CARBOHYDRATES

BIOCHEMISTRY I
 Structure

• Polyhydroxy compounds (poly-alcohols) that contain a carbonyl (C=O)

group (polyhydroxyaldehides, respectively polyhydroxyketones or
substances that liberate such compounds by hydrolysis)

• Are, in general, ternary substances, constituted of C, H şi O.

• Cn (H2O)n, “carbon hydrates”

• Some carbohydrate molecules do not correspond to this criteria (i.e.

deoxyribose) or contain also other elements (N in hexosamines),
that infirm the old denomination, which is not use today.

• Role of carbohydrates:
– predominantly energetic, both as substrate for oxidations, and as
chemical forms of deposits of energy (80% from human caloric
intake);
– Precursors in the synthesis of other compounds
– constitutive elements of some cellular or tissue structures
Classification

• Oses or monosaccharides (single sugar unit)

• osides, carbohydrate molecules constituted of two or
more monosaccharides
Osides are classified in:
- oligosaccharides, 2 - 10 residues
- polysaccharides, >10 monosaccharide units.

Polysaccharides are classified in:

- homopolycarbohydrates (homopolyglycans),
constituted exclusively of identical monosaccharides
- heteropolycarbohydrates (heteropolyglycans), two
types of different subunits, usually modified
monosaccharides
Monosaccharides

• Nonhydrolysable carbohydrates. Cn(H2O)n, n ≥ 3 (up to 9)

• Are polyalcohol of aldehydes – name aldose – or of ketones -
ketoses

Name:- triose (3C), tetrose (4C), pentose (5C), hexose (6C)

- For each of such molecule there are structures type aldose and
type ketose.
In nature, more spread are hexoses, but
- aldopentoses nucleic acids,
- trioses, tetroses, pentoses and heptoses appear as intermediates
in the carbohydrates metabolism.
 CHO

CHO * C H OH

CHO * C H OH * C H OH

CHO * C H OH * C H OH * C H OH

* C H OH * C H OH * C H OH * C H OH

C H 2O H C H 2 OH C H 2 OH C H 2 OH

CHO

CHO CO

C H 2 OH CO * C H OH

C H 2 OH CO * C H OH * C H OH

CO * C H OH * C H OH * C H OH

C H 2 OH C H 2 OH C H 2 OH C H 2 OH
 Stereoisomerism of monosaccharides

Izomers

Constitutional Izomers Stereoizomers

Conformational Izomers Configurational Izomers

Diastereoizomers Enatiomers

cis-trans Izomers Diastereoizomers with stereogenic center

• Racemic mixture = an equimolecular
mixture of the D and L-enantiomers (equal
number of moles) → no optical activity
 Stereoisomerism of monosaccharides

1 CHO
1 CHO

*C *
H OH HO C H
2 2

C H 2O H C H 2 OH
3 3

D(+)-glyceraldehyde L(-)-glyceraldehyde

CHO CHO CHO CHO

H C OH HO C H H C OH HO C H

H C OH HO C H H C H H C OH

C H 2 OH C H 2 OH C H 2 OH C H 2 OH

eritrose enantiomers treose enantiomers

 CHO

H C OH

C H 2OH

D-(+)-glyceraldehyd

CHO CHO

H COH HO CH

H COH H COH

C H 2OH C H 2O H

D-eritrose D-treose

CHO CHO CHO CHO

H C OH HO CH HCOH HO CH

H C OH H C OH HOCH HOCH

H C OH H C OH HCOH H COH

C H 2OH C H 2O H C H 2O H C H 2O H

CHO CHO CHO CHO CHO CHO CHO CHO

H COH HO CH H C OH HO CH H COH HO CH HC OH HO CH

HCOH HC OH HO CH HO CH HCOH HC OH H OC H HO CH

HCOH HC OH H C OH H COH H OC H HO CH H OCH HO CH

HCOH HC OH H C OH H COH HCOH H C OH HC OH H COH

C H 2OH C H 2OH C H 2OH C H2 O H C H 2OH C H 2OH C H 2O H 2 CH OH

D-alose D-altrose D-glucose D-manose D-gulose D-idose D-galactose D-talose

• Aldoses: ribose, glucose, galactose and manose

• Epimers: Diastereoisomers that differ only by

the configuration of a single asimetric carbon
atom
• Ketoses: ribulose, fructose and sedoheptulose
CYCLIC STRUCTURES OF MONOSACCHARIDES

Glycosidic -OH

Anomers = Isomers that differ at a new asymmetric

carbon atom formed on ring closure
 Cyclic structures of monosaccharides
O OH
C C C H 2 OH C H 2 OH
H H
( C H OH )n ( C H O H )n O C O C
OH
C H OH CH ( C H OH )n ( C H OH )n
O
C H OH CH

Cyclisation to aldoses (5C and 6C) cyclisation to ketoses (6C)

