1. The Structure and Function of Macromolecules
Chapter 5
The Structure and Function of Macromolecules

2. The Molecules of Life Overview:
Another level in the hierarchy of biological organization is reached when small organic molecules are joined together
Atom ---> molecule --- compound

3. Macromolecules Are large molecules composed of smaller molecules
Are complex in their structures
Figure 5.1

4. Macromolecules Most macromolecules are polymers, built from monomers
Four classes of life’s organic molecules are polymers
Carbohydrates
Proteins
Nucleic acids
Lipids

5. A polymer
Is a long molecule consisting of many similar building blocks called monomers
Specific monomers make up each macromolecule
E.g. amino acids are the monomers for proteins

6. The Synthesis and Breakdown of Polymers
Monomers form larger molecules by condensation reactions called dehydration synthesis
(a) Dehydration reaction in the synthesis of a polymer HO H 1 2 3 4
H2O
Short polymer
Unlinked monomer
Longer polymer
Dehydration removes a water molecule, forming a new bond
Figure 5.2A

7. The Synthesis and Breakdown of Polymers
Polymers can disassemble by
Hydrolysis (addition of water molecules)
(b) Hydrolysis of a polymer HO 1 2 3 H 4
H2O
Hydrolysis adds a water molecule, breaking a bond
Figure 5.2B

8. Although organisms share the same limited number of monomer types, each organism is unique based on the arrangement of monomers into polymers
An immense variety of polymers can be built from a small set of monomers

9. Carbohydrates Serve as fuel and building material
Include both sugars and their polymers (starch, cellulose, etc.)

10. Sugars Monosaccharides Are the simplest sugars Can be used for fuel
Can be converted into other organic molecules
Can be combined into polymers

11. Examples of monosaccharides
Triose sugars (C3H6O3)
Pentose sugars (C5H10O5)
Hexose sugars (C6H12O6)
H C OH
H C OH
HO C H
H C OH
C O
HO C H H C O
Aldoses
Glyceraldehyde
Ribose
Glucose
Galactose
Dihydroxyacetone
Ribulose
Ketoses
Fructose
Figure 5.3

12. Monosaccharides May be linear Can form rings 4C 3 2 OH Figure 5.4
H C OH
HO C H
H C O C 1 2 3 4 5 6 OH 4C
6CH2OH 5C
H OH
2 C 1C
3 C 2C
1 C
CH2OH HO
(a) Linear and ring forms. Chemical equilibrium between the linear and ring
structures greatly favors the formation of rings. To form the glucose ring,
carbon 1 bonds to the oxygen attached to carbon 5.
Figure 5.4

13. Disaccharides
Consist of two monosaccharides
Are joined by a glycosidic linkage

14. Figure 5.5 CH2OH O H H OH HO OH H2O
Dehydration reaction in the synthesis of maltose. The bonding of two glucose units forms maltose. The glycosidic link joins the number 1 carbon of one glucose to the number 4 carbon of the second glucose. Joining the glucose monomers in a different way would result in a different disaccharide.
Dehydration reaction in the synthesis of sucrose. Sucrose is a disaccharide formed from glucose and fructose. Notice that fructose, though a hexose like glucose, forms a five-sided ring.
(a)
(b) H HO
H OH OH O
CH2OH
H2O 1 2 4
1– 4 glycosidic linkage
1–2 glycosidic linkage
Glucose
Fructose
Maltose
Sucrose
Figure 5.5

15. Polysaccharides Polysaccharides Are polymers of sugars
Serve many roles in organisms

16. Storage Polysaccharides
Chloroplast
Starch
Amylose
Amylopectin
1 m
(a) Starch: a plant polysaccharide
Figure 5.6
Starch
Is a polymer consisting entirely of glucose monomers
Is the major storage form of glucose in plants

17. (b) Glycogen: an animal polysaccharide
Consists of glucose monomers
Is the major storage form of glucose in animals
Mitochondria
Giycogen granules
0.5 m
(b) Glycogen: an animal polysaccharide
Glycogen
Figure 5.6

18. Cellulose Has different glycosidic linkages than starch
Is a polymer of
glucose
(c) Cellulose: 1– 4 linkage of  glucose monomers H O
CH2OH OH HO 4 C 1
(a)  and  glucose ring structures
(b) Starch: 1– 4 linkage of  glucose monomers
 glucose
 glucose
Figure 5.7 A–C

19. Is a major component of the tough walls that enclose plant cells
Cell walls
Cellulose microfibrils
in a plant cell wall 
Microfibril
CH2OH OH O
Glucose monomer
Parallel cellulose molecules are
held together by hydrogen
bonds between hydroxyl
groups attached to carbon
atoms 3 and 6.
About 80 cellulose
molecules associate
to form a microfibril, the
main architectural unit
of the plant cell wall.
A cellulose molecule
is an unbranched 
glucose polymer.
Cellulose
molecules
Figure 5.8

