biochemistry lecture slides week 1

8/11/2019 Biochemistry Lecture Slides Week 1

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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

biochemistry lecture slides week 1

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