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Biochemistry 153A
Professor Richard L. Weiss
Fall 2013
INTRODUCTION
Biochemistry
The Study of Life on the Molecular Level
Bio = Life

Chemistry = Property of Molecules
Biochemistry
Chemistry of Life
What are the chemical and three-dimensional structures of
biological molecules?
How do biological molecules interact with each other?
How does the cell synthesize and degrade biological
molecules?
How is energy conserved and used in the cell?
What are the mechanisms for organizing biological molecules
and coordinating their activities?
How is genetic information stored, transmitted, and
expressed?
What You Will Learn in 153A
Composition, structures and functions of
biomolecules
Principles of enzyme catalysis
Central metabolic pathways of energy
transduction
Beginning of an understanding of the
integrated picture of life and its basis in
chemistry.
Composition, Structures, and
Functions of Biomolecules
Micromolecules
Macromolecules
Proteins
Carbohydrates
Lipids
Nucleic Acids
2
Principles of Enzyme Catalysis
The role of proteins as enzymes
Enzyme kinetics
Catalytic mechanisms
Regulation of enzyme catalysis
Central Metabolic Pathways of Energy
Transduction
Glycolysis
Tricarboxylic Acid Cycle
(TCA Cycle; Krebs Cycle; Citric Acid Cycle)
Electron Transport
Oxidative Phosphorylation
Integration of Biological Processes
What happens
How it happens
When it happens
Why it happens
Coordination | Regulation | Signaling
Intracellular Signaling
Intercellular Signaling
Properties of Life
(Norman Horowitz)
Replication
Catalysis
Mutability
Organisms
Distinguishing Features of Living
Organisms
Chemical Complexity and Microscopic Organization
Systems for Extracting, Transforming, and Using
Energy from the Environment
Defined Functions for each Component and
Regulated Interactions Among Them
Mechanisms for Sensing and Responding to
Alterations in Surroundings
Capacity for Precise Self-Replication and
Assembly
Capacity to Change over Time by Gradual Evolution
Basis for Life

Cells
Prokaryotes: lack nucleus
Eukaryotes: membrane-enclosed nucleus
3
Prokaryotes
(e.g. Escherichia coli)
Adapted to fluctuating
environments
Prokaryotic Cell
Eukaryotes
(e.g. Saccharomyces cerevisiae or human cells)
Adapted to stable environments
Eucaryotic Cell
Eukaryotes
(Differences with Procaryotes)
Increased complexity: >10,000 rxns
vs. ~3,000 rxns
Increased size: 10
3
10
6
x volume
Smaller surface:volume ratio
Membrane-enclosed organelles
Increased solvent capacity
Increased membrane surface
Compartmentation
Evolutionary Relationships
4
Fundamental Similarity of
Biological Processes
Prokaryotes

Eukaryotes
Advantages of Studying
Microorganisms
Ethics
Availability of large numbers of identical
individuals
Ease of manipulation
Genetics
Molecular Biology
Inexpensive
Principles of Biochemistry
(1) Genetic Theory
(2) Central Dogma (of Molecular Biology)
(3) Enzyme Theory
(4) Energy Theory
(5) Spontaneous Self-Assembly Theory
Genetic Theory
DNA as the Genetic Material
Figure 3-13
Central Dogma
(of Molelcular Biology)
Enzyme Theory
Reactants Products
Enzymes
5
Energy Theory
(Biological Transformations)
Biological processes require the
acquisition and utilization of energy
Energy Flow in the Biosphere
Energy Currency
ATP
N
N
N
N
O
OH OH
NH
2
CH
2
O P O P O P