20. Cellulose is difficult to digest
Cows have microbes in their stomachs to facilitate this process
Figure 5.9

21. Chitin, another important structural polysaccharide
Is found in the exoskeleton of arthropods
Can be used as surgical thread
(a) The structure of the
chitin monomer. O
CH2OH OH H NH C
CH3
(b) Chitin forms the exoskeleton
of arthropods. This cicada
is molting, shedding its old
exoskeleton and emerging
in adult form.
(c) Chitin is used to make a
strong and flexible surgical
thread that decomposes after
the wound or incision heals.
Figure 5.10 A–C

22. Lipids Lipids are a diverse group of hydrophobic molecules Lipids
Are the one class of large biological molecules that do not consist of polymers
Share the common trait of being hydrophobic

23. Fats
Are constructed from two types of smaller molecules, a single glycerol and usually three fatty acids
Vary in the length and number and locations of double bonds they contain

24. Fats Hydrophobic; H bonds in water exclude fats
Carboxyl group = fatty acid
Non-polar C-H bonds in fatty acid ‘tails’
Ester linkage: 3 fatty acids to 1 glycerol (dehydration formation)
Triacyglycerol (triglyceride)

25. Fats
Are constructed from two types of smaller molecules, a single glycerol and usually three fatty acids

26. Fats
Vary in the length and number and locations of double bonds they contain

27. (a) Saturated fat and fatty acid
Saturated fatty acids
Have the maximum number of hydrogen atoms possible
Have no double bonds
(a) Saturated fat and fatty acid
Stearic acid
Figure 5.12

28. (b) Unsaturated fat and fatty acid
Unsaturated fatty acids
Have one or more double bonds
(b) Unsaturated fat and fatty acid
cis double bond
causes bending
Oleic acid
Figure 5.12

29. Phospholipids Have only two fatty acids
Have a phosphate group instead of a third fatty acid

30. (a) Structural formula (b) Space-filling model
Phospholipid structure
Consists of a hydrophilic “head” and hydrophobic “tails”
CH2 O P CH C
Phosphate
Glycerol
(a) Structural formula
(b) Space-filling model
Fatty acids
(c) Phospholipid
symbol
Hydrophobic tails
Hydrophilic
head
Hydrophobic
tails –
Hydrophilic head
Choline +
Figure 5.13
N(CH3)3

31. The structure of phospholipids
Results in a bilayer arrangement found in cell membranes
Hydrophilic
head
WATER
Hydrophobic
tail
Figure 5.14

32. Steroids
Steroids
Are lipids characterized by a carbon skeleton consisting of four fused rings

33. One steroid, cholesterol
Is found in cell membranes
Is a precursor for some hormones HO
CH3
H3C
Figure 5.15

34. Steroid Hormone Mechanism of Action
The steroid hormone mechanism of action can be summarized as follows:
Steroid hormones pass through the cell membrane of the target cell.
The steroid hormone binds with a specific receptor in the cytoplasm.
The receptor bound steroid hormone travels into the nucleus and binds to another specific receptor on the chromatin.
The steroid hormone-receptor complex calls for the production of messenger RNA (mRNA) molecules, which code for the production of proteins.

35. Anabolic steroid hormones
Anabolic steroid hormones are synthetic substances that are related to the male sex hormones. They have the same mechanism of action within the body Anabolic steroid hormones stimulate the production of protein which is used to build muscle. They also lead to an increase in the production of testosterone

36. Anabolic steroid hormones
Testosterone is also critical in the development of lean muscle mass. Anabolic steroid hormones also promote the release of the growth hormone which stimulates growth, especially skeletal growth. Abuse of anabolic steroid hormones disrupt the normal production of hormones in the body

37. Anabolic steroid hormones
There are several negative health consequences associated with anabolic steroid abuse.
Some of these include infertility, hair loss, breast development in males, heart attacks, and liver tumors.

