1 | The Foundations of

Biochemistry

© 2017 W. H. Freeman and Company

 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)
 CHAPTER 1
The 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
 Biochemistry Is
the Chemistry of Living Matter
Living matter is characterized by:
• a high degree of complexity and organization
• the extraction, transformation, and systematic use of
energy to create and maintain structures and to do
work
• the interactions of individual components being
dynamic and coordinated
• the ability to sense and respond to changes in
surroundings
• a capacity for fairly precise self-replication while
allowing enough change for evolution
Complexity and Organization
Living Organisms Must Intake and Transform
Nutrients into Energy
Living Organisms Must
Accurately Reproduce
Three Distinct Domains of Life Defined by Cellular
and Molecular Differences That Evolved over Time
 Six Kingdoms of Life Defined by
Organism, Cellular, and Molecular Differences

Six kingdoms Cellular organization

• Archaea Unicellular prokaryote
• Bacteria Unicellular prokaryote
• Protista Unicellular eukaryote
• Fungi Uni- or Multicellular eukaryote
• Plantae Multicellular eukaryote
• Animalia Multicellular eukaryote
 Cell: The Universal Building Block
• Living organisms are made of cells.
• The simplest living organisms are unicellular (single-
celled).
• Larger organisms are multicellular (many-celled),
with different functions for different cells.
• Cells have some common features but can contain
unique components for different organisms.
All Cells Share Some Common Features
Bacterial Cell Structure
 Components of Bacterial Cell

Structure Composition Function

Cell wall Carbohydrate + protein 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
 Eukaryote Cells: More Complexity

• Have membrane-bound nucleus by definition:

– protection for DNA; site of DNA metabolism
– selective import and export via nuclear membrane pores
• Have membrane-enclosed organelles:
– mitochondria for energy in animals, plants, and fungi
– chloroplasts for energy in plant
– lysosomes for digestion of un-needed molecules
• Compartmental segregation of energy-yielding and
energy-consuming reactions helps cells to maintain
homeostasis and stay away from equilibrium.
 Animal and Plant Cells
Contain Unique Components
 Animal and Plant Cells
Contain Unique Components
 Animal and Plant Cells
Contain Identical and Unique Components

Plant Both Animal

Chloroplast
Membrane
Vacuole Nucleus and Nucleolus Lysosome
Mitochondria
Glyoxysome Rough and Smooth ER Peroxisomes
Ribosomes
Plasmodesma Golgi
Cytoskeleton
Cell wall
 Cytoplasm and Cytoskeleton
• Cytoplasm is a highly viscous solution where many
reactions take place.
• Cytoskeleton consists of microtubules, actin
filaments, and intermediate filaments.
– cellular shape and division
– intracellular organization
– intracellular transport paths
– cellular mobility
 The Cytosol Is Very Crowded

Folded proteins

Translated peptide
Cytoskeleton Maintains
Cellular Organization
 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
• the 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
The Molecular Hierarchy of Structure
Biochemistry: Unique Role of Carbon
 30 Elements Essential for Life
• Other than carbon, elements H, O, N, P, and S are also common.
• Metal ions (e.g., K+, Na+, Ca++, Mg++, Zn++, Fe++) play important roles in
metabolism.
Common Functional Groups of Biological Molecules
Biological Molecules Typically Have
Several Functional Groups
The ABCs of Life
 The Function of Molecules Strongly
Depends on Three-Dimensional Structure
• Stereoisomers
• have different physical properties
• Geometric isomers (cis vs. trans)
• have different physical and chemical properties
• Enantiomers (mirror images)
• have identical physical properties (except with regard
to polarized light) and react identically with achiral
reagents
• Diastereomers
• have different physical and chemical properties
Cis vs. Trans
Cis vs. Trans
Enantiomers and Diastereomers
Diastereomers (non-mirror images)
Enantiomers and Diastereomers
 Interactions Between
Biomolecules Are Specific
• Macromolecules fold into 3D structures with
unique binding pockets.
• Only certain molecules fit in well and can bind.
• Binding of chiral biomolecules is stereospecific.
 Interactions Between
Biomolecules Are Specific
Organisms Perform Energy Transductions to
Accomplish Work to Stay Alive

• Living organisms exist in a dynamic steady state

and are never at equilibrium with their
surroundings.
• Energy coupling allows living organisms to
transform matter into energy.
• Biological catalysts reduce energy requirement for
reactions while offering specificity.
• As the entropy of the universe increases, creating
and maintaining order requires work and energy.
 How to Speed Reactions Up
Higher temperatures
− stability of macromolecules is limiting

Higher concentration of reactants

− costly, as more valuable starting material is needed

Changing the reaction by coupling to a fast one

− universally used by living organisms

Lower activation barrier by catalysis

− universally used by living organisms
 Unfavorable and Favorable Reactions

• Synthesis of complex molecules and many other metabolic

reactions requires energy (endergonic).
– A reaction might be thermodynamically unfavorable (G°> 0).
• Creating order requires work and energy.
– A metabolic reaction might have too high an energy barrier (G‡ > 0).
• Metabolite is kinetically stable.
• The breakdown of some metabolites releases a significant
amount of energy (exergonic).
– Such metabolites (ATP, NADH, NADPH) can be synthesized using the energy
from sunlight and fuels.
– Their cellular concentration is far higher than their equilibrium
concentration.
 Energy Coupling
• Chemical coupling of exergonic and endergonic
reactions allows otherwise unfavorable reactions.
• The “high-energy” molecule (ATP) reacts directly with
the metabolite that needs “activation.”
 Catalysis
• A catalyst is a compound that increases the rate of a
chemical reaction.
• Catalysts lower the activation free energy G‡.
• Catalysts do not alter G°.
• Enzymatic catalysis offers:
– acceleration under mild conditions
– high specificity
– possibility for regulation
Enzymes Lower the Activation Energy to Increase
the Reaction Rate
Series of Related Enzymatically Catalyzed
Reactions Forms a Pathway

Metabolic pathway
• produces energy or valuable materials

Signal transduction pathway

• transmits information
Pathways Are Controlled in Order to
Regulate Levels of Metabolites

Example of a negative regulation:

Product of enzyme 5 inhibits enzyme 1 to prevent
wasteful excess products.
The Central “Dogma” of Biochemistry:
DNA → RNA → Protein
 Chapter 1: Summary
In this chapter, we learned to:

• understand what defines living organisms

• relate structure and function of the cell
• realize that the structure of biomolecules
often gives them specific functions
• grasp principles of bioenergetics
• review the forces behind evolution