O
O O O
O

Adenine
Ribose
Triphosphate
Metabolic Energy Sources
Autotrophs (self-feeding): synthesize all
cellular constituents
Chemolithotrophs: oxidation of inorganic compounds
Photoautotrophs: photosynthesis
Heterotrophs (other-feeding): dependent on
autotrophs - oxidation of organic compounds
Obligate aerobes
Facultative anaerobes
Obligate anaerobes
Photosynthesis
(Photoautotrophs)
6 CO
2
+ 6 H
2
O C
6
H
12
O
6
+ 6 O
2
Light
Energy
(light-driven reduction of CO
2
)
ADP + P
i
ATP
Light
Energy
(light-driven production of ATP)
Breakdown of Carbohydrates
(Heterotrophs)
C
6
H
12
O
6
+ O
2
6 CO
2
+ 6 H
2
O + energy (ATP)
(energy-yielding oxidation of glucose)
6
Anabolism and Catabolism
(Heterotrophs)
Catabolism
(Oxidation)
ADP
ATP
NADP
+
NADPH
Intermediates
Anabolism
(Biosynthesis)
Proteins
Fats
Carbohydrates
(Nutrients)
Waste
(CO
2
/Urea/etc.)
Spontaneous Self-Assembly
Theory

micromolecules > macromolecules
macromolecules > macromolecular assemblies
macromolecular assemblies > organelles
organelles > cells
cells > tissues and organs
tissues and organs > organisms

Characteristics of Biomolecules
(1) Self-Replication
(2) Self-Assembly
(3) Self-Regulation
Self-Replication
(Based on Templates)
Template
Template Complement
Complement
Complementarity
Complementarity within Molecules
Physical Complementarity
Chemical Complementarity
Self-Assembly
Micromolecules > Macromolecules

Macromolecules > Macromolecular Assemblies
7
Self-Regulation
Dynamic Steady-State
Catalysts > Control > Self-Regulation
Output
Output
Output
Input
D
C
B
A
Complexity of Biomolecules
Requirement for Structural
Diversity
Composition of a Typical Bacterial
Cell
Component Avg. MW Var i ety (#) Complexity
Micromolecules
H
2
O 18 1 1 8
Inorganic Ions 4 0 1 2 4 8 0
Organic Compounds 2 0 0 5 0 0 1 .0 x 10
5
Macromolecules
Proteins 40,000 3 0 0 0 1 .2 x 10
8
DNA 10
9
1 1 0
9
RNA 1 x 10
6
1 000 1 0
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Simply learning structures appears to be a
monumental task!
Principle of Structural Simplicity
Polymerization
Macromolecules (many)
[Polymers]
Precursors (few)
H
2
O
Biopolymers
Types
Homopolymers
Heteropolymers
Length and Branching
Linear homopolymers
Branched homopolymers
Linear heteropolymers
Branched heteropolymers
Homopolymers
Linear Homopolymer
Branched Homopolymer


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Heteropolymers
Linear Heteropolymer
Branched Heteropolymer


Biological Macromolecules
Four Major Classes
Proteins
(Amino Acids)
H
2
N C C
R
1
H
N C COOH
R
2
H
H
2
N C C
R
1
H
O
N C COOH
R
2
H H
O
OH
H
H
Amino Acid Amino Acid Protein
H
2
O
Only 20 naturally-occurring amino acids
Only linear structures
Polysaccharides
(Sugars)
Only a few sugars (~8)
Linear and branched molecules
O
HO
CH2OH
OH
OH
O
CH2OH
OH
OH
OH
O
O
HO
CH2OH
OH
OH
OH
O
HO
CH2OH
OH
OH
OH
Disaccharide (Monosaccharide)
Cellobiose Glucose Glucose
H2O
Lipids (Various Precursors)
Neutral Lipids
H
2
C OH
HC OH
H
2
C OH
R
1
COOH H
2
C O
R
3
COOH
HC R
2
COOH
C
H
2
C
R
1
O C R
2
O C R
3
O
O
O
+
+
+
Glycerol Fatty Acids Triacylglycerol
(Neutral Lipid)
3 H
2
O
Lipids (Various Precursors)
Phospholipids
Phospholipid
Glycerol
Fatty Acids
Phosphate
Alcohol
H
2
C O
HC
C
H
2
C
R
1
O C R
2
O C R
3
O
O
O
H
2
C O
HC
C
H
2
C
R
1
O C R
2
O P O
O
O
O
R
3
O
-
Neutral Lipid
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Nucleic Acids
(Nucleotides)
N
N
N
N
N
N
O
O
OH
O
OH
CH2
O
O P
O
NH2
OH OH
O
O P
O
O
P O
O
O
CH2 O P
O
O
O P
O
O
O P O
O
O
N
N
O
O
OH
O
OH
CH2
O
P O O
O
N
N
N
N
O
NH2
OH
CH2 O P
O
O
O P
O
O
O P O
O
O
OH P
O
O
O P O
O
O
O
Ribonucleotides
Nucleic
Acids
Dinucleotide
Combinations
e.g.
Glycoproteins
Glycolipids
Macromolecules are composed of
polymers of a few simple
precursor molecules
Structural Diversity
Proteins
aa
1
aa
2
aa
3
!aa
n

