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MCB 3020, Spring 2005
1-10-2004
Chapter 3:
The Building Blocks of Life I
Chapter 3
I. The chemistry of life
II. Macromolecules of the cell
A. polysaccharides
B. lipids
C. nucleic acids
D. proteins
2
The Chemistry of Life
All cells are made of organic molecules.
membrane
lipids
3
OCH2-CH2 CH2- O-P=O
O O
OR
C=O C=O
CH2 CH2
CH2 CH2
CH2 CH2
CH2 CH2
CH2 CH2
CH2 CH2
CH2 CH2
CH2 CH2
CH2 CH2
CH2 CH2
CH2 CH2
CH2 CH2
CH2 CH2
CH2 CH2
CH3 CH3
I. The Chemistry of Life: a review
A. the 6 major bioelements
B. charge distribution in molecules
C. attractive forces
D. important functional groups
4
A. The 6 Major Bioelements
C
H
O
N
P
S
Carbon
Hydrogen
Oxygen
Nitrogen
Phosphorus
Sulfur
5
B. Charge distribution in molecules
1. electronegativity
2. hydrophilic (polar)
3. hydrophobic (nonpolar)
4. amphipathic
6
1. Electronegativity
7
A measure of the degree of attraction
of valence electrons
Among the major bioelements
oxygen and nitrogen have the highest
electronegativity
TB
2. Polar (hydrophilic)
8
-
+
asymmetric charge distribution in a molecule
d+ d-
H - O - CH2 CH3
TB
Polar molecules
d+
d-
d+
H-O-H
9
d-
O
H-Cd+
O
Polar molecules result from the bonding of
atoms with very different electronegativities
TB
3. Nonpolar (hydrophobic)
10
little charge asymmetry
TB
Nonpolar molecules
11
hydrocarbon
chain
aromatic rings
Nonpolar molecules result from the bonding of
atoms with similar electronegativities.
TB
12
4. Amphipathic
partly polar, partly nonpolar
phospholipid molecule
negatively
charged
head
nonpolar
hydrocarbon
tail
TB
C. Attractive forces
1. ionic bonds
2. covalent bonds
3. hydrogen bonds
4. van der Waals forces
5. hydrophobic interactions
6. comparison of bond strengths
13
1. Ionic bonds
attraction between charged particles
14
NaCl
+
Na
••••
Cl
2. Covalent bonds
electron sharing between atoms
••
••
H
••
H
H C
••
H
H
H– C – H
H
3. Hydrogen bonds (H-bonds)
noncovalent bonds formed between
the following:
15
1. A highly electronegative atom
(usually O or N)
2. A hydrogen atom bonded to
a highly electronegative atom
(usually O or N)
TB
Hydrogen bonding of water molecules
16
H
H
O
O
H
O
H
H
H
H-bonding of hydroxyl groups
R O H O R
H
H-bonding of amino groups
R
R
R— N
N
R
R
Keto groups
R
H
17
O
H O
R
H-bonds will form with various combinations
of hydroxyl, amino and keto groups that
meet the H-bonding criteria.
TB
Hydrogen bonding between amino
acids in a protein
|
H-C-R1
|
C=O
|
N-H
|
H-C-R2
|
C=O
|
N-H
|
H-C-R3
|
|
R4-C-H
|
H –N
|
O=C
|
R5-C-H
|
H –N
|
O=C
|
Rc- C-H
|
18
19
Hydrogen bonding between bases in DNA
guanine
cytosine
Three H-bonds between G and C
4. van der Waals forces
Attraction between molecules that
are very close together
20
nucleus
+
-
+
electrons
induced dipoles (polar)
van der Waals attractions result from
attractions between induced dipoles
TB
21
5. Hydrophobic forces (interactions)
Attraction between hydrophobic
molecules or hydrophobic portions of
molecules
• driven by an increase in entropy
(disorder) due to water exclusion TB
Water is the biological solvent of life
as we know it.
