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8/11/2019 Biochemistry Lecture Slides Week 1
1/14
1
Biochemistry 153A
Professor Richard L. Weiss
Fall 2013
INTRODUCTION
BiochemistryThe Study of Life on the Molecular Level
Bio = Life
Chemistry = Property of Molecules
BiochemistryChemistry of Life
What are the chemical and three-dimensional structures ofbiological molecules?
How do biological molecules interact with each other?
How does the cell synthesize and degrade biologicalmolecules?
How is energy conserved and used in the cell?
What are the mechanisms for organizing biological moleculesand coordinating their activities?
How is genetic information stored, transmitted, andexpressed?
What You Will Learn in 153A
Composition, structures and functions ofbiomolecules
Principles of enzyme catalysis
Central metabolic pathways of energytransduction
Beginningof an understanding of theintegrated picture of life and its basis inchemistry.
Composition, Structures, andFunctions of Biomolecules
Micromolecules
Macromolecules
Proteins
Carbohydrates
Lipids
Nucleic Acids
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Principles of Enzyme Catalysis
The role of proteins as enzymes
Enzyme kinetics
Catalytic mechanisms
Regulation of enzyme catalysis
Central Metabolic Pathways of EnergyTransduction
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 LivingOrganisms
Chemical Complexity and Microscopic Organization
Systems for Extracting, Transforming, and UsingEnergy from the Environment
Defined Functions for each Component andRegulated Interactions Among Them
Mechanisms for Sensing and Responding toAlterations in Surroundings
Capacity for Precise Self-Replication andAssembly
Capacity to Change over Time by Gradual Evolution
Basis for Life
Cells
Prokaryotes:lack nucleus
Eukaryotes:membrane-enclosed nucleus
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Prokaryotes(e.g. Escherichia coli)
Adapted to fluctuatingenvironments
Prokaryotic Cell
Eukaryotes(e.g. Saccharomyces cerevisiaeor human cells)
Adapted to stable environments
Eucaryotic Cell
Eukaryotes(Differences with Procaryotes)
Increased complexity: >10,000 rxnsvs. ~3,000 rxns
Increased size: 103 106x volume
Smaller surface:volume ratio Membrane-enclosed organelles
Increased solvent capacity Increased membrane surface
Compartmentation
Evolutionary Relationships
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Fundamental Similarity ofBiological Processes
Prokaryotes
Eukaryotes
Advantages of StudyingMicroorganisms
Ethics
Availability of large numbers of identicalindividuals
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 ProductsEnzymes
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Energy Theory(Biological Transformations)
Biological processes require the
acquisitionand utilizationof energy
Energy Flow in the Biosphere
Energy Currency
ATP
N
N
N
N
O
OHOH
NH2
CH2OPOPOPO
OOO
O O O
Adenine
Ribose
Triphosphate
Metabolic Energy Sources
Autotrophs(self-feeding): synthesize allcellular constituents Chemolithotrophs:oxidation of inorganic compounds Photoautotrophs:photosynthesis
Heterotrophs(other-feeding): dependent onautotrophs - oxidation of organic compounds Obligate aerobes Facultative anaerobes
Obligate anaerobes
Photosynthesis(Photoautotrophs)
6 CO2+ 6 H2O C6H12O6+ 6 O2
Light
Energy
(light-driven reduction of CO2)
ADP + Pi ATP
Light
Energy
(light-driven production of ATP)
Breakdown of Carbohydrates(Heterotrophs)
C6H12O6+ O2 6 CO2+ 6 H2O + energy (ATP)
(energy-yielding oxidation of glucose)
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Anabolism and Catabolism(Heterotrophs)
Catabolism
(Oxidation)
ADP
ATP
NADP+
NADPH
Intermediates
Anabolism
(Biosynthesis)
ProteinsFats
Carbohydrates
(Nutrients)
Waste
(CO2/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
TemplateComplement
Complement
Complementarity
Complementarity within Molecules
Physical Complementarity
Chemical Complementarity
Self-Assembly
Micromolecules > Macromolecules
Macromolecules > Macromolecular Assemblies
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Self-Regulation
Dynamic Steady-State
Catalysts > Control > Self-Regulation
Output
Output
Output
Input
D
C
B
A
Complexity of Biomolecules
Requirement for StructuralDiversity
Composition of a Typical BacterialCell
Component Avg. MW Va ri ety (#) Co mp lexity
Micromolecules
H2O 18 1 1 8
Inorganic Ions 4 0 1 2 4 8 0
Organic Compounds 2 0 0 5 0 0 1 .0 x 105
Macromolecules
Proteins 40,000 3 0 0 0 1 .2 x 108
DNA 109 1 1 09
RNA 1 x 106 1 0 00 1 09
Simply learning structures appears to be amonumental task!
