1. Macromolecules & Carbohydrates
Lecture 3
Dr. Mamoun Ahram

2. Cell's weight

3. Subunits
Subunits: the small building blocks (precursors) used to make macromolecules
Macromolecules: large molecules made of subunits

4. Macromolecules Carbohydrates (monosaccharides) Proteins (amino acids)
Nucleic acids (nucleotides)
Lipids (fatty acids)
Except for lipids, these macromolecules are also considered polymers

6. Relationship (monomers and polymers)

7. How water is removed?
Mechanism 1: One subunit contributes an “H” and the other subunit contributes an “OH”
Mechanism 2: One subunit contributes 2 “H” the other subunit contributes an “O”

8. Carbohydrates

9. Resource
This lecture
Campbell and Farrell’s Biochemistry, Chapter 16

10. What are they? Carbohydrates are polyhydroxy aldehydes or ketones
Saccharide is another name for a carbohydrate

11. Functions Source of energy Structure (cellulose and chitin)
Building blocks
Cellular recognition

12. Classification I By the number of sugars that constitute the molecule
Monosaccharides
Disaccharides
Oligosaccharides
Polysaccharides

13. Monosaccharides Basic chemical formula: (CH2O)n
They contain two or more hydroxyl groups

14. Drawing sugars Fisher projections or perspective structural formulas
Forward
Backward
Top (C1):
Most highly oxidized C

17. Numbering carbons…again

18. Numbering order of compounds with more than one functional group
Carboxylic acid
Aldehyde
Ketone
Alcohol
Amine
Alkyne = alkene
Alkane

19. Classification 2 By the number of carbon atoms they contain Triose
Tetrose
Pentose
Hexose
Heptose

22. Trioses

23. Glyceraldehyde
Chiral carbon

24. Constitutional isomers
Isomerism
Isomers
Stereoisomers
Enantiomers
L-isomers
D-isomers
Diastereomers
Non-epimers
Epimers
Constitutional isomers

25. Structural isomers
Same number of atoms, different connectivity

26. Stereoisomers
Same number of atoms and connectivity, but not superimposable

27. Number of possible stereoisomers
2n (n is the number of chiral carbons in a sugar molecule)

28. Isomers of glucose

29. Mirror images and non-superimposable, then…enantiomers

31. Light polarization

32. Sugar enantiomers (D- vs. L-)

33. Which one(s) is a chiral carbon?

34. Stereoisomers, but non-mirror images and non-superimposable, then…diastereomersOH H H OH

35. Diastereomers that differ in the orientation of one chiral carbon…epimers

36. Constitutional isomers
Isomerism
Isomers
Stereoisomers
Enantiomers
L-isomers
D-isomers
Diastereomers
Non-epimers
Epimers
Constitutional isomers

37. Formation of a ring structure

38. Ring structures

39. Example

40. Acetal/ketal vs. hemiacetal/hemiketal
Hemiacetal and hemiketal: ether and alcohol on same carbon
Acetal and ketal: two ethers on same carbon
What is the difference between hemiacetal and hemiketal and the difference between acetal and ketal?

41. Hemiacetal vs. hemiketal

42. Haworth vs. Fischer projections

43. Fischer vs. Haworth Left-right vs. up-down

44. Anomers

45. α vs β fructose

46. - vs. -glucopyranose

47. Cyclic fructose

48. Cyclic aldohexoses

49. Cyclic ribofuranose

50. Modified sugars

51. Sugar esters (esterification)
What is the reacting functional group? Where does it react? What are the end products? Where are they used?

52. Sugar acids (oxidation)
Where is it oxidized? What does it form?

53. Example 1

54. Example 2

55. Example 3

56. Note
Oxidation of ketoses to carboxylic acids does not occur, but they can be oxidized because of formation of enediol form

57. Benedict’s test

58. Sugar alcohols (reduction)
What does it form?
Examples include sorbitol, mannitol, and xylitol, which are used to sweeten food products

59. Deoxy sugars One or more hydroxyl groups are replaced by hydrogens
An example is 2-deoxyribose, which is a constituent of DNA

60. N-glycosides
What is the reacting functional group? Where does it react? What are the end products? Where are they used?
Examples: nucleotides (DNA and RNA)

61. Amino sugars
What is the reacting functional group? Where does it react? What are the end products? Where are they used?
Further modification by acetylation

62. O-Glycosides
What is the reacting functional group? Where does it react? What are the end products? Where are they used?

63. Formation of full acetal

64. Disaccharides
What are disaccharide? Oligosaccharides? Hetero- vs. homo-?
What is the type of reaction?
What is a residue?
Synthesizing enzymes are glycosyltransferases
Do they undergo mutarotation?
Are products stable?

