BIOC1600

Perspectives in
Biochemistry
Carbohydrates
BONNY YUEN, PH.D.

SCHOOL OF BIOMEDICAL
SCIENCES
biochemistry3rst.wordpress.com
FA C U LT Y O F M E D I C I N E , H K U
Handout overview
Classification of carbohydrates
Monosaccharides, disaccharides → polysaccharides
Glycosidic bond
Functions of carbohydrates
◦ Fuel sources
◦ Structural component
◦ Cell signaling

2
Elements important for living organisms
Red: common elements in living tissues
Blue: less common elements in living
tissues
Green: trace elements in living tissues
Grey: elements not found in living tissues

C, H, O all in Red:
Carbohydrate is extremely common and
important in living organisms

Typical structure of a
carbohydrate

3
Carbohydrates = [Carbon] + [hydrates]
Typically produced from CO2 and H2O via photosynthesis in plants.
carbohydrates = aldehydes or ketones with at least two hydroxyl groups, or substances that yield
such compounds on hydrolysis
Typically have the chemical formula (CH2O)n
Size
◦ glyceraldehyde (Mw = 90 g/mol)
◦ amylopectin (Mw = 200,000,000 g/mol)

Can be covalently linked with proteins to form glycoproteins.

4
Basic biological functions include:
Energy source & energy storage
RNA / DNA (ribose & deoxyribose)
Structural component of cell walls (plants) & exoskeletons (arthropods)
Informational molecules in cell-cell signaling (in the form of glycoproteins)

5
Chitin and chitosan sources and reported
uses

Jardine& Sayed (2017). Pure and Applied Chemistry. 90. 10.1515/pac-2017-0707.

6
Classification of carbohydrates
monosaccharides = simple sugars, consist of a single polyhydroxy aldehyde or ketone unit
◦ example: D-glucose

disaccharides = oligosaccharides with two monosaccharide units

◦ example: sucrose (D-glucose and D-fructose)

oligosaccharides = short chains of monosaccharide units, or residues, joined by glycosidic bonds

polysaccharides = sugar polymers with 10+ monosaccharide units
◦ examples: cellulose (linear), glycogen (branched)

7
Question 1
A(n) ________ is a(n) ________ with two monosaccharide units.

A. oligosaccharide; polysaccharide
B. polysaccharide; oligosaccharide
C. disaccharide; oligosaccharide
D. disaccharide; polysaccharide
Principle 1 – Stereoisomerism in Sugars
Carbohydrates can have multiple chiral carbons; the configuration of groups around each
carbon atom determines how the compound interacts with other biomolecules.
◦ As we saw for L-amino acids in proteins, with rare exceptions, biological evolution selected one
stereochemical series (D-series) for sugars.

sugar stereoisomers arise because many of the carbon atoms to which the hydroxyl groups are
attached are chiral centers

enzymes that act on sugars are stereospecific

 Two Families of Monosaccharides Are
Aldoses and Ketoses
backbones of monosaccharides:
◦ unbranched carbon chains with single bonds linking all carbon atoms
◦ one of the carbon atoms is double-bonded to an oxygen atom to form a carbonyl group
◦ other carbon atoms are bonded to a hydroxyl group

aldose
• carbonyl group is at
an end of the carbon
chain (in an aldehyde
group)
ketose
• carbonyl group is at
any other position (in
a ketone group)

10
Question
What chemical feature determines if a sugar is an aldose or a ketose?

A. the direction of rotation of polarized light

B. the position of the carbonyl carbon
C. if the enantiomers resemble either glyceraldehyde or dihydroxyacetone
D. if the epimers differ in configuration around one carbon or more than one carbon

11
Question
Glucose is a monosaccharide with a(n):

A. aldehyde functional group and six carbons.

B. ketone functional group and six carbons.
C. aldehyde functional group and seven carbons.
D. ketone functional group and seven carbons.

