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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
• Archaea
• Bacteria
• Protista
• Fungi
• Plantae
• Animalia
Cellular organization
Unicellular prokaryote
Unicellular prokaryote
Unicellular eukaryote
Uni- or Multicellular eukaryote
Multicellular eukaryote
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
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
Components of Bacterial Cell
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
Membrane
Nucleus and Nucleolus
Mitochondria
Rough and Smooth ER
Ribosomes
Golgi
Cytoskeleton
Lysosome
Peroxisomes
Chloroplast
Vacuole
Glyoxysome
Plasmodesma
Cell wall
Plant Both Animal
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
Translated peptide
Folded proteins
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
• 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
The Function of Molecules Strongly
Depends on Three-Dimensional Structure
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
Metabolic pathway
• produces energy or valuable materials
Signal transduction pathway
• transmits information
Series of Related Enzymatically Catalyzed
Reactions Forms a Pathway
Example of a negative regulation:
Product of enzyme 5 inhibits enzyme 1 to prevent
wasteful excess products.
Pathways Are Controlled in Order to
Regulate Levels of Metabolites
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

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Lehninger_Ch1_Introduction.ppt

  • 1. 1 | The Foundations of Biochemistry © 2017 W. H. Freeman and Company
  • 2. 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)
  • 3.
  • 4. 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
  • 5. 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
  • 7. Living Organisms Must Intake and Transform Nutrients into Energy
  • 9. Three Distinct Domains of Life Defined by Cellular and Molecular Differences That Evolved over Time
  • 10. Six Kingdoms of Life Defined by Organism, Cellular, and Molecular Differences Six kingdoms • Archaea • Bacteria • Protista • Fungi • Plantae • Animalia Cellular organization Unicellular prokaryote Unicellular prokaryote Unicellular eukaryote Uni- or Multicellular eukaryote Multicellular eukaryote Multicellular eukaryote
  • 11. 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.
  • 12. All Cells Share Some Common Features
  • 14. 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 Components of Bacterial Cell
  • 15. 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.
  • 16. Animal and Plant Cells Contain Unique Components
  • 17. Animal and Plant Cells Contain Unique Components
  • 18. Animal and Plant Cells Contain Identical and Unique Components Membrane Nucleus and Nucleolus Mitochondria Rough and Smooth ER Ribosomes Golgi Cytoskeleton Lysosome Peroxisomes Chloroplast Vacuole Glyoxysome Plasmodesma Cell wall Plant Both Animal
  • 19. 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
  • 20. The Cytosol Is Very Crowded Translated peptide Folded proteins
  • 22. 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
  • 23. The Molecular Hierarchy of Structure
  • 25. 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.
  • 26. Common Functional Groups of Biological Molecules
  • 27. Biological Molecules Typically Have Several Functional Groups
  • 28. The ABCs of Life
  • 29. • 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 The Function of Molecules Strongly Depends on Three-Dimensional Structure
  • 34. 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.
  • 36. 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.
  • 37. 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
  • 38. 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.
  • 39. 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.”
  • 40. 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
  • 41. Enzymes Lower the Activation Energy to Increase the Reaction Rate
  • 42. Metabolic pathway • produces energy or valuable materials Signal transduction pathway • transmits information Series of Related Enzymatically Catalyzed Reactions Forms a Pathway
  • 43. Example of a negative regulation: Product of enzyme 5 inhibits enzyme 1 to prevent wasteful excess products. Pathways Are Controlled in Order to Regulate Levels of Metabolites
  • 44. The Central “Dogma” of Biochemistry: DNA → RNA → Protein
  • 45. 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