• cells are 70 to 90% water
• water is polar
• many polar biological molecules
dissolve in water
• nonpolar (hydrophobic) molecules
tend to aggregate together in water
22
6. Comparison of bond strength
type of bond
1. Covalent bonds
2. ionic bonds
3. hydrogen bonds
4. van der waals forces
5. hydrophobic forces
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strength (kcal/mol)
-50 to -100
-80 or -1
-3 to -6
-0.5 to -1
-0.5 to -3
D. Important functional groups
24
Biological importance
carboxylic
acid
organic acids,
amino and fatty acids
aldehyde
reducing sugars,
like glucose
alcohol
lipids and
carbohydrates
Important functional groups (contd.)
25
keto
pyruvate,
citric acid cyle
intermediates
ester
lipids of Bacteria
and Eukarya
phosphoester
DNA, RNA,
ATP
Important functional groups (contd.)
ether
amino
lipids
(archaea)
NH2
amino acids,
nucleotides
26
What functional groups are present
in the amino acid serine?
OH
CO
H2N – C – H
CH2OH
OCO
+H N – C – H
3
CH2OH
serine at pH 7
27
II. Macromolecules of the cell
A. polysaccharides
B. lipids
C. nucleic acids
D. proteins
28
Monomers and polymers
29
macromolecules are polymers of
covalently linked monomers
monomer
(eg. amino acid)
covalent bond
polymer (eg. protein)
Macromolecules are large molecules
made of repeating units (monomers).
DNA
a protein
a nucleic acid: a chain
(polymer) of nucleotides
a polymer of
amino acids
30
Macromolecules make up 96% of
the dry weight of cells.
polysaccharides
proteins
lipids
nucleic acids
31
The 4 major cellular macromolecules*: 32
chains (polymers) of repeating units
polymer
monomer
polysaccharide sugars
example
covalent bond
cell wall
glycosidic
(see notes for
other examples)
lipid
fatty acids or membranes ester or ether
isoprenoids
nucleic acid
nucleotides
protein
amino acids enzymes
*Important recurring theme
DNA, RNA phosphodiester
peptide
B. Polysaccharides
polymers of sugars linked by
glycosidic bonds
1. common sugar monomers
2. glycosidic bonds
3. cellular polysaccharides
33
34
1. common sugar monomers
a. glucose
(ring form)
b. fructose
(ring form)
CH2OH
O
OH
HO
HOH2C
O
OH
OH
CH2OH
HO OH
HO
TB
HOH2C
35
O
c. ribose
OH
HO
HOH2C
d. deoxyribose
HO
O
OH
HO
TB
CH2OH
O
e. glucosamine
HO
36
OH
OH
NH2
CH2OH
O
f. muramic acid
OH
HO
-OOCCHCH
3
NH2
TB
2. Glycosidic bonds:
a. -1,4-glycosidic bond
CH2OH
O
CH2OH
O OH
H
H
O
OH
HO
OH
37
OH
OH
38
b. -1,4-glycosidic bond
CH2OH
O
OH
HO
H
OH
O
CH2OH
O OH
H
OH
OH
39
3. cellular polysaccharides
a. starch
-1,4 glycosidic bonds
large polymer of glucose
mostly -1,4 glycosidic bonds
glucose storage molecule of plants
TB
40
b. glycogen
-1,6
-1,6
large branched polymer of glucose
mostly -1,4 glycosidic bonds
-1,6 glycosidic bonds produce
branching
glucose storage molecule of animals
and some microorganisms
TB
c. cellulose
41
large glucose polymer
major structural polysaccharide
of plants
mostly b-1,4 glycosidic bonds
only microbes can break the b-1,4 bond
TB
d. peptidoglycan
42
large polymer of N-acetyl glucosamine
and N-acetyl muramic acid
the main structural component of
most Bacterial cell walls
b-1,4-glycosidic bonds
*Penicillin inhibits Bacterial cell wall synthesis
by inhibiting the formation of peptidoglycan. TB
Study objectives
43
1. Memorize the 6 major bioelements.
2. Understand the terms electronegativity, hydrophilic, hydrophobic,
polar, nonpolar, amphipathic. Know how these properties are important in
chemical bonds and interactions.