12
 What Makes Sugar Sweet?
TAS1R2 and TAS1R3 encode sweet-taste
receptors
binding of a compatible molecule
generates a “sweet” electrical signal in the
brain
◦ Stereoisomerism really matters!

sweetness
bitterness

13
Monosaccharides Have
Asymmetric Centers
all monosaccharides (except dihydroxyacetone) contain 1+ chiral
carbon atom
◦ occur in optically active isomeric forms

enantiomers = two different optical isomers that are mirror images

◦ a molecule with n chiral centers can have 2n stereoisomers

D isomers
• configuration at reference carbon is the same as D-glyceraldehyde
on the right (dextro) in a projection formula
• most hexoses of living organisms
L isomers
• configuration at reference carbon is the same as L-glyceraldehyde
• on the left (levo) in a projection formula

14
D-Aldoses (for your information only)

• C atoms in red = chiral centers

• The chiral C most distant from
the C=O has the same
configuration as the chiral carbon
in D=glyceraldehye.

15
D-Ketoses
(for your information only)

16
Epimers
epimers = two sugars that differ only in the configuration around one carbon atom

17
Formation of the Two Cyclic Forms of D-
Glucose
reaction between the aldehyde group at C-1 and the
hydroxyl group at C-5 forms a hemiacetal linkage
mutarotation = the interconversion of α and β anomers

◦ anomers = isomeric forms of monosaccharides that differ

only in their configuration about the hemiacetal or
hemiketal carbon atom

anomeric carbon = the carbonyl carbon atom

18
 Haworth Projection Formulas
Cyclic sugar structures are more accurately
depicted using “Haworth” projections. The six
carbon sugar ring is tilted to make the plane almost
perpendicular to the paper, with the bonds closest
drawn thicker than the bonds further away.

pyranoses = six-membered ring compounds (5C, one O)

furanoses = five-membered ring compounds (4C, one O)

19
Question
Using the Fischer projection of D-glucose, identify which statement is true of the Haworth
perspective formula of α-D-glucopyranose.

A. The terminal —CH2OH group projects downward.

B. The anomeric hydroxyl is on the opposite side from C-6.
C. The hydroxyl group on C-2 is placed pointing up.
D. The cyclic structure is a five-membered ring.

20
O-Glycosidic Bonds
O-glycosidic bond = covalent linkage joining two
monosaccharides
◦ formed when a hydroxyl group of one sugar
molecule (b-D-glucose) reacts with the anomeric
carbon of the other (a-D-glucose)
◦ readily hydrolyzed by acid

21
The Reducing End
formation of a glycosidic bond renders a sugar
nonreducing
reducing end = the end of a disaccharide or
polysaccharide chain with a free anomeric
carbon

Free anomeric carbon

22
What is a reducing sugar?
Benedict’s test Carbonyl → carboxyl

Reducing sugar test is the basis of blood sugar meters!

23
24
Three Common
Disaccharides
lactose is a reducing disaccharide

sucrose and trehalose are nonreducing sugars

◦ NO free hemiacetal group

anomeric carbon = the carbonyl carbon atom

25
 The Role of Lactase and Lactose
Intolerance

A proportion of the human

population possess a mutation
that maintains lactase
production in adulthood

https://ib.bioninja.com.au/standard-level/topic-2-molecular-biology/25-enzymes/lactose-intolerance.html 26
Polysaccharides
Principle 2:

Monomeric subunits, monosaccharides, serve as the building blocks of large carbohydrate

polymers.
◦
◦ The specific sugar, the way the units are linked, and whether the polymer is branched determine its
properties and thus its function.

27
Polysaccharides
most carbohydrates in nature occur as polysaccharides
(Mr > 20,000)
i.e., glycans

homopolysaccharides = contain only a single monomeric

sugar species
◦ serve as storage forms and structural elements

heteropolysaccharides = contain 2+ kinds of monomers

◦ provide extracellular support

28
Question
Which statement is false regarding homopolysaccharides and heteropolysaccharides?

A. Homopolysaccharides contain a single monomeric sugar species.

B. Some homopolysaccharides serve as structural elements in animal exoskeletons.
C. Heteropolysaccharides serve as storage forms of monosaccharides that are used as fuel.
D. In animal tissues, the extracellular space is occupied by several types of
heteropolysaccharides.

