUMMARY OF SUGAR STRUCTURES

ISOMERS- compounds that have the same chemical formula e.g. fructose, glucose, mannose, and galactose are isomers of each other having formula C6H12O6.

EPIMERS- refer to sugars whose configuration differ around one specific carbon atom e.g. glucose and galactose are C-4 epimers and glucose and mannose are C-2 epimers.

ENANTIOMERS- a special type of isomerism found in pairs of structures that are mirror images of each other. The mirror images are termed as enantiomers and the two members are designated as D- and L- sugar. The vast majority of sugars in humans are D-sugars.

CYCLIZATION OF SUGARS- most monosaccharides with 5 or more carbon atoms are predominately found in a ring form, where the aldehyde or ketone group has reacted with an alcoholic group on the same sugar group to form a hemiacetal or hemiketal ring.

Pyranose ring- if the ring has 5 carbons and 1 oxygen. Furanose ring- if the ring is 5-membered (4 carbons and 1 oxygen

IMPORTANT REACTIONS IN MONOSACCHARIDES

Monosaccharides undergo the following reactions:

1. Oxidation 2. Reduction 3. Isomerization 4. Esterification 5. Glycoside formation

Oxidation in presence of oxidising agents, metal ions

Cu2+) and enzymes, Monosaccharidess undergo several oxidation reactions e.g. • Oxidation of

aldehyde group (R-CHO) yields aldonic acid;

• of terminal CH2OH (alcohol) yields uronic acid;

• and of both the aldehyde and CH2OH gives aldaric acid

24

Oxidation of Monosaccharides. C1 of aldoses can be

selectively oxidized to the carboxylic acid (aldonic acids) with

Br2 or Ag(I) (Tollen’s test), Cu(OH)2 (Trommer’s test), Cu(OH)2 and

tartaric acid (Trommer’s test)

Reducing sugars: carbohydrates that can be oxidized to aldonic

acids.

Oxidation by Bromine

Bromine water oxidizes aldehyde, but not ketone or alcohol; forms aldonic acid.

Oxidation by Tollens Reagent Tollens reagent reacts with aldehyde,

but the base promotes enediol rearrangements, so ketoses react too.

Sugars that give a silver mirror with Tollens are called reducing sugars.

Chapter 23

Problem with Tollens • 2-Ketoses (e.g. fructose) are also oxidized to aldonic

acids in basic solution (Tollens).

An aldoseAn enediolA 2-ketose

CH2 OH

C= O

CH2 OH

C-OH

CH2 OH

CHOH

CHOH

CH2 OH

CHO

( CHOH) n( CHOH) n ( CHOH) n

An aldonic acid

CHOH

CH2 OH

COOH

( CHOH) n

(1) (2) (3)

Ketose to aldose conversion via keto enol

tautomerism

Oxidation

Reducing sugar

REDUCING SUGARS

• All monosacchs are reducing sugars.

• They can be oxidised by weak oxidising agent such as Benedict’s reagent

• Benedict's reagent is a solution of copper sulfate, sodium hydroxide, and tartaric acid.

Aqueous glucose is mixed with Benedict's reagent and heated. The reaction reduces the blue copper (II) ion to form a brick red precipitate of copper (I) oxide. Because of this, glucose is classified as a reducing

sugar.

Benedict’s Test

• Benedict’s reagent undergoes a complex colour change when it is reduced

• The intensity of the colour change is proportional to the concentration of reducing sugar present

• The colour change sequence is: – Blue… – green… – yellow… – orange… – brick red

Nonreducing Sugars • Glycosides are acetals, stable in base, so they

do not react with Tollens reagent.

• Disaccharides and polysaccharides are also acetals, nonreducing sugars.

Oxidation of aldoses to aldaric acids with HNO3.

Uronic Acid: Carbohydrate in which only the terminal -CH2OH is

oxidized to a carboxylic acid.

CHO

CH2 OH

OHH

HHO

OHH

OHH

CHO

COOH

OHH

HHO

OHH

OHH

HOHO

OHOH

COOHO

D-Glucose

enzyme-catalyzed

oxidation

D-Glucuronic acid

(a uronic acid)

.

Reduction of Monosaccharides. C1 of aldoses are

reduced with sodium borohydride to the 1° alcohol (alditols)

34

◦ Other alditols common in the biological world are:

CH2 OH

CH2 OH

OHH

OHH

CH2 OH

CH2 OH

OHH

HHO

OHH

CH2 OH

HHO

HHO

OHH

CH2 OH

OHH

D-Mannitol XylitolErythritol

Epimerization

In base, H on C2 may be removed to form enolate ion. Reprotonation may change the stereochemistry of C2.

=>

IMPORTANT REACTIONS (Cont)

ESTERIFICATION Free OH groups of carbohydrates react with acids to form esters. This

reaction an change the physical and chemical propteries of sugar.