3. Very important recurring theme: Understand the attractive forces (ionic,
covalent, hydrogen bonds, van der Waals forces, and hydrophobic
interactions), the examples presented in class, where they might occur.
Which are strong bonds? Which are weaker?
4. Understand the role of water as the solvent of life.
5. Know the functional groups. Be able to recognize their structures. Know
their biological importance and where they occur in cellular molecules.
6. Recurring theme: Know the four important cellular macromolecules
(polymers), the monomers that comprise them, the bonds that connect the
monomers, and the specific example presented in class. These
macromolecules are the building blocks of cells.
7. In what parts of cells are the four macromolecules found?
Study objectives
44
8. Describe the structure and functions of the four cellular macromolecules,
the monomers, connecting bonds. Memorize the specific
examples of monomers, polymers, and bonds presented in class.
9. Be able to recognize the structures of glucose, ribose, and deoxyribose.
10. Know the difference between -1,4 glycosidic bonds and b-1,4-glycosidic
bonds and where they can be found. Know the features of the cellular
polysaccharides presented. How does penicillin inhibit microbial growth? 8.
45
MCB 3020, Spring 2004
1-14-2004
Chapter 2
The Building Blocks of Life II:
Chapter 2 (contd.)
II. Macromolecules of the cell
A. polysaccharides
B. lipids
C. nucleic acids
D. proteins
46
B. Lipids
1. fatty acids (glycerol)
2. membrane lipids
a. bacterial and eukaryal
b. archaeal
47
B. Lipids
glycerol bonded to fatty acids
(or isoprenoid units) and other
groups by ester or ether linkages
CH2OH
CHOH
CH2OH
glycerol
O
HO - C
48
1. Fatty acids
a. common fatty acids
palmitic (C16)
stearic (C18)
49
COO
COO-
oleic (C18)
COOa monounsaturated fatty acid
TB
b. saturated and unsaturated fatty acids50
saturated: no double bonds
COO-
monounsaturated: 1 double bond
polyunsaturated: > 1 double bond
COO-
Unsaturated fatty acids can make
the membrane more fluid.
51
52
2. Membrane lipids:
glycerol phosphate bonded to fatty acids
and other groups by ester or ether bonds
Membrane lipids are amphipathic.
polar head
hydrophobic tail
In aqueous solution lipids associate
spontaneously to form bilayers that are the
basis of biological membranes
53
The polar heads are in contact with water the
nonpolar tails group with one another.
a. bacterial and eukaryal membrane
lipids
fatty acids connected to glycerol
phosphate through ester bonds
54
phosphatidic acid
phosphatidyl ethanolamine
phosphatidyl serine
TB
55
phosphatidic acid
ester bond
o
-o- o
-ooo P o
o-
fatty acid
TB
56
phosphatidyl ethanolamine
o
-o- o
-o-
o
oP
fatty acid
o
o- CH2CH2NH3+
ethanolamine
o-CH2CH2CHCOOserine
NH3+
TB
b. archaeal lipids
57
isoprenoid units connected to glycerol
phosphate through ether bonds
ether bond -C-O-C-
-O-OOH
polar
nonpolar
TB
C. Nucleic acids (DNA, RNA)
polymer of nucleotides covalently
linked by phosphodiester bonds
DNA
RNA
58
1. Nucleotides =
a. Base
+
purines:
adenine (A)
guanine (G)
thymine (T) (DNA only)
cytosine (C)
uracil (U) (RNA only)
pyrimidines
59
sugar
+ phosphate(s)
(up to 3)
HOCH2
ribose (RNA)
deoxyribose
(DNA)
OCH2
O— P=O
O-
Detailed picture of a nucleotide (ATP)
NH2
5' phosphate end
N
N
O
-O
O
O
-P - O - P – O - P –
O-
O-
60
5'
O-CH2
O-
OH
3' hydroxyl
N
O
OH
N
adenosine
triphosphate
(ATP)
b. phosphodiester bonds
61
5'
5' phosphate
O
sugars of the
nucleotides are
covalently linked
by phosphodiester
bonds
3'
O
base
5'
H
O = P - OO-CH2
O base
3'
3' hydroxyl
OH
H
3'
62
c. Nitrogen bases
purines
adenine
guanine
pyrimidines
cytosine
thymine
uracil
63
Purines
adenine
guanine
NH2
N
N
H
N
N
O
N
N
H
NH
N
NH2
TB
64
Pyrimidines
cytosine
NH2
thymine
O
N
N
H
uracil
O
NH
O
N
H
O
NH
N
H
O
in RNA TB
2. DNA structure
a. double-stranded helix
b. sugar-phosphate backbone
*sugar = deoxyribose
c. nucleotide bases pair through
hydrogen bonds between the
helical strands
d. the sequence of the bases is the
"primary structure"
65
c. nucleotide base pairing
The most stable complementary DNA
base pairing pattern is called "WatsonCrick base pairing" where A=T and GC
Two H-bonds between T and A
66
c. nucleotide base pairing
guanine
67
cytosine
Three H-bonds between G and C
d. DNA sequence (primary structure)
DNA carries genetic information in
the sequence of the bases.
