1 | Foundations of Biochemistry

© 2013 W. H. Freeman and Company

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 Albert Lehninger (1917–1986)

● Citric acid cycle occurs in mitochondria

● Mechanism of oxidative phosphorylation
● Mitochondrial structure and function
● Bioenergetics

● Author of classic textbooks:

• Biochemistry (1970–1983)

• The Mitochondrion (1964)

• Bioenergetics (1965–1974)

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 CHAPTER 1
Foundations of Biochemistry
Learning goals:
• Distinguishing features of living organisms
• Structure and function of the parts of the cell
• Roles of small and large biomolecules
• Energy transformation in living organisms
• Regulation of metabolism and catalysis
• Coding of genetic information in DNA
• Role of mutations and selection in evolution
•How weak acids and bases behave in water
•How buffers work and why we need them
•How water participates in biochemical reactions
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 Biochemistry is
the Chemistry of Living Matter
Living Matter is characterized by:
• High degree of complexity and organization
• Extraction, transformation, and systematic use of
energy to create and maintain structures and to do
work
• Interactions of individual components are dynamic
and coordinated
• Ability to sense and respond to changes in
surrounding
• A capacity for fairly precise self-replication while
allowing enough change for evolution
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Complexity and Organization

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Living organisms must intake nutrients

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Living organisms must
accurately reproduce

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 Cell: The Universal Building Block
• Living organisms are made of cells
• Simplest living organisms are single-celled
• Larger organisms consist of many cells with different
functions
• Not all of the cells are the same

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 Cell: The Universal Building Block
Stem cell

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 Cell: The Universal Building Block
Bone cell

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 Cell: The Universal Building Block
Blood cell

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 Cell: The Universal Building Block
Muscle cell

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 Cell: The Universal Building Block
Fat cell

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 Cell: The Universal Building Block
Skin cell

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 Cell: The Universal Building Block
Nerve cell

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All cells share some common features

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Bacterial, animal, and plant cells are different

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 Components of Bacterial Cell

Structure Composition Function

Cell wall Peptidoglycan Mechanical support
Cell membrane Lipid + protein Permeability barrier
Nucleoid DNA + protein Genetic information
Ribosomes RNA + protein Protein synthesis
Pili Protein Adhesion, conjugation
Flagella Protein Motility
Cytoplasm Aqueous solution Site of metabolism

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Bacterial, animal, and plant cells
are different

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Bacterial, animal, and plant cells
are different

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 Biochemistry is
the Chemistry of Living Matter
• The basis of all life is the chemical reactions that take place
within the cell.

Chemistry allows for:

• A high degree of complexity and organization
• Extraction, transformation, and systematic use of energy to
create and maintain structures and to do work
• The interactions of individual components to be dynamic and
coordinated.
• The ability to sense and respond to changes in surrounding
• A capacity for fairly precise self-replication while allowing
enough change for evolution

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Organisms can also be classified by:
different energy and carbon sources

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 Living systems extract energy

• From sunlight
– plants
– green bacteria
– cyanobacteria
• From fuels
– animals
– most bacteria

• Energy input is needed in order to maintain life 24

 The Molecular Logic of Life

We look at the chemistry that is behind:

• Accelerating reactions
• Organization of metabolism and signaling
• Storage and transfer of information

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The ABCs of Life

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The Molecular Hierarchy of Structure

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Biochemistry: Unique Role of Carbon

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 30 Elements Essential for Life
• Other than carbon, elements H, O, N, P, S are also common
• Metal ions (e.g., K+, Na+, Ca++, Mg++, Zn++, Fe++) play important roles
in metabolism

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Common Functional Groups of Biological Molecules

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Biological molecules typically have several
functional groups

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 Interactions between
biomolecules are specific

• Macromolecules have unique binding pockets

• Only certain molecules fit in well and can bind
• Binding of chiral biomolecules is stereospecific

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 Interactions between
biomolecules are specific

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Organisms perform energy transductions
to accomplish work to stay alive

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ATP: Chemical Currency of Energy

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Series of related enzymatically catalyzed
reactions forms a pathway

Metabolic Pathway
• produces energy or valuable materials

Signal Transduction Pathway

• transmits information

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Pathways are controlled in order to
regulate levels of metabolites

Example of a negative regulation:

Product of enzyme 5 inhibits enzyme 1
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Genetic and Evolutionary Foundations

• Life on Earth arose 3.5–3.8 billion years ago

• Formation of self-replicating molecules a key step
• Could it been DNA?
• Could it been proteins?