Ester Formation Acetic anhydride with pyridine catalyst converts all the oxygens to acetate

esters.

Chapter 23 37

=>

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

E.g., methanol reacts with the anomeric OH on glucose to form methyl glucoside (methyl-glucopyranose).

O

H

HO

H

HO

H

OH

OHHH

OH

-D-glucopyranose

O

H

HO

H

HO

H

OCH3

OHHH

OH

methyl--D-glucopyranose

CH3-OH+

methanol

H2O

GLYCOSIDE FORMATION

IMPORTANT REACTIONS (Cont)

Glycosidic binds are between two sugars

They can either be in the or configuration

and can be linked through the 1-2, 1-4 or 1-6

linkage

Alpha Beta

• Fermentation. Sugars undergo a chemical change known as fermentation in the presence of enzymes secreted by certain microorganisms.

Alcoholic fermentation is commercially used in making wines, beers, and other alcoholic beverages. Lactose is the only sugar that cannot be fermented, since yeast does not contain the proper enzyme.

IMPORTANT MONOSACCHARIDES

• GLUCOSE

• FRUCTOSE

• GALACTOSE

D-Glucose:

D-glucose (dextrose) is the primary fuel in living cells

especially in brain cells that have few or no mitochondria.

Cells such as eyeballs have limited oxygen supply and use

large amount of glucose to generate energy

Dietary sources include plant starch, and the disaccharides

lactose, maltose, and sucrose

DIABETES (diabetes mellitus) • Characterized by high blood glucose levels that splills over

into the urine

• These high glucose levels impairs the insulin-stimulated glucose entry into cells and starve the cells of insulin.

• This leads to ketosis or high levels of ketone bodies (acids) that hinders the buffering capacity of the blood in the kidney, which controls blood pH (by excreting excess H+ ions into the urine).

• The H+ excretion is accompanied by the excretion ammonia, sodium, potassium, and phosphate ions causing severe dehydration

• This leads to excessive thirst symptom of diabetes and life-threatening decrease in blood volume.

Important monosaccharides. Cont

• FRUCTOSE

– D-fructose (levulose) is often referred as fruit sugar and is found in some vegetables and honey

– This molecule is an important member of ketose member of sugars

– It is twice as sweet as sucrose (per gram basis) and is used as sweeting agent in processed food products

Important monosaccharides. Cont....

GALACTOSE ◦ is necessary to synthesize a variety of

biomolecules (lactose-in mammalary glands, glycolipids, certain phospholipids, proteoglycans, and glycoproteins)

◦ Galactose and glucose are epimers at carbon 4 and interconversion is catalysed by enzyme epimerase.

◦ Medical problems – galactosemia (genetic disorder) where enzyme to metabolize galactose is missing; accumulation of galactose in the body can cause liver damage, cataracts, and severe mental retardation

MONOSACCHARIDE DERVATIVES

URONIC ACIDS – formed when terminal CH2OH group of a mono sugar is oxidised ◦ Important acids in animals – D-

glucuronic acid and its epimer L-iduronic acid

◦ In liver cells glucuronic acid combines with steroids, certain drugs, and bilirubin to improve water solubility therby helping the removal of waste products from the body

◦ These acids are abundant in the connective tissue carbohydrate components.

Mono sugar derivatives

AMINO SUGARS – ◦ Sugars in which a hydroxyl group (common on carbon 2) is replaced by

an amino group e.g. D-glucosamine and D-galactosamine ◦ common constituents of complex carbohydrate molecule found

attached to cellular proteins and lipids ◦ Amino acids are often acetylated e.g. N-acetyl-glucosamine.

Mono sugar derivatives DEOXYSUGARS

◦ monosaccharides in which an - H has replaced an – OH group ◦ Important sugars: L-fucose (formed from D-mannose by reduction reactions) and 2-

deoxy-D-ribose ◦ L-fucose – found among carbohydrate components of glycoproteins, such as those

of the ABO blood group determinates on the surface of red blood cells ◦ 2-deoxyribose is the pentose sugar component of DNA.

GLYCOSIDES

• Monosaccharides can be linked by glycosidic bonds (joining of 2 hydroxyl groups of sugars by splitting out water molecule) to create larger structures.

• Disaccharides contain 2 monosaccharides e.g. lactose (galactose+glucose); maltose (glucose+glucose);

sucrose (glucose+fructose) • Oligosaccharides – 3 to 12 monosaccharides units e.g.

glycoproteins • Polysaccharides – more than 12 monosaccharides units e.g.

glycogen (homopolysaccharide) having hundreds of sugar units; glycosaminoglycans (heteropolysaccharides) containing a number of different monosaccharides species.