38. Proteins
Proteins have many structures, resulting in a wide range of functions
Proteins do most of the work in cells and act as enzymes
Proteins are made of monomers called amino acids

39. An overview of protein functions
Table 5.1

40. 3 Substrate is converted
Enzymes
Are a type of protein that acts as a catalyst, speeding up chemical reactions
Substrate
(sucrose)
Enzyme
(sucrase)
Glucose OH
H O
H2O
Fructose
3 Substrate is converted
to products.
Active site is available for
a molecule of substrate, the
reactant on which the enzyme acts.
Substrate binds to
enzyme. 2
4 Products are released.
Figure 5.16

41. Polypeptides Polypeptides A protein
Are polymers (chains) of amino acids
A protein
Consists of one or more polypeptides

42. Amino acids
Are organic molecules possessing both carboxyl and amino groups
Differ in their properties due to differing side chains, called R groups

43. Twenty Amino Acids 20 different amino acids make up proteinsH
H3N+ C
CH3 CH
CH2 NH
H2C
H2N
Nonpolar
Glycine (Gly)
Alanine (Ala)
Valine (Val)
Leucine (Leu)
Isoleucine (Ile)
Methionine (Met)
Phenylalanine (Phe)
Tryptophan (Trp)
Proline (Pro)
H3C
Figure 5.17 S
20 different amino acids make up proteins

44. Polar Electrically chargedOH
CH2 C H
H3N+ O
CH3 CH SH
NH2
Polar
Electrically
charged –O
NH3+
NH2+
NH+ NH
Serine (Ser)
Threonine (Thr)
Cysteine
(Cys)
Tyrosine
(Tyr)
Asparagine
(Asn)
Glutamine
(Gln)
Acidic
Basic
Aspartic acid
(Asp)
Glutamic acid
(Glu)
Lysine (Lys)
Arginine (Arg)
Histidine (His)

45. Amino Acid Polymers Amino acids
Are linked by peptide bonds, covalent bonds

46. Protein Conformation and Function
A protein’s specific conformation (shape) determines how it functions

47. Four Levels of Protein Structure
The primary structure of a protein is its unique sequence of amino acids
Secondary structure, found in most proteins, consists of coils and folds in the polypeptide chain
Tertiary structure is determined by interactions among various side chains (R groups)
Quaternary structure results when a protein consists of multiple polypeptide chains
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

48. Four Levels of Protein Structure
Primary structure
Is the unique sequence of amino acids in a polypeptide
Figure 5.20 –
Amino acid subunits
+H3N Amino end o
Carboxyl end c
Gly
Pro
Thr
Glu
Seu
Lys
Cys
Leu
Met
Val
Asp
Ala
Arg
Ser
lle
Phe
His
Asn
Tyr
Trp
Lle
Primary structure is determined by inherited genetic information

49. Secondary structure
Is the folding or coiling of the polypeptide into a repeating configuration
Includes the  helix and the  pleated sheet O C
 helix
 pleated sheet
Amino acid subunits N H R H

50. Secondary structure

51. Tertiary structure
Is the overall three-dimensional shape of a polypeptide
Results from interactions between amino acids and R groups
Strong covalent bonds called disulfide bridges may reinforce the protein’s structure

52. Hydrophobic interactions and van der Waals interactions
CH2 CH
O H O C HO
NH3+ -O S
CH3
H3C
Hydrophobic interactions and van der Waals interactions
Polypeptide backbone
Hyrdogen bond
Ionic bond
Disulfide bridge

53. Quaternary structure
Is the overall protein structure that results from the aggregation of two or more polypeptide subunits
Hemoglobin is a globular protein consisting of four polypeptides: two alpha and two beta chains
Polypeptide chain
Collagen
 Chains
 Chains
Hemoglobin
Iron
Heme

54. Sickle-Cell Disease: A Simple Change in Primary Structure
Results from a single amino acid substitution in the protein hemoglobin

55. Fig. 5-22
Normal hemoglobin
Sickle-cell hemoglobin
Primary
structure
Primary
structure
Val
His
Leu
Thr
Pro
Glu
Glu
Val
His
Leu
Thr
Pro
Val
Glu 1 2 3 4 5 6 7 1 2 3 4 5 6 7
Exposed
hydrophobic
region
Secondary
and tertiary
structures
Secondary
and tertiary
structures
 subunit
 subunit    
Quaternary
structure
Normal
hemoglobin
(top view)
Quaternary
structure
Sickle-cell
hemoglobin    
Function
Molecules do
not associate
with one
another; each
carries oxygen.
Function
Molecules
interact with
one another and
crystallize into
a fiber; capacity
to carry oxygen
is greatly reduced.
Figure 5.22 A single amino acid substitution in a protein causes sickle-cell disease
10 µm
10 µm
Red blood
cell shape
Normal red blood
cells are full of
individual
hemoglobin
moledules, each
carrying oxygen.
Red blood
cell shape
Fibers of abnormal
hemoglobin deform
red blood cell into
sickle shape.