65. Distinctions of disaccharides
The 2 specific sugar monomers involved and their stereoconfigurations (D- or L-)
The carbons involved in the linkage (C-1, C-2, C-4, or C-6)
The order of the two monomer units, if different (example: galactose followed by glucose)
The anomeric configuration of the OH group on carbon 1 of each residue (α or β)

66. Abundant disaccharides
Configuration
Designation
Naming (common vs. systematic)
Reducing vs. non-reducing

69. α vs β fructose

70. Sucrose

72. Raffinose What are oligosaccharide? Example: raffinose
It is found in peas and beans
Homework
What are the names of monosaccharides that make up raffinose?
What is the monosaccharide that is attached to what disaccharide?

73. Oligosaccharides as drugs
Streptomycin and erythromycin (antibiotics)
Doxorubicin (cancer chemotherapy)
Digoxin (cardiovascular disease)

74. Polysaccharides What are polysaccharides?
Homopolysaccharide (homoglycan) vs. heteropolysaccharides

75. Features of polysaccharides
Monosaccharides
Length
Branching

76. Storage polysaccharides
Glycogen
Starch
Dextran

77. Glycogen
Which organisms? Which organs?

78. Structure

79. Starch
Which organisms?
Forms:
amylase (10-20%)
amylopectin (80-90%)

80. Dextran A storage polysaccharide Yeast and bacteria
-(1-6)-D-glucose with branched chains
Branches: 1-2, 1-3, or 1-4

81. Structural polysaccharides

82. Cellulose
Which organism?
Degradation?

83. Structural features? Why?

84. Pectin
What is the precursor?
Where does it exist?

85. Chitin
What is the precursor?
Where does it exist?

86. Glycosaminoglycans What are they? Where are they located?
Derivatives of an amino sugar, either glucosamine or galactosamine
At least one of the sugars in the repeating unit has a negatively charged carboxylate or sulfate group

88. Localization and function of GAG
Comments
Hyaluronate
synovial fluid, vitreous humor, ECM of loose connective tissue
the lubricant fluid , shock absorbing
As many as 25,000 disaccharide units
Chondroitin sulfate
cartilage, bone, heart valves
most abundant GAG
Heparan sulfate
basement membranes, components of cell surfaces
contains higher acetylated glucosamine than heparin
Heparin
component of intracellular granules of mast cells lining the arteries of the lungs, liver and skin
A natural anticoagulant
Dermatan sulfate
skin, blood vessels, heart valves
Keratan sulfate
cornea, bone, cartilage aggregated with chondroitin sulfates
 Only one not having uronic acid

89. Bond orientation
Glycosidic bonds in chondroitin 4-sulfate, hyaluronate, dermatan sulfate, and keratan sulfate are alternating  (13) and (14) linkages
Exception is heparin

90. Proteoglycans Lubricants Structural components in connective tissue
Mediate adhesion of cells to the extracellular matrix
Bind factors that stimulate cell proliferation

91. Bacterial cell wall

92. Peptidoglycan

93. Gram-positive vs. gram-negative bacteria

94. Why?
Bacterial cell wall is composed of 1 or 2 bilayers and peptidoglycan shell
Gram-positive: One bilayer and thick peptidoglycan outer shell
Gram-negative: Two bilayers with thin peptidoglycan shell in between

95. How? Gram-positive: pentaglycine bridge connects tetrapeptides
Gram-negative: direct amide bond between tetrapeptides

96. Glycoproteins
The carbohydrates of glycoproteins are linked to the protein component through either O-glycosidic or N-glycosidic bonds
The N-glycosidic linkage is through the amide group of asparagine (Asn, N)
The O-glycosidic linkage is to the hydroxyl of serine (Ser, S), threonine (Thr, T) or hydroxylysine (hLys)

97. Types of protein-linked sugars
Glucose (Glc)
Galactose (Gal)
Mannose (Man)
Fucose (Fuc)
N-acetylgalactosamine (GalNAc)
N-acetylglucosamine (GlcNAc)
N-acetylneuraminic acid (NANA)

98. Significance of protein-linked sugars
Soluble proteins as well as membrane proteins
Purpose:
Protein folding
Protein targeting
prolonging protein half-life
Cell-cell communication
Signaling

99. Blood typing Three different structures: The difference: A, B, and O
N-acetylgalactosamine (for A)
Galactose (for B)
None (for O)

100. Sialic acid N-acetylneuraminate
Precursor: the amino sugar, neuraminic acid
Location: a terminal residue of oligosaccharide chains of glycoproteins
Effect?