carbohydrate

1. Presented by
Dr. A. K. M. Arif Uddin Ahmed.
Lecturer, Department of Pharmacology & Biochemistry.
Medical College of Xiamen University, China
Section II (A)
Biochemistry
Carbohydrate
1

2. Carbohydrate
2

3. CARBOHYDRATES ARE ALDEHYDE OR KETONE
DERIVATIVES OF POLYHYDRIC ALCOHOLS.
They are the end products of photosynthesis.
Contain three elements - C, H, O,
According to the formula (CH2O)n where n ≥ 3.
Example:-
3

4. Plants:
photosynthesis
chlorophyll
6 CO2 + 6 H2O C6H12O6 + 6 O2
sunlight (+)-glucose
(+)-glucose starch or cellulose
respiration
C6H12O6 + 6 O2 6 CO2 + 6 H2O + energy
Animals
plant starch (+)-glucose
(+)-glucose glycogen
glycogen (+)-glucose
(+)-glucose fats or aminoacids
respiration
(+)-glucose + 6 O2 6 CO2 + 6 H2O + energy
4

5. Functions of carbohydrate
•Carbohydrates are essential to all living
organisms and are the most abundant class of
biological molecules.
•The metabolic breakdown of monosaccharides
provides most of the energy used to power
biological processes.
•In structural material (cell walls, connective
tissue)
•Important for cell signalling, cell-cell interactions
5

6. Classification of carbohydrates
• Monosaccharides- glucose, fructose
• Oligosaccharides
• Disaccharides, trisaccharides, tetrasaccharides,
pentasaccharides, hexasaccharides, (up to 10
monosaccharides )
• Most important are the disaccharides- maltose,
lactose, sucrose .
• Polysaccharides
• Homopolysaccharides- starch, glycogen, cellulose,
chitin, inulin.
• Heteropolysaccharides
• Complex carbohydrates
6

7. Monosaccharides
The monosaccharide commonly found in humans are
classified according to the number of carbons they contain in
their backbone structures.
Classifications of monosaccharide
Trioses (C3
H6
O3
) Glyceraldehyde Dihydroxyacetone
Tetroses (C4
H8
O4
) Erythrose Erythrulose
Pentoses (C5
H10
O5
) Ribose Ribulose
Hexoses (C6
H12
O6
) Glucose Fructose
Heptoses (C7
H14
O7
) — Sedoheptulose
ALDOSES KETOSES
7

8. Aldoses
Aldoses are monosaccharides
• with an aldehyde group
• with many hydroxyl (-OH)
groups.
triose (3C atoms)
tetrose (4C atoms)
pentose (5 C atoms)
hexose (6 C atoms)
O
║
C─H aldose
│
H─ C─OH
│
H─ C─OH
│
CH2OH
Erythose, an aldotetrose
8

9. Ketoses
Ketoses are monosaccharides
• with a ketone group
• with many hydroxyl (-OH)
groups.
CH2OH
│
C=O ketose
│
H─ C─OH
│
H─ C─OH
│
H─C─OH
│
CH2OH
Fructose, a ketohexose
9

10. Identify each as aldo- or keto- and as tetrose, pentose,
or hexose:
H
CH2OH
OHC
H
H
H
OH
OH
OH
C
C
C
HC
O
CH2OH
HHO
CH2OH
O
H OHC
C
C
aldohexose
ketopentose
10

11. Trioses
(C3
H6
O3
)
Tetroses
(C4
H8
O4
)
11

12. Pentoses
(C5
H10
O5
)
Hexoses
(C6
H12
O6
)
12

13. Epimers
(two sugars that differ only in the configuration around one carbon atom)
13

14. Monosaccharides have asymmetric centers
Three ways to represent the two stereoisomers of glyceraldehyde
14

15. 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
15

16. Formation of hemiacetals and hemiketals
16

17. Cyclic Structures
Cyclic structures
• are the prevalent form of monosaccharides with 5 or 6 carbon
atoms.
• form when the hydroxyl group on C-5 reacts with the
aldehyde group or ketone group.
O O
17