DISACCHARIDES

AND

OLIGOSACCHARIDES

DISACCHARIDES AND OLIGOSACCHARIDES

• Cnfigurations: alfa or beta ( 1,4, glycosidic bonds or linkages; other linkages 1,1; 1,2; 1,3; 1,6)

• Digestion aided by enzymes. Defficiency of any one enzyme causes unpleasant symptoms (fermentation) in colon produces gas [bloating of cramps].

• Most common defficiency, an ancestoral disorder, lactose intolerance caused by reduced synthesis of lactase

Important sugars of Disaccharides • LACTOSE

(milk sugar) disaccharide found in milk; composed of one molecule of galactose and glucose linked through beta(1,4) glycosidic linkage; because of the hemiacetal group of the glucose component, lactose is a reducing sugar

Lactose intolerance

Lactose (milk sugar) in infants is hydrolyzed by intestinal enzyme lactase to its component monosacch for absorption into the bloodstream (galactose epimerized to glucose).

Most adult mammals have low levels of beta-galactosidase. Hence, much of the lactose they ingest moves to the colon, where bacterial fermentation generates large quantities of CO2, H2 and irritating organic acids.

These products cause painful digestive upset known as lactose intolerance and is common in the African and Asian decent.

MALTOSE ( malt sugar)

An intermediate product of starch hydrolysis; it is a disaccharide with an alfa(1,4)

glycosidic linkage between two D-glucose molecules; in solution the free

anomeric carbon undergoes mutarotation resulting in an equilibrium mixture of

alfa and beta – maltoses; it does not occur freely in nature

• SUCROSE

common table sugar: cane sugar or beet sugar produced in the leaves and stems of plants; it is a disaccharide containing both alfa-glucose and beta-fructose residues linked by alfa,beta(1,2)glycosidic bond.

• CELLOBIOSE

degradation product of cellulose containing two molecules of glucose linked by a beta (1,4) glycosidic bond; it does not occur freely in nature

58

cellobiose and maltose

are reducing sugar

lactose is a

reducing sugar

sucrose is not

a reducing sugar

Reducing sugars: carbohydrates that can be oxidized to aldonic

acids.

OLIGOSACCHARIDE SUGARS

Oligosaccharides are small polymers often found attached to polypeptides in and some glycolipids.

They are attached to membrane and secretory proteins found in endoplasmic reticulum and Golgi complex of various cells

Two classes: N-linked and O-linked

POLYSACCHARIDES

Intro to Polysaccharides

Classification of Polisacharides

Homosacharides

Heteropolysacharides

Intro to Polysaccharides

• Composed of large number of monosaccharide units connected by glycosidic linkages

• Classified on the basis of their main monosaccharide components and the sequences and linkages between them, as well as the anomeric configuration of linkages, the ring size (furanose or pyranose), the absolute configuration (D- or L-) and any other substituents present.

• Polysaccharides are more hydrophobic if they have a greater number of internal hydrogen bonds, and as their hydrophobicity increases there is less direct interaction with water

• Divided into homopolysaccharides (e.g.Starch, glycogen, cellulose, and chitin) & heteropolysaccharides (glycoaminoglycans or GAGs, murein).

Classification of Polisacharides

HOMOSACCHARIDES

• Found in abundance in nature

• Important examples: starch, glycogen, cellulose, and chitin

• Starch, glycogen, and cellulose all yield D-glucose when they are hydrolyzed

• Cellulose - primary component of plant cells

• Chitin – principal structural component of exoskeletons of arthropods and cell walls of many fungi; yield glucose derivative N-acetyl glucosamine when it is hydrolyzed.

STARCH (Homosaccharide)

A naturally abundant nutrient carbohydrate, (C6H10O5)n, found chiefly in the seeds, fruits, tubers, roots, and stem pith of plants, notably in corn, potatoes, wheat, and rice, and varying widely in appearance according to source but commonly prepared as a white amorphous tasteless powder.

Any of various substances, such as natural starch, used to stiffen cloth, as in laundering.

Two polysaccharides occur together in starch: amylose and amylopectin

Polysaccharides:

Plants store glucose as amylose or amylopectin, glucose polymers collectively called starch.

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.

H O

OH

H

OHH

OH

CH2OH

H

O H

H

OHH

OH

CH2OH

H

O

HH H O

OH

OHH

OH

CH2OH

HH H O

H

OHH

OH

CH2OH

H

OH

HH O

OH

OHH

OH

CH2OH

H

O

H

1

6

5

4

3

1

2

amylose

-amylose

Amylose is poorly soluble in water, but forms micellar suspensions

In these suspensions, amylose is helical

H O

OH

H

OHH

OH

CH2OH

H

O 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

O

1

OH

3

4

5

2

amylopectin

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.