transcription
translation
DNA

mRNA

protein
68
AAA…

UUU…

phenylalanine
(an amino acid)
69
3. RNA structure
• RNA is usually single stranded (ssRNA)
• ribose instead of deoxyribose
• uracil instead of thymine
• primary structure = the base sequence
• secondary structure = complementary
base pairing in a single RNA molecule
•GC A=U
ssRNA
intramolecular
base pairing RNA stem-loop
RNA secondary structure
A-G-A-C-A-A-A-C-C-G-U-C-A
A A
A
C
A
A- G
70
C
C
G
U
C -A
RNA stem loop
e.g. tRNA stem loops
Functions of the major RNAs
DNA
71
1. messenger RNAs (mRNA) contain mRNA
genetic information to encode a protein
phe
2. transfer RNAs (tRNA) act as adapters
between the mRNA nucleotide code and
amino acids during protein synthesis
3. ribosomal RNAs (rRNA) are structural and
catalytic component of ribosomes, the
protein-synthesizing machinery of cells
D. Proteins
1. general structure
2. the 21 amino acids
3. peptide bonds
4. levels of protein structure
5. stereoisomers
72
D. Proteins
linear chains of L-amino acids
linked by peptide bonds
met leu
his val glu asn asp cys
peptide bond
e.g. enzymes, transport proteins, antibodies
insulin, structural proteins, regulatory
proteins, hair, flagella, viral protein coat
73
1. General structure of L-amino acids
amino
group
-carbon
O
C – OH
H2 N – C – H
R
R-group or
side chain
74
carboxylic acid
O
C
–
O
+
H3N – C – H
R
at pH 7
2. The 21 amino acids encoded by DNA 75
ACIDIC
aspartate
glutamate
BASIC
lysine
arginine
histidine
POLAR, NEUTRAL
asparagine
serine
threonine glutamine
tyrosine cysteine
selenocysteine
NONPOLAR (HYDROPHOBIC)
phenylalanine
glycine leucine
alanine isoleucine tryptophan
valine
methionine proline
Hydrophobic amino acids tend to be
associated with hydrophobic
environments
• membranes
• inside of proteins
Hydrophilic amino
acids are often in
contact with water
Lysozyme
76
a. Acidic amino acids
net negative charge at pH 7
O
C
O
+
H3N - C - H
CH2
COO
aspartate (asp)
77
O
C
O
+
H3N - C - H
CH2
CH2
COO
glutamate (glu) TB
b. Basic amino acids:
78
net positive charge at pH 7
CH2
CH2
CH2
CH2
NH3
+
lysine (lys)
CH2
CH2
CH2
+
NH
CH2
NH
C
H2N NH2
+
arginine (arg)
N
H
histidine (his) TB
79
c. Polar but neutral
CH2
OH
CH- CH3
OH
CH2
CH2
SH
OH
Ser (S)
Thr (T)
Tyr (Y)
Cys (C)
TB
80
c. Polar but neutral (contd.)