18. The Formation of Cyclic Glucose
18

19. Alpha, Beta anomers
The α and β anomes of D-glucose
interconvert in aqueous solution
by a process called mutarotation.
Isomeric forms of monosaccharides that
differ only in the configuration of the
number-1 carbon atom are called
anomers.
19

20. Cyclic Structure of Fructose
Fructose
• is a ketohexose.
• forms a cyclic structure.
• reacts the —OH on C-5 with the C=O on C-2.
D-fructose β-D-fructoseα-D-fructose
O CH2OH
OH
OH
OH
CH2OH
O OH
CH2OH
OH
OH
CH2OH
H OH
H OH
HHO
O
CH2OH
C
C
C
C
CH2OH
20

21. Pyranoses
and
furanoses
21

22. Conformational
formulas of
pyranoses
22

23. Some hexose derivatives important in biology
23

24. Reducing Sugars
• Sugars that contain aldehyde groups that are oxidized
to carboxylic acids are classified as reducing sugars.
• Common test reagents are :
• Benedicts reagent (CuSO4
/ citrate)
• Fehlings reagent (CuSO4
/ tartrate)
• They are classified as reducing sugars since they
reduce the Cu2+
to Cu+
which forms as a red precipitate,
copper (I) oxide.
24

25. Glucose and other sugars capable of reducing Cu2+
are called reducing sugars.
Sucrose is non reducing sugar.
25
Reducing Sugars

26. Physiologic Importance of Pentoses.
Sugar Source Biochemical and Clinical
Importance
D-Ribose Nucleic acids and
metabolic intermediate
Structural component of
nucleic acids and coenzymes,
including ATP, NAD(P), and
flavin coenzymes
D-Ribulose Metabolic intermediate Intermediate in the pentose
phosphate pathway
D-Arabinose Plant gums Constituent of glycoproteins
D-Xylose Plant gums,
proteoglycans,
glycosaminoglycans
Constituent of glycoproteins
L-Xylulose Metabolic intermediate Excreted in the urine in
essential pentosuria
26

27. Physiologic Importance of Hexoses.
Sugar Source Biochemical Importance Clinical Significance
D-Glucose Fruit juices, hydrolysis of
starch, cane or beet sugar,
maltose and lactose
The main metabolic fuel for
tissues; "blood sugar"
Excreted in the urine
(glucosuria) in poorly
controlled diabetes
mellitus as a result of
hyperglycemia
D-Fructose Fruit juices, honey,
hydrolysis of cane or beet
sugar and inulin, enzymic
isomerization
of glucosesyrups for food
manufacture
Readily metabolized either
via glucoseor directly
Hereditary fructose
intolerance leads to
fructose accumulation
and hypoglycemia
D-Galactose Hydrolysis of lactose Readily metabolized to glucose;
synthesized in the mammary
gland for synthesis of lactose in
milk. A constituent of
glycolipids and glycoproteins
Hereditary galactosemia
as a result of failure to
metabolize galactose
leads to cataracts
D-Mannose Hydrolysis of plant
mannan gums
Constituent of glycoproteins
27

28. Oligosaccharide
Some common Disaccharides:
Maltose, a cleavage product of starch (e.g., amylose), is a
disaccharide with an α(1→ 4) glycosidic link between C1 - C4
OH of 2 glucoses. It is the α anomer (C1 O points down).
Lactose, milk sugar, is composed of galactose & glucose,
with β(1→4) linkage from the anomeric OH of galactose. Its
full name is β-D-galactopyranosyl-(1→ 4)-α-D-glucopyranose
Sucrose, common table sugar, has a glycosidic bond linking
the anomeric hydroxyls of glucose & fructose.Because the
configuration at the anomeric C of glucose is α (O points
down from ring), the linkage is α(1→2). The full name of
sucrose is α-D-glucopyranosyl-(1→2)-β-D-fructopyranose.) 28