29
Principle 3
The sequences of complex polysaccharides are determined by the intrinsic properties
of the biosynthetic enzymes that add each monomeric unit to the growing polymer.

◦ This is in contrast with DNA, RNA, and proteins, which are synthesized on templates that direct their
sequence.

◦ ➔ Polysaccharides generally do not have defined lengths or molecular weights

30
Homopolysaccharides Are Storage Forms
of Fuel
storage polysaccharides
◦ Plant cells – starch
◦ amylose = long, unbranched chains of D-glucose residues connected by (α1→4) linkages
◦ amylopectin = larger than amylose with (α1→4) linkages between glucose residues and highly branched due to (α1→6) linkages
◦ Animal cells – glycogen
◦ polymer of (α1→4)-linked glucose subunits, with (α1→6)-linked branches
◦ more extensively branched
◦ more compact than starch

starch and glycogen molecules are heavily hydrated

◦ because they have many exposed hydroxyl groups available to hydrogen bond

31
 a-1,6-glycosidic bond
Glycosidic bonds
a-1,4-glycosidic bond

32
Polysaccharides assume three-
dimensional structures with the
lowest-energy conformations,
determined by covalent bonds,
hydrogen bonds, charge
interactions, and steric factors.
33
Question
What O-glycosidic bond is commonly found in amylose, amylopectin, and glycogen?

A. (β14)
B. (α16)
C. (β16)
D. (α14)

34
 For your information only

By Mark Cidade - Own work, CC BY-SA 4.0,

https://commons.wikimedia.org/w/index.php?curid=41182960
35
Peptidoglycan Reinforces the Bacterial
Cell Wall
peptidoglycan = rigid component of bacterial cell walls
◦ heteropolymer of alternating (β1→4)-linked N-acetylglucosamine and N-acetylmuramic acid residues
◦ cross-linked by short peptides

36
Glycosaminoglycans – Heteropolysaccharides
of the Extracellular Matrix
extracellular matrix (ECM) = gel-like material in the
extracellular space of tissues that holds cells together and
provides a porous pathway for nutrient and O2 diffusion
◦ composed of an interlocking meshwork of
heteropolysaccharides (ground substance) and fibrous proteins

basement membrane (specialized ECM) also contains

heteropolysaccharides

Glycosaminoglycans provide viscosity, adhesiveness, and

tensile strength to the extracellular matrix

37
Structures and Roles of Some Polysaccharides
Polymer Type Repeating unit Size (number of Roles/significance
monosaccharide units)
Starch: Homo- (𝛼1→4)Glc, 50-5,000 Energy storage: in plants
Amylose linear
Starch: Homo- (𝛼1→4)Glc, with Up to 106 Energy storage: in plants
Amylopectin (𝛼1→6)Glc
branches every
24-30 residues
Glycogen Homo- (𝛼1→4)Glc, with Up to 50,000 Energy storage: in bacteria and animal
(𝛼1→6)Glc cells
branches every
8-12 residues
Cellulose Homo- (𝛽1→4)Glc Up to 15,000 Structural: in plants, gives rigidity and
strength to cell walls
Chitin Homo- (𝛽1→4)GlcNAc Very large Structural: in insects, spiders,
crustaceans, gives rigidity and strength
to exoskeletons
Dextran Homo- (𝛼1→6)Glc, with Wide range Structural: in bacteria, extracellular
(𝛼1→3) adhesive
branches
Peptidoglycan Hetero-; peptides 4)Mur2Ac(𝛽1→4 Very large Structural: in bacteria, gives rigidity and
attached ) GlcNAc (𝛽1 strength to cell envelope
Hyaluronan (a glycosaminoglycan) Hetero-; acidic 4)GlcA(𝛽1→3) Up to 100,000 Structural: in vertebrates, extracellular
GlcNAc (𝛽1 matrix of skin and connective tissue;
38
viscosity and lubrication in joints
Principle 4
Molecular complementarity is central to function.
The recognition of oligosaccharides by sugar-binding proteins (lectins) results from a
perfect fit between lectin and ligand.