Number of structures = 20
n

~100 amino acids per molecule

20
100
molecules
Nucleic Acids
N
1
N
2
N
3
!N
n

Number of structures = 4
n

1,000,000 nucleotides per DNA molecule

4
1,000,000
molecules!!!
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Polysaccharides
Homopolymers and Heteropolymers
Many different sugar molecules
Linear and branched

Many different molecules!!!
Lipids
Many complex molecules!!!
Simple construction provides an
immense number of possible
structures fully capable of
providing the necessary diversity
required for life.
Thermodynamic Principles
A Review
Thermodynamics
Energy and Its Effects on
Matter
Thermodynamic Principles
Thermodynamics determines whether
a physical process is possible (i.e.
spontaneous)
Themodynamics provides no
information about the rate of a
physical process
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Thermodynamic Systems
Closed: Physical Chemistry (Equilibrium)



Open: Biochemistry (Steady-State)
A B

A B

Inputs and Outputs
First and Second Laws of
Thermodynamics
First Law of Thermodynamics
Energy is Conserved

Second Law of Thermodynamics
The Universe Tends Toward
Maximum Disorder
Consequences of Second Law of
Thermodynamics
Spontaneous processes proceed in
directions that increase the overall
disorder of the universe
Increased order in a system requires
decreased order of the surroundings
Free Energy
Indicator of Spontaneity
(of Biological Processes)
Gibbs Free Energy (G)
(Constant Pressure)
G = H TS
H = Enthalpy (Heat Content)
S = Entropy (Disorder)
A > B
!G = G
B
G
A

!G = !H T!S
Change in Gibbs Free Energy (!G)
Exergonic: spontaneous

Endergonic: requires input of energy
12
Change in Enthalpy (!H)
Exothermic: system releases heat

Endothermic: system gains heat
[energy of bonds being broken]
minus
[energy of bonds being formed]
Change in Entropy (!S)
[freedom of motion of products]
minus
[freedom of motion of reactants]
Change in Entropy (!S)
Reaction Progress
and
Thermodynamics
Time Course of Reaction
Time
A or B
B
A
Equilibrium
t
1/2
(half-life)
A > B
Transition State
Br
H
H
HO C
H
Br
H
HO C
H
H
CH
3
Br + OH

CH
3
OH +

Br

OH
-
+ + Br
-
Reactants "Transition State" Products
C H
H
H
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Thermodynamics of the Transition State

A + B > P + Q
Accelerating Chemical Reactions
(Heat)
Energy
#
molecules
(slow)
Ea
(fast)
Ea
Heat
!G
!G

Accelerating Chemical Reactions

(Catalysis Reduces !G

)
Chemical Equilibria
Equilibrium Constants
cC + dD aA + bB

!G = !G + RT ln
[C]
c
[D]
d
[A]
a
[B]
b

!G = !G + RT ln K
eq

at equilibrium, !G = 0, and
!G = RT ln Keq

Standard Free Energy Changes
(Standard State Conventions)
One Molar
25C
1 Atmosphere
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Standard State Conventions in
Biochemistry
[H
2
O] = 1
(actual value = 55.5 M incorporated into K
eq
)

[H
+
] = 10
7
M (pH = 7)
Coupled Reactions
Additivity of Free Energy
Changes
Coupled Reactions
!G
o
(kJ/mol)
Fructose-6-P + Pi > Fructose-1,6-bisP + H
2
O 13.3
ATP + H
2
O > ADP + P
i
-30.5
Fructose-6-P + ATP > Fructose-1,6-bisP + ADP -17.2