29. Important Disaccharides
A disaccharide consists of two monosaccharides.
Monosaccharides Disaccharide
glucose + glucose maltose + H2O
glucose + galactose lactose + H2O
glucose + fructose sucrose + H2O
29

30. Disaccharides contain a glycosidic bond
Formation
of
maltose
anomeric carbon
Glu(α1→4)Glu
The glycosidic bond protects the
anomeric carbon from oxidation.
30

31. Some common disaccharides
reducing sugar
non reducing sugar
reducing sugar
31

32. Maltose
Maltose is
• a disaccharide also known as malt sugar.
• composed of two D-glucose molecules.
• obtained from the hydrolysis of starch.
• used in cereals, candies, and brewing.
• found in both the α- and β - forms.
32

33. Formation of Maltose
Free α-OH
33

34. Lactose
Lactose
• is a disaccharide of β-D-
galactose and α- or β-D-
glucose.
• contains a β -1,4-
glycosidic bond.
• is found in milk and milk
products.
α-
form
α-
form
34

35. Sucrose
Sucrose or table sugar
• is obtained from sugar cane and sugar beets.
• consists of α-D-glucose and β-D-fructose..
• has an α,β-1,2-glycosidic bond.
α-D-glucose
β -D-fructose
35

36. Sweetness of Sweeteners
Sugars and artificial
sweeteners
• differ in
sweetness.
• are compared to
sucrose (table
sugar), which is
assigned a value of
100. 60 000
36

37. Learning Check
Identify the monosaccharides in each of the following:
A. lactose
(1) α-D-glucose (2) β-D-fructose (3) β-D-galactose
B. maltose
(1) α-D-glucose (2) β-D-fructose (3) β-D-galactose
C. sucrose
(1) α-D-glucose (2) β-D-fructose (3) β-D-galactose
37

38. Sugar Source Clinical Significance
Isomaltose Enzymic hydrolysis of starch
(the branch points in
amylopectin)
Maltose Enzymic hydrolysis of starch
(amylase); germinating cereals
and malt
Lactose Milk (and many pharmaceutical
preparations as a filler)
Lack of lactase (alactasia) leads to
lactose intolerance—diarrhea and
flatulence; may be excreted in the urine
in pregnancy
Lactulose Heated milk (small amounts),
mainly synthetic
Not hydrolyzed by intestinal enzymes,
but fermented by intestinal bacteria;
used as a mild osmotic laxative
Sucrose Cane and beet sugar, sorghum
and some fruits and vegetables
Rare genetic lack of sucrase leads to
sucrose intolerance—diarrhea and
flatulence
Trehalose Yeasts and fungi; the main sugar
of insect hemolymph
Physiologic Importance of Disaccharides.
38

39. Polysaccharides
• Homopolysaccharides:- (starch, glycogen, cellulose,
Chitin, inulin)
• Heteropolysaccharides:- (peptidoglycan, agarose,
hyaluronate, chondroitin sulfate, keratan sulfate,
heparin)
• Characteristics of polysaccharides:
• polymers (MW from 200,000)
• White and amorphous products (glassy)
• not sweet
• not reducing; do not give the typical aldose or ketose reactions)
• form colloidal solutions or suspensions
39

40. Polysaccharides
(also called Glycans)
Most carbohydrates
found in nature occur
as polysaccharides.
40

41. Starch
• most common storage polysaccharide in
plants
• composed of 10 – 30% α−amylose and 70-
90% amylopectin depending on the source
• Common sources are grains , potatoes, peas,
beans, wheat
41

42. Electron micrographs of starch granules
42

43. Amylose and amylopectin, the polysaccharides of starch
amylopectin
occurs every
24 to 30 residues
Strands of amylopectin form double helical
structures with each other or with amylose strands
43

44. Structures of Amylose and
Amylopectin
44

45. Amylose
Amylose is
• a polymer of α-D-
glucose molecules.
• linked by α-1,4
glycosidic bonds.
• a continuous
(unbranched) chain.
45