39
Glycoproteins
glycoproteins
◦ outer face of the plasma membrane, in ECM, in blood, and in organelles (Golgi complexes, secretory
granules, and lysosomes)
◦ oligosaccharide portions are heterogenous and rich in information

glycolipids
glycosphingolipids = class of glycolipids
◦ Rich in neurons
◦ signal transduction

40
Purpose of Interactions between Cells
and the ECM
interactions between cells and the ECM:
◦ anchor cells to the ECM, providing the strength and elasticity of skin and joints
◦ provide paths that direct the migration of cells in developing tissue
◦ convey information in both directions across the plasma membrane

41
 Attachment of oligosaccharides
to glycoprotein
two types of attachments:

◦ O-linked = a glycoside bond joins the

anomeric carbon of a carbohydrate
to the —OH of a Ser or Thr residue

◦ N-linked = an N-glycosyl bond joins

the anomeric carbon of a sugar to
the amide nitrogen of an Asn residue

Asn = Asparagine
Ser = Serine
Thr = Threonine

42
Other examples of Glycoproteins
mucins = secreted or membrane glycoproteins
◦ large numbers of O-linked oligosaccharide chains
◦ in most secretions

proteins of the blood

◦ immunoglobulins (antibodies), follicle-stimulating hormone, luteinizing hormone, and thyroid-
stimulating hormone

milk proteins
◦ major whey protein α-lactalbumin

43
For your information only

Štambuk et al. (2020). Molecular Aspects of Medicine. 79. 100891. 10.1016/j.mam.2020.100891.

44
The Biological Advantages of Adding
Oligosaccharides to Proteins
covalently attached oligosaccharides:
◦ influence the folding and stability of the proteins
◦ provide critical information about the targeting of newly synthesized proteins
◦ allow specific recognition by other proteins

45
 Role of Lectin-Ligand Interactions in Leukocyte Movement

lectins
- bind carbohydrates with
high specificity and with
moderate to high affinity

Selectins
- family of plasma
membrane lectins
- Transplanted organs
rejection

A leukocyte circulating through a capillary is slowed by transient interactions between P-selectin molecules in the plasma membrane of the
capillary endothelial cells and glycoprotein ligands for P-selectin on the leukocyte surface. As the leukocyte interacts with successive P-selectin
molecules, it rolls along the capillary surface. Near a site of inflammation, stronger interactions between integrin in the leukocyte surface and its
ligand in the capillary surface lead to tight adhesion. The leukocyte stops rolling and, under the influence of signals from the site of
inflammation, escapes through the capillary wall as it moves toward the region of inflammation.
46
Role of oligosaccharides in recognition events at
the cell surface and in the endomembrane system.
(a) Oligosaccharides with unique structures (represented
as strings of red hexagons) are components of a
variety of glycoproteins or glycolipids on the outer
surface of plasma membranes. Their oligosaccharide
moieties are bound by extracellular lectins with high
specificity and affinity.
(b) Viruses that infect animal cells, e.g., influenza virus,
bind to cell surface glycoproteins as the first step in
infection.
(c) Bacterial toxins, e.g., cholera, bind to a surface
glycolipid before entering a cell.
(d) Some bacteria, e.g., H. pylori, adhere to and then
colonize or infect animal cells.
(e) Selectins (lectins) in the plasma membrane of certain
cells mediate cell-cell interactions, such as those of
leukocytes with the endothelial cells of the capillary
wall at an infection site.
(f) The mannose 6-phosphate receptor/lectin of the trans
Golgi complex binds to the oligosaccharide of
lysosomal enzymes, targeting them for transfer into
the lysosome.
47
Glycoprotein and blood types

48
Summary
Classification and nomenclature of monosaccharides and disaccharides
Different types of polysaccharides
◦ Structure
◦ Roles and functions (fuel? Structural role?)

Glycoconjugates
◦ Peptidoglycans
◦ Glycoproteins
◦ Glycolipids

Carbohydrates as informational molecules

49
References
Nelson, D. and Cox, M. (2021). Chapter 7 Carbohydrates and Glycobiology. In Lehninger
Principles of Biochemistry, 8th ed. W H Freeman & Co.
https://alevelbiology.co.uk/notes/polysaccharides/ (accessed on 19 Sept 2022)

50