CH2
CH2
CH2
C
O
C
NH2
Asn (N)
O
NH2
Gln (Q)
CH2
SeH
Sec (U)
TB
81
d. Nonpolar (hydrophobic)
H
CH3
Gly(G) Ala (A)
CH2
CH
CH
H3C CH3
H3C CH3
Val (V)
Leu (L)
CH CH3
CH2
CH3
Ile (I)
TB
82
d. Nonpolar (hydrophobic)
HN
O
C OH
CH
CH2
CH2
CH2
Pro (P)
CH2
CH2
NH
CH2
CH2
S
CH3
Trp (W)
Phe (F) Met (M)
TB
83
Disulfide bridge
covalent bond between two
sulfhydryl groups (eg. of cysteines)
O
C
O
+
+
H3N - C - H H3N
CH2
S
O
C - O-C-H
CH2
S
disulfide bridges
antibody
selenocysteine: the
st
21
amino acid
84
O
+ C - OH3N - C - H
CH2
SeH
• found in some microbial enzymes
like hydrogenase
3. Peptide bonds join L-amino acids
in proteins
O
H C - OH
H -N - C - H
R2
H2 O dehydration
O
H
C
OH
O
peptide bond
N- C-H
C
R2
H2N - C - H
R1
O
C - OH
H2N - C - H
R1
85
4. Levels of protein structure
a. Primary (1°) structure
amino acid sequence
met leu
his val glu asn asp cys
86
b. Secondary (2°) structure
87
Patterns of folding due to hydrogen bonds
between groups of the peptide backbone
-helix
b-sheet
1. alpha helix (coil)
CH
R
CH
R
N
H
CH
C
N
R
H
N
H
CH
R
C
CH
R
O
O
O
C
O
O
O
C
88
N
H
CH
R
C
N
H
C
N
H
89
2. beta sheet
N
N
R C
R C
C O
H N
C O
H N
C
R
O C
O C
N
C
R
H
N
R C
R C
C O
H N
C O
H N
C
O C
H
C
R
O C
R
c. Tertiary (3°) structure
Native 3-D structure of a protein
hexokinase
90
ribonuclease
Stabilized by H-bonds, hydrophobic
interactions, van der Waals forces,covalent
disulfide bridges, and some ionic bonds
d. Quaternary (4°) structure
association of two or more
polypeptides
-chains
hemoglobin
-chains
91
5. Stereoisomers
Mirror-image compounds with the
same molecular formula
COOH
H2 N - C - H
CH3
L-alanine
COOH
H - C - NH2
CH3
D-alanine
92
Why is this important?
93
In biology,
D-sugars predominate
L-amino acids are found in proteins
D-amino acids are less common,
but are found in bacterial cell
walls and antibiotics
The 4 major cellular macromolecules*: 94
chains (polymers) of repeating units
polymer
monomer
polysaccharide sugars
example
covalent bond
cell wall
glycosidic
(see notes for
other examples)
lipid
fatty acids or membranes ester or ether
isoprenoids
nucleic acid
nucleotides
protein
amino acids enzymes
*Important recurring theme
DNA, RNA phosphodiester
peptide
Study objectives
95
1. Contrast saturated and unsaturated fatty acids. Understand how and why
they influence membrane fluidity. Know the general structure of membrane
lipids. Know the names of the fatty acids and lipids presented in class. You
do NOT need to memorize the structure of the individual fatty acids,
ethanolamine, or serine.
2. Compare and contrast bacterial,eukaryal, and archaeal lipids, especially
the molecular components and the bonds. More details later.
3. What are nucleic acids? Understand that nucleotides are composed of a
nitrogenous base (purine or pyrimidine), a sugar (ribose or deoxyribose),
and one to three phosphates. Know the structure of the phosphodiester
bond. What parts of the nucleotides are connected by the phosphate of the
phosphodiester bond? What is meant by the 5' and 3' ends of DNA and RNA?
4. Memorize the structure of the nucleotide ATP. This is a very important
molecule and we will discuss it in great detail throughout the semester.
5. Know the purines and pyrimidines. Know the number of rings in each.
What is the structural difference between thymine (T) and uracil (U)?