46. Amylopectin
Amylopectin
• is a polymer of α-D-
glucose molecules.
• is a branched-chain
polysaccharide.
• has α-1,4-glycosidic
bonds between the
glucose units.
• has α-1,6 bonds to
branches.
46

47. Dextrins
• Starches like amylose and amylopectin
hydrolyze to dextrins (smaller
polysaccharides)
• Contain 3-8 glucose units
47

48. Glycogen
• also known as animal starch
• stored in muscle and liver
• present in cells as granules (high MW)
• contains both α(1,4) links and α(1,6) branches at
every 8 to 12 glucose unit
• complete hydrolysis yields glucose
48

49. Electron micrographs of glycogen
49

50. Glycogen, the glucose storage polymer in animals, is similar in
structure to amylopectin.
But glycogen has more α(1→6) branches.
The highly branched structure permits rapid glucose release from
glycogen stores, e.g., in muscle during exercise.
The ability to rapidly mobilize glucose is more essential to animals
than to plants.
H O
OH
H
OHH
OH
CH2OH
H
O H
H
OHH
OH
CH2OH
H
O
HH H O
O
H
OHH
OH
CH2
H
H H O
H
OHH
OH
CH2OH
H
OH
HH O
O
H
OHH
OH
CH2OH
H
O
H
O
1 4
6
H O
H
OHH
OH
CH2OH
H
H H O
H
OHH
OH
CH2OH
H
H
O
1
OH
3
4
5
2
glycogen
Glycogen
50

51. Glycogen Molecule
B branched
G
A
AA
A
A
A
A
A
B
C
B BB
B
B
B
B
A linear
50 000 glucose units
2 000 non-reducing ends
All chains of same length
(11~15 Glucose/chain)
2 branching points/B chain
51

52. Cellulose, a major constituent of plant cell walls, consists
of long linear chains of glucose with β(1→4) linkages.
Every other glucose is flipped over, due to β linkages.
This promotes intra-chain and inter-chain H-bonds and
van der Waals interactions, that cause cellulose chains to
be straight & rigid.
cannot be digested by humans because humans cannot
break down - β(1→4) glycosidic bonds.
cellulose
H O
OH
H
OHH
OH
CH2OH
H
O
H
OHH
OH
CH2OH
H
O
H H O
O H
OHH
OH
CH2OH
H
H O
H
OHH
OH
CH2OH
H
H
OHH O
O H
OHH
OH
CH2OH
H
O
H H H H
1
6
5
4
3
1
2
Cellulose
52

53. Chitin – exoskeleton of anthropods.
Linear, unbranched homopolymer.
N-acetylglucosamine units in (β1→4)
linkage.
Only difference from cellulose is the
acetylated amino group instead of –
OH at C-2.
Chitin
53

54. Functions of homopolysaccharides
Starch
homopolymer, called a glucosan or glucan. most important dietary source of
carbohydrate. constituents are amylose (13–20%), nonbranching helical structure,
and amylopectin (80–85%),
Glycogen
storage polysaccharide. D-glucopyranose residues (in 1 4 glucosidic linkage) with
branching by means of 1 6 glucosidic bonds .
Dextrins
are intermediates in the hydrolysis of starch.
Cellulose
insoluble -D-glucopyranose 1 4 bonds cross-linking hydrogen bonds.
Chitin
exoskeleton of crustaceans and insects.
Inulin
polysaccharide of fructose ,used to determine the glomerular filtration rate,
54

55. Peptidoglycan of Bacterial cell walls
Alternating (β1→4) linked GlcNAc and Mur2Ac residues.
Lysozyme in tears and saliva cleaves the linkage.
Penicillin and β-lactamase
Heteropolysaccharides
55

56. Used in Agarose gel electrophoresis & nucleic acids separation
Agarose in seaweeds (Algae)
Heteropolysaccharides
56

57. Repeating units of some common glycosaminoglycans of extracellular matrix
linear polymers composed of
repeating disaccharide units
Glucoronic acid
N-Acetylglucosamine
Heteropolysaccharides
57