56. What Determines Protein Conformation?
Protein conformation Depends on the physical and chemical conditions of the protein’s environment
Temperature, pH, etc. affect protein structure

57. Denaturation is when a protein unravels and loses its native conformation (shape)
Renaturation
Denatured protein
Normal protein
Figure 5.22

58. The Protein-Folding Problem
Most proteins
Probably go through several intermediate states on their way to a stable conformation
Denaturated proteins no longer work in their unfolded condition
Proteins may be denaturated by extreme changes in pH or temperature

59. Protein folding Chaperones
In eukaryotes, proteins may need to remain unfolded long enough to be transported across the cell memebrane
Special proteins called CHAPERONES aid in the correct and timely folding of other proteins

60. Heat-shock proteins (Hsps) are molecular chaperones that are induced when organisms are exposed to high temperatures and other stresses. These stresses cause proteins to unfold and potentially aggregate, thereby creating a protein-folding crisis in the cell.
Hsp chaperones help the cell cope with this crisis by binding different types of folding intermediates and interacting with them in different ways.

61. HSPs
Completion of correct folding requires the release from the chaperone and is driven by ATP hydrolysis
About 85% fold using chaperones
(ATP hydrolysis is the reaction by which chemical energy that has been stored and transported in the high-energy phosphoanhydridic bonds in ATP (Adenosine triphosphate) is released)

62. Chaperonins Involved in the 15% of protein folding
Large multisubunit proteins that form a cage (cavity) around the protein to protect it during folding
During folding, polypeptide chain goes through cycles of binding and unbinding to surface of cavity
Also uses ATP hydrolysis

63. Chaperonins Hollow cylinder Cap Chaperonin (fully assembled)
Steps of Chaperonin Action: An unfolded poly- peptide enters the cylinder from one end.
The cap attaches, causing the cylinder to change shape in such a way that it creates a hydrophilic environment for the folding of the polypeptide.
The cap comes off, and the properly folded protein is released.
Correctly folded protein
Polypeptide 2 1 3
Figure 5.23

64. X-ray crystallography
Is used to determine a protein’s three-dimensional structure
X-ray diffraction pattern
Diffracted X-rays
X-ray source
X-ray beam
Crystal
Nucleic acid
Protein
(a) X-ray diffraction pattern
(b) 3D computer model
Figure 5.24

65. Nucleic Acids Nucleic acids store and transmit hereditary information
Genes
Are the units of inheritance
Program the amino acid sequence of polypeptides
Are made of nucleotide sequences on DNA

66. The Roles of Nucleic Acids
There are two types of nucleic acids
Deoxyribonucleic acid (DNA)
Ribonucleic acid (RNA)

67. Deoxyribonucleic Acid
DNA
Stores information for the synthesis of specific proteins
Found in the nucleus of cells

68. Synthesis of mRNA in the nucleus
DNA Functions
Directs RNA synthesis (transcription)
Directs protein synthesis through RNA (translation) 1 2 3
Synthesis of mRNA in the nucleus
Movement of
mRNA into cytoplasm
via nuclear pore
Synthesis
of protein
NUCLEUS
CYTOPLASM
DNA
mRNA
Ribosome
Amino acids
Polypeptide
Figure 5.25

69. The Structure of Nucleic Acids
5’ end
5’C
3’ end OH
Figure 5.26 O
Nucleic acids
Exist as polymers called polynucleotides
(a) Polynucleotide,
or nucleic acid

70. Each polynucleotide Consists of monomers called nucleotides
Sugar + phosphate + nitrogen base
Nitrogenous
base
Nucleoside O O O P
CH2
5’C
3’C
Phosphate
group
Pentose
sugar
(b) Nucleotide
Figure 5.26

71. (c) Nucleoside components
Nucleotide Monomers
Nucleotide monomers
Are made up of nucleosides (sugar + base) and phosphate groups CH
Uracil (in RNA) U
Ribose (in RNA)
Nitrogenous bases Pyrimidines C N O H
NH2 HN
CH3
Cytosine
Thymine (in DNA) T HC NH
Adenine A
Guanine G
Purines
HOCH2 OH
Pentose sugars
Deoxyribose (in DNA) 4’ 5” 3’ 2’ 1’
Figure 5.26
(c) Nucleoside components

72. Nucleotide Polymers Nucleotide polymers
Are made up of nucleotides linked by the–OH group on the 3´ carbon of one nucleotide and the phosphate on the 5´ carbon on the next

73. Gene The sequence of bases along a nucleotide polymer
Is unique for each gene

74. The DNA Double Helix Cellular DNA molecules
Have two polynucleotides that spiral around an imaginary axis
Form a double helix

75. The DNA double helix Consists of two antiparallel nucleotide strands
3’ end
Sugar-phosphate backbone
Base pair (joined by hydrogen bonding)
Old strands
Nucleotide about to be added to a new strand A
5’ end
New strands
Figure 5.27

76. A,T,C,G The nitrogenous bases in DNA
Form hydrogen bonds in a complementary fashion (A with T only, and C with G only)

77. DNA and Proteins as Tape Measures of Evolution
Molecular comparisons
Help biologists sort out the evolutionary connections among species