OH
CH C
C H 2 OH H
CH C H C OH
CH O
OH
CH O HOCH O H OC H O
CH2
CH H C OH H C OH
CH
HC HC HC
HC

C H 2O H C H 2O H

furan fructofuranose pyran glucopyranose

 OH
CH C
C H 2 OH H
CH C H C OH
CH O
OH
CH O HOCH O H OC H O
CH2
CH H C OH H C OH
CH
HC HC HC
HC

C H 2O H C H 2O H

furan fructofuranose pyran glucopyranose

CYCLIC STRUCTURES OF MONOSACCHARIDES

Glycosidic -OH

Anomers = Isomers that differ at a new asymmetric

carbon atom formed on ring closure
Mutarotation fenomenon
Mutarotation fenomenon
 Monosaccharides Properties

Physical properties:
- polar character (hydrophilic)
- solid, crystallized substances.
- soluble in water and insoluble in organic solvents
- Solids, decompose before melting
- sweet taste, with unequal intensity:
- fructose – 100%
- glucose - 50%
- galactose - 25%;
- insipide monosaccharides (no taste)
- bitter sensation (taste)
Chemical properties :
- –OH alcoholic functions
- –OH glycosidic function of carbonyl carbon atom, in
solution
- the simultaneous presence of these functions can
confer new properties

From the point of view of medical biochemistry, important

are
- the properties that serve to their identification and
determination,
- the understanding of their metabolic significances.
• Chemical properties :

- Esters formation
- Amines formation
- Oxidation
- Reduction
- Condensation of monosaccharides (di-
and polysaccharides formation)
- glycosylation
• Phosphoric esters of monosaccharides

C H 2 O PO 3 H 2

O
H H

CH 2 OH H
CH O
OH H
CH O H C O
OH OH

CH 2 O PO 3 H 2 CH 2 O PO 3 H 2
H OH

ester 3–phosphate of ester 3–phosphate of ester D–glucose–

glyceraldehide dihydroxyacetone 6–phosphate
• glycoside formation: α-, β-glycosides
• deoxymonosaccharide formation
CHO CHO

HC OH HO CH

HC OH HC OH

HO CH HC OH

HO CH HO CH

CH3 CH3

2–dezoxy–D–ribose L-Ramnose L-Fucose

• aminosuggars formation
• Reducing of the carbonyl group

CHO C H 2 OH C H 2 OH

H C OH H C OH C O

H OC H +H2 H OC H - H2 H OC H

H C OH H C OH H C OH
- H2 + H2
H C OH H C OH H C OH

C H 2 OH C H 2 OH C H 2 OH

glucose sorbitol fructose

Oxidation of aldoses to the terminal groups
(C1 and Cn+2)
CH O

( C H OH ) n

C H 2 OH
C OOH aldoza CH O
aldose
( C H OH ) n ( C H OH ) n

C H 2 0H C OOH

Aldonic acid
acid aldonic Alduronic
acid acid
alduronic

C OOH

( C H OH ) n

C OOH

acid. aldaric
Aldaric acid
Solutions of cupric ion (known as Fehling's solution) provide a simple
test for sugars such as glucose. Sugars that react are called reducing
sugars; those that do not are called nonreducing sugars.
 C OOH C OOH
O
5 H C OH
H
H
H OC H
4 1 (H , OH )
OH H
H C OH
OH 3 2
H C OH
H OH
C H 2 OH

α(β)-glucuronic acid gluconic acid

α-D-iduronic acid
• Glycosylation –the reaction between mono or
oligosaccharides and proteins→glycated proteins

Oligosaccharides
• Derivatives of monosaccharides, by the
condensation of 2-10 monosaccharide molecules.
• The most important natural oligosaccharides are
the disaccharides.
• General formula of disaccharides is Cn(H2O)n-1
 Disaccharides

• maltose α-glucopyranosido-4-α-glucopyranose, reducing

sugar, α- (1-4)- glycosidic bond

• lactose β-galactopyranosido-4-α-glucopyranose, reducing

sugar, β - (1-4)- glycosidic bond
• Sucrose: α-1-glucopyranosido-2-β-fructofuranose,
nonreducing sugar, α- (1-2)- glycosidic bond

• Celobiose: β-glucopyranosido-4- β-glucopyranose,

reducing sugar, β-(1-4)-glycosidic bond
 Polysaccharides

• homopolysaccharides (or homoglycans), constituted of

a large number of monomeric units of a single type

• heteropolysaccharides (or heteroglycans), which

contain two (or more) types of monomeric units,
usually, monosaccharide derivatives, and which are
regularly repeated

• As role:
– Constitution of some structures (for example,
cellulose, mucopolysaccharides of conjunctive
tissues, polysaccharides it the constitution of cellular
membranes, etc.)
– Realize carbohydrate deposits (for example starch,
in vegetables, glycogen in animal tissues).
 Homoglycans
• Starch (C6H10O5)n
– amylose (15-20%) - α(1→ 4)glycosidic bonds
– Linear, soluble in hot water, blue colour with I2

– amylopectine (80-85%) - α(1→4) and α(1→6)glycosidic

– Branched chain, insoluble in water, red colour with I2

Glycogen (C6H10O5)n - α(1→4) and α(1→6)glycosidic

Branched chain, insoluble in water
Cellulose : β-D-glucose.
- the most abundant polysaccharide in nature, found in the
constitution of plantes.
- in humans cannot be degraded by digestion, because
digestive enzymes do not hydrolyses it, therefore in the
digestive tube has the role on undigestive mass (with
mechanic action).
Dextran : α-glucose bound 1,6-α-glycozidic and branches at 1-3 -α-
linkages
• Synthesized from sucrose by lactic acid bacteria such as
Leuconostoc mesenteroides and S. mutans
• It is used to replace blood plasma
• Resin called Sephadex - in analytical biochemistry in processes of
separation by gel-filtration chromatography.