58. Glycosaminoglycans (mucopolysaccharides) are linear
polymers of repeating disaccharides.
The constituent monosaccharides tend to be modified,
with acidic groups, amino groups, sulfated hydroxyl and
amino groups, etc.
Glycosaminoglycans tend to be negatively charged,
because of the prevalence of acidic groups.
H O
H
H
OHH
OH
COO−
H
H O
OH H
H
NHCOCH3H
CH2OH
H
OO
D-glucuronate
O
1
23
4
5
6
1
23
4
5
6
N-acetyl-D-glucosamine
hyaluronate
58

59. Hyaluronate (hyaluronan) is a glycosaminoglycan with a
repeating disaccharide consisting of 2 glucose derivatives,
glucuronate (glucuronic acid) & N-acetyl-glucosamine.
The glycosidic linkages are β(1→3) & β(1→4).
H O
H
H
OHH
OH
COO−
H
H O
OH H
H
NHCOCH3H
CH2OH
H
OO
D-glucuronate
O
1
23
4
5
6
1
23
4
5
6
N-acetyl-D-glucosamine
hyaluronate
59

60. Heparin or Heparan sulfate is initially synthesized on a
membrane-embedded core protein as a polymer of alternating
N-acetylglucosamine and glucuronate residues.
Later, in segments of the polymer, glucuronate residues may be
converted to the sulfated sugar iduronic acid, while
N-acetylglucosamine residues may be deacetylated and/or
sulfated.
H O
H
OSO3
−
H
OH
H
COO−
O H
H
NHSO3
−
H
OH
CH2OSO3
−
H
H
H
O
O
heparin or heparan sulfate - examples of residues
iduronate-2-sulfate N-sulfo-glucosamine-6-sulfate
60

61. Heparin, a soluble glycosaminoglycan found
in granules of mast cells, has a structure
similar to that of heparan sulfates, but is
more highly sulfated.
When released into the blood, it inhibits clot
formation by interacting with the protein
antithrombin.
Heparin has an extended helical
conformation.
heparin: (IDS-SGN)5
PDB 1RID
C O N S
Charge repulsion by the many negatively charged groups may contribute
to this conformation.
Heparin shown has 10 residues, alternating IDS (iduronate-2-sulfate) &
SGN (N-sulfo-glucosamine-6-sulfate).
61

62. 62

63. Glycoconjugates (Proteoglycans, Glycoproteins,
Glycolipids)
Glycoconjugate: Biologically active molecule made from a
carbohydrate covalently linked to a protein or lipid
(glycoprotein or glycolipid) -- found at cell surfaces
Both glycoproteins and glycolipids are important in:
Cell-cell recognition and adhesion,
Cell migration during development
Blood clotting, The immune response, Wound healing, etc.
In all these cases, the carbohydrate parts serve as the
information carrier by providing specific, high affinity
recognition sites.
Complex carbohydrates
63

64. Some proteoglycans of the extracellular matrix bind non-
covalently to hyaluronate via protein domains called link modules.
E.g.:
• Multiple copies of the aggrecan proteoglycan associate with
hyaluronate in cartilage to form large complexes.
• Versican, another proteoglycan, binds hyaluronate in the
extracellular matrix of loose connective tissues.
H O
H
H
OHH
OH
COO−
H
H O
OH H
H
NHCOCH3H
CH2OH
H
OO
D-glucuronate
O
1
23
4
5
6
1
23
4
5
6
N-acetyl-D-glucosamine
hyaluronate
Proteoglycans
64

65.  The core protein of a syndecan heparan sulfate
proteoglycan includes a single transmembrane α-helix,
as in the simplified diagram above.
 The core protein of a glypican heparan sulfate
proteoglycan is attached to the outer surface of the
plasma membrane via covalent linkage to a modified
phosphatidylinositol lipid.
heparan sulfate
glycosaminoglycan
cytosol
core
protein
transmembrane
α-helix
Some cell surface
heparan sulfate
glycosaminoglycans
remain covalently linked to
core proteins embedded in
the plasma membrane.
Proteoglycans
65