GLYCOGEN (Homosaccharide)

Glycogen is the storage form of glucose in animals and humans which is analogous to the starch in plants.

Glycogen is synthesized and stored mainly in the liver and the muscles.

Structurally, glycogen is very similar to amylopectin with alpha acetal linkages, however, it has even more branching and more glucose units are present than in amylopectin.

Various samples of glycogen have been measured at 1,700-600,000 units of glucose.

The structure of glycogen consists of long polymer chains of glucose units connected by an alpha acetal linkage.

The branches are formed by linking C1 to a C6 through an acetal linkages.

In glycogen, the branches occur at intervals of 8-10 glucose units, while in amylopectin the branches are separated by 12-20 glucose units.

STRUCTURE OF GLYCOGEN

GLYCOGEN (Homosaccharide)

CELLULOSE (Homosaccharide) Cellulose is found in plants as microfibrils (2-20 nm diameter and

100 - 40 000 nm long). These form the structurally strong framework in the cell walls.

Cellulose is mostly prepared from wood pulp

Cellulose is a linear polymer of β-(1 4)-D-glucopyranose units in 4C1

conformation. The fully equatorial conformation of β-linked glucopyranose residues stabilizes the chair structure, minimizing its flexibility

Cellulose has many uses as an anticake agent, emulsifier, stabilizer, dispersing agent, thickener, and gelling agent but these are generally subsidiary to its most important use of holding on to water.

Water cannot penetrate crystalline cellulose but dry amorphous cellulose absorbs water becoming soft and flexible.

Purified cellulose is used as the base material for a number of water-soluble derivatives e.g. Methyl cellulose, carbomethycellulose

Cellulose as polymer of β-D-glucose

Cellulose as polymer of β-D-glucose

CHITIN (Homosaccharide)

Chitin is a polymer that can be found in anything from the shells of beetlesto webs of spiders. It is present all around us, in plant and animal creatures.

It is sometimes considered to be a spinoff of cellulose, because the two are very molecularly similar.

Cellulose contains a hydroxy group, and chitin contains acetamide.

Chitin is unusual because it is a "natural polymer," or a combination of elements that exists naturally on earth.

Usually, polymers are man-made. Crabs, beetles, worms and mushrooms contain large amount of chitin.

Chitin is a very firm material, and it help protect an insect against harm and pressure

Structure of the chitin molecule, showing two of the N-acetylglucosamine units that repeat to form long chains in beta-1,4

linkage.

Chitin is a very firm material, and it help protect e.g. an insect against harm and pressure

CHITOSAN

• Chitin, the polysaccharide polymer from which chitosan is derived, is a cellulose-like polymer consisting mainly of unbranched chains of N-acetyl-D-glucosamine. Deacetylated chitin, or chitosan, is comprised of chains of D-glucosamine. When ingested, chitosan can be considered a dietary fiber.

• Chitosan can be used within the human body to regulate diet programs, and researchers are looking into ways in which it can sure diseases.

CHITOSAN

HETEROPOLYSACCHARIDES

• Are high-molecular-weight carbohydrate polymers more than one kind of monosaccharide

• Important examples include glycosaminoglycans (GAGs) – the principle components of proteoglycans and murein, a major component of bacterial cell walls.

GAGs - high-molecular-weight carbohydrate polymers

• Glycosaminoglycans forming the proteoglycans are the most abundant heteropolysaccharides in the body. They are long unbranched molecules containing a repeating disaccharide unit. Usually one sugar is an uronic acid (either D-glucuronic or L-iduronic) and the other is either GlcNAc or GalNAc. One or both sugars contain sulfate groups (the only exception is hyaluronic acid).

• GAGs are highly negatively charged what is essential for their function.

THE SPECIFIC GAGs OF PHYSIOLOGICAL SIGNIFICANCE

Hyaluronic acid Occurence : synovial fluid, ECM of loose connective tissue Hyaluronic acid is unique among the GAGs because it does not contain any sulfate and is not found covalently attached to proteins. It forms non-covalently linked complexes with proteoglycans in the ECM. Hyaluronic acid polymers are very large (100 - 10,000 kD) and can displace a large volume of water.

Hyaluronic acid (D-glucuronate + GlcNAc)

Dermatan sulfate (L-iduronate + GlcNAc sulfate)

Occurence : skin, blood vessels, heart valves

Heparin and heparan sulfate (D-glucuronate sulfate + N-sulfo-D-glucosamine)

Heparans have less sulfate groups than heparins Occurence : Heparin :component of intracellular granules of mast cells lining the arteries of the lungs, liver and skin

Heparan sulfate : basement membranes, component of cell surfaces

Keratan sulfate ( Gal + GlcNAc sulfate)

Occurence : cornea, bone, cartilage ;

• Keratan sulfates are often aggregated with chondroitin sulfates.