Principle of Structural Simplicity
PolymerizationMacromolecules (many)
[Polymers]Precursors (few)
H2O
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)
H2N C C
R1
H
N C COOH
R2
H
H2N C C
R1
H
O
N C COOH
R2
H H
O
OH
H
H
Amino Acid Amino Acid Protein
H2O
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)
CellobioseGlucoseGlucose
H2O
Lipids (Various Precursors)Neutral Lipids
H2C OH
HC OH
H2C OH
R1 COOH H2C O
R3 COOH
HCR2 COOH
C
H2C
R1
O C R2
O C R3
O
O
O
+
+
+
Glycerol Fatty Acids Triacyl gl ycerol(Neutral Lipid)
3 H2O
Lipids (Various Precursors)Phospholipids
Phospholipid
Glycerol
Fatty Acids
Phosphate
Alcohol
H2C O
HC
C
H2C
R1
O C R2
O C R3
O
O
O
H2C O
HC
C
H2C
R1
O C R2
O P O
O
O
O
R3
O-
Neutral Lipid
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Nucleic Acids(Nucleotides)
N
N
N
N
N
N
O
O
OH
O
OH
CH2
O
OP
O
NH2
OH OH
O
OP
O
O
PO
O
O
CH2OP
O
O
OP
O
O
OPO
O
O
N
N
O
O
OH
O
OH
CH2
O
PO O
O
N
N
N
N
O
NH2
OH
CH2OP
O
O
OP
O
O
OPO
O
O
OHP
O
O
OPO
O
O
O
Ribonucleotides Nucleic
Acids
Dinucleotide
Combinations
e.g.
Glycoproteins
Glycolipids
Macromolecules are composed ofpolymers of a few simple
precursor molecules
Structural Diversity
Proteins
aa1aa2aa3!aan
Number of structures = 20n
~100 amino acids per molecule
20100molecules
Nucleic Acids
N1N2N3!Nn
Number of structures = 4n
1,000,000 nucleotides per DNA molecule
41,000,000molecules!!!
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PolysaccharidesHomopolymers and Heteropolymers
Many different sugar molecules
Linear and branched
Many different molecules!!!
Lipids
Many complex molecules!!!
Simple construction provides animmense number of possiblestructures fully capable of
providing the necessary diversityrequired for life.
Thermodynamic Principles
A Review
Thermodynamics
Energy and Its Effects onMatter
Thermodynamic Principles
Thermodynamics determines whethera physical process is possible (i.e.
spontaneous)
Themodynamics provides noinformation about the rate of aphysical 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 ofThermodynamics
First Law of Thermodynamics
Energy is Conserved
Second Law of Thermodynamics
The Universe Tends TowardMaximum Disorder
Consequences of Second Law ofThermodynamics
Spontaneous processes proceed indirections that increase the overalldisorder of the universe
Increased order in a system requiresdecreased 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 = GB GA
!G = !H T!S
Change in Gibbs Free Energy (!G)
Exergonic: spontaneous
Endergonic: requires input of energy
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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 Progressand
Thermodynamics
Time Course of Reaction
Time
A or B
B
Equilibrium
t1/2 (half-life)
A > B
Transition State
Br
H
H
HO C
H
Br
H
HO C
H
H
CH3Br + OH CH3OH +
Br
OH- + + Br-
Reactants "Transition State" Products
CH
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 + dDaA + bB
!G = !G + RT ln[C]c[D]d
[A]a[B]b
!G = !G + RT ln Keq
at equilibrium, !G = 0, and
!G = RT ln Keq
Standard Free Energy Changes(Standard State Conventions)
One Molar25C
1 Atmosphere
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Standard State Conventions in
Biochemistry
[H2O] = 1(actual value = 55.5 M incorporated into Keq)
[H+] = 107M (pH = 7)
Coupled Reactions
Additivity of Free EnergyChanges
Coupled Reactions
!Go
(kJ/mol)
Fructose-6-P + Pi > Fructose-1,6-bisP + H2O 13.3
ATP + H2O > ADP + P i -30.5
Fructose-6-P + ATP > Fructose-1,6-bisP + ADP -17.2