66. - (Smaller and diverse) carbohydrate (1~70% by mass)-protein
conjugates.
- Glycoproteins are found on the outer surface of plasma membrane,
in the extracellular matrix, in the blood, and in specific organelles,
Golgi complexes, lysosomes, and secretory granules.
• Why glycoproteins? – The biological advantages of adding
oligosaccharides to proteins:
- Increase polarity and solubility of the proteins.
- May influence the folding process.
- Protect from proteolytic enzymes.
- Responsible for specific biological activities:
Intracellular targeting of proteins
Cell-cell interactions, Tissue development
Extracellular signaling
-Carbohydrate forms a glycosidic linkage with the – OH of Ser or Thr
through its anomeric end (O-linked), or an N-glycosyl link through
the amide of Asn (N-linked).
Glycoproteins
66

67. Glycoproteins
67

68. O-linked oligosaccharide chains of glycoproteins vary in
complexity.
They link to a protein via a glycosidic bond between a sugar
residue & a serine or threonine OH.
O-linked oligosaccharides have roles in recognition, interaction,
and enzyme regulation.
Glycoproteins
68

69. N-acetylglucosamine (GlcNAc) is a common O-linked glycosylation of
protein serine or threonine residues.
Many cellular proteins, including enzymes & transcription factors, are
regulated by reversible GlcNAc attachment.
Often attachment of GlcNAc to a protein OH alternates with
phosphorylation, with these 2 modifications having opposite regulatory
effects (stimulation or inhibition).
Glycoproteins
69

70. N-linked oligosaccharides of glycoproteins tend to be complex
and branched.
First N-acetylglucosamine is linked to a protein via the side-chain
N of an asparagine residue in a particular 3-amino acid
sequence.
H O
OH
HN
H
H
HNH
OH
CH2OH
H
C CH3
O
C CH2 CH
O HN
C
HN
O
HC
C
HN
HC
R
O
C
R
O
Asn
X
Ser or Thr
N-acetylglucosamine
Initial sugar in N-linked
glycoprotein oligosaccharide
Glycoproteins
70

71. Additional monosaccharides are added, and the N-linked
oligosaccharide chain is modified by removal and addition of
residues, to yield a characteristic branched structure.
Glycoproteins
71

72. Many proteins secreted by cells have attached N-linked
oligosaccharide chains.
Genetic diseases have been attributed to deficiency of particular
enzymes involved in synthesizing or modifying oligosaccharide
chains of these glycoproteins.
Such diseases, and gene knockout studies in mice, have been used
to define pathways of modification of oligosaccharide chains of
glycoproteins and glycolipids.
Carbohydrate chains of plasma membrane glycoproteins and
glycolipids usually face the outside of the cell.
They have roles in cell-cell interaction and signaling, and in
forming a protective layer on the surface of some cells.
Glycoproteins
72

73. Lectinsare glycoproteins that recognize and bind to specific
oligosaccharides.
Concanavalin A & wheat germ agglutinin are plant lectins that have been
useful research tools.
Examples of animal lectins:
Mannan-binding lectin (MBL) is a glycoprotein found in blood plasma.
It binds cell surface carbohydrates of disease-causing microorganisms &
promotes phagocytosis of these organisms as part of the immune response.
Recognition/binding of CHO moieties of glycoproteins, glycolipids &
proteoglycans by animal lectins is a factor in:
• cell-cell recognition
• adhesion of cells to the extracellular matrix
• interaction of cells with chemokines and growth factors
• recognition of disease-causing microorganisms
• initiation and control of inflammation.
Glycoproteins
73

74. Glycolipids and Blood Group
- Blood group antigens are
immunochemical markers
made of glycolipids on the
surface of red blood cells.
- Those with type A cells have
type A antigens
on their cell surfaces, B have
B antigens, AB have both,
O carry the O antigen
- The only difference appears at
the terminal sugar
Glycolipids
74

75. Thank You
75