Dextrins : (α-D-glucose) formed during partial starch hydrolysis.

Inulin is a fructosan (residuses of fructose)

• Found in roots of some plantes (dahlia, dandelion, turnip, etc).
• Soluble in warm water.
• Used in physiological investigation to determine the speed of
glomerular filtration.

Chitin : N-acetyl-D-glucosamine, bound by β(1→4)-glycosidic bonds

• characteristic to invertebrates (exoskeleton of insects and
crustaceans)
 Heteroglycans
Glycosaminoglycans (GAG) – mucopolysaccharides

- found mainly in conjunctive tissues

-linear macromolecules, containing a large number (100-1000) of
“repetitive units”
- A repetitive unit contains:
- an uronic acid, D-glucuronic acid, rarely L-iduronic acid
- a hexosamine (glucosamine or galactosamine) N-acetylated
(rarely sulphatated);
- sulphate esterifications
- associated with the structural elements of the tissues such as
bone, elastin and collagen
- hold large quantities of water in interstitial space ⇒ lubricants
- role in binding of calcium ions
- can be covalently bound to proteins, forming proteoglycans
- 8 types of mucopolysaccharides
 Hyaluronic acid
- found in umbilicus cordon,
vitreous corpus, in the
fundamental substance of lax
conjunctive tissue, synovial fluid,
and other organs.
D-glucuronic acid + D-
glucosamine-N-acetylated

Chondroitin sulphates
- more pronounced acidic
character.
- found in cartilage, bones

D-glucuronic acid + D-
galactosamine-N-acetylated, 4 or
6-sulphatated
 Keratan sulphates
- Found in cartilage and cornea.
- their content increases with age

D-galactose + D-glucosamine-
N-acetylated, 6-sulphated

Dermatan sulphates
- found in lungs, tendons, skin,
cartilages.
- Their concentration increases
with age

L-iduronic acid + D-galactosamine-

N-acetylated, 4-sulphated
 Heparin
Heparan sulphates

2-sulphate-D-glucuronic acid + D-glucosamine-N-acetylated

(sulphated)-6-sulphate (Heparan sulphaye has a higher content in
sulphate)

- product of secretion of mastocytes.

- non uniform structure
- antithrombinic action ⇒ anticoagulant
- Having a strong negative character, it increases the negativity of
blood vessels, preventing the formation of thrombus
-cofactor of the enzyme lipoproteinlipase acting as
" clarification factor "
 GLYCOPROTEINS
• Glycoproteins –protein constituent is the
largest component by weight
• Proteoglycans – protein is conjugated to a
particular type of polysaccharide called
glycosaminoglycan (carbohydrate make up a
larger percentage by weight compared with
glycoproteins)
• Mucins or mucoproteins are, like
proteoglycans, predominantly carbohydrates
• Carbohydrates bind to the protein via:
– O-glycosidic linkage (through a residue of serine, threonine or
hydroxylysine and galactose or the disaccharide, glucosyl-
galactose). The linkage with 5-hydroxylysine is generally met in
collagen.
– N-glycosidic linkage, to the amide group of an asparagine
residue and N-AcGlu - N-AcGlu -mannose; it is prevalent in
mammalian glycoproteins.

O-glycosidic linkage N-glycosidic linkage

O-glycosidic linkage
– O-glycosidic bond
between a xylose residue
(Xyl) and a serine one in
protein. Two other residues
of galactose (Gal) are
attached to Xyl, forming a
three-saccharide bridge
Gal-Gal-Xyl-Ser. Then
follows the rest of the sugar
chain.
– O-glycosidic bond between
N-acetylgalactose- (N-
AcGal) and serine or
threonine in the protein.
• N-glycosidic linkage

β-L-fucose

acid sialic : N-acetyl neuraminic acid

• Glcosylation takes place in the lumen of the
endoplasmic reticulum (ER) and in the Golgi complex
(with important role in protein trafficking)
• N-linked glycosylation begins in the ER and continue in
the Golgi
• O-linked glycosylation exclusivelly takes place in the
Golgi
• Carbohydrates units
are altered and
elaborated in the
Golgi complex (stack
of flattened
membranous sacs)
• The Golgi complex is
the major sorting
center of the cell.
O A B
Blood groups are based on glycosylation patterns by the
glycosyltransferase enzyme
 Glycosilation (glycation)
• Glucose reacts directly with amino function of proteins, inducing
their glycation
• glycation of haemoglobin to the N-terminal valine residue of the β-
globin ⇒ glycated haemoglobin A1c.
• used in following dosing of patients with diabetes mellitus because it
reflects the level of glucose (glycemia) 3 weeks before the
determination of glucose