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 RNA World?

• RNA can act both as the information carrier and

biocatalyst

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 Complementarity in DNA allows for
replication with near-perfect fidelity

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The Central “Dogma” of Biochemistry:
DNA → RNA → Protein

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 Natural selection
favors some mutations
• Mutations occur more or less randomly
• Mutations that give organisms an advantage in a
given environment are more likely to be propagated

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 Natural selection
favors some mutations

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Evolution of Eukaryotes through
Endosymbiosis

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 What is pH?
• pH is defined as the negative
pH = -log[H+] logarithm of the hydrogen ion
concentration
• Simplifies equations
K w  [H  ][OH - ]  11014 M 2 • The pH and pOH must always
add to 14
 log[H  ]  log[OH- ]  14 • In neutral solution, [H+] = [OH–]
and the pH is 7
pH  pOH  14 • pH can be negative ([H+] = 6 M)
pH scale is logarithmic:
1 unit = 10-fold
pH of Some Common Liquids
 Dissociation of Weak Electrolytes:
Principle
O
+ H2O
Keq O • Weak electrolytes dissociate
H3C H3 C + H3O+
OH O- only partially in water.

K a  K eq  [H 2 O] • Extent of dissociation is
determined by the acid
[H  ][CH 3COO - ] dissociation constant Ka.
Ka   1.74 10 5 M
[CH 3COOH]

• We can calculate the pH if the

 [CH 3COOH] Ka is known. But some
[H ]  Ka 
[CH 3COO ] algebra is needed!
Dissociation of Weak Electrolytes:
Example
What is the final pH of a solution when 0.1 moles of
acetic acid is added to water to a final volume of 1L?
O O
H3C
Ka • We assume that the
H3 C + H+
OH O- only source of H+ is
0.1 – x x x the weak acid

[ x ][x ]
Ka   1.74 10 5 M
[0.1 - x] • To find the [H+], a
quadratic equation
x 2  1.74 10 6  1.74 10 5 x
must be solved
x 2  1.74 10 5 x  1.74 10 6  0
x = 0.001310, pH = 2.883
Dissociation of Weak Electrolytes:
Simplification

O O • The equation can be

Ka
H3C + H+
H3 C simplified if the amount of
OH O-
dissociated species is much
0.1 – x x x
0.1 x x less than the amount of
undissociated acid

Ka 
[ x ][x ]
 1.74 10 5 M • Approximation works for
[0.1] sufficiently weak acids and
x 2  1.74 10 6 bases
• Check that x < [total acid]
x = 0.00132, pH = 2.880
 pKa measures acidity
• pKa = –log Ka (strong acid  large Ka  small pKa)
 Buffers are mixtures of weak acids
and their anions (conjugate base)

• Buffers resist change in pH

•At pH = pKa, there is a 50:50 mixture of acid and

anion forms of the compound

•Buffering capacity of acid/anion system is greatest

at pH = pKa

•Buffering capacity is lost when the pH differs from

pKa by more than 1 pH unit
Acetic Acid-Acetate as a Buffer System
Weak acids have different pKas
Henderson–Hasselbalch Equation:
Derivation
[H  ][A - ]
HA 
 H+ + A- Ka 
[HA]
[HA]
[H ]  K a
+

[A - ]

[HA]
- log[H ]  -logK a  log
[A-]

-
[A ]
pH  pK a  log
[HA]
 Biological Buffer Systems
• Maintenance of intracellular pH is vital to all cells
– Enzyme-catalyzed reactions have optimal pH
– Solubility of polar molecules depends on H-bond donors and acceptors
– Equilibrium between CO2 gas and dissolved HCO3– depends on pH

• Buffer systems in vivo are mainly based on

– phosphate, concentration in millimolar range
– bicarbonate, important for blood plasma
– histidine, efficient buffer at neutral pH

• Buffer systems in vitro are often based on sulfonic acids of

cyclic amines
– HEPES HO
– PIPES N N
SO3Na
– CHES
Water as a Reactant in Biochemistry
Water bound to proteins is
essential for their function
Water bound to proteins is
essential for their function
Water bound to proteins is
essential for their function
 Chapter 1: Summary
In this chapter, we learned:
• To understand what defines living organisms
• To relate structure and function of the cell
• To realize that the structure of biomolecules
often gives them specific functions
• To grasp principles of bioenergetics
• To review the forces behind evolution
• The behavior of weak acids and bases in water
• The way water can participate in biochemical
reactions 63