1. Foundations of Biochemistry Lecture 1
© 2009 W. H. Freeman and Company

2. Albert Lehninger (1917-1986) Mechanism of oxidative phosphorylation
Citric acid cycle occurs in mitochondria
Mechanism of oxidative phosphorylation
Mitochondrial structure and function
Bioenergetics
Author of classic textbooks:
Biochemistry ( )
The Mitochondrion (1964)
Bioenergetics ( )

3. Biochemistry is a Science Dealing with the Chemistry of Living Matter
We know quite well what is chemistry
But what is living matter?
Life is characterized by
High degree of complexity
Extraction, transformation, and systematic use of energy to create and maintain structures and to do work
Ability to sense and respond to changes in surrounding
A capacity for fairly precise self-replication while allowing enough change for evolution

4. Life is Complex Living organisms have
internal structures with defined functions
large number of different compounds
macromolecules that are capable of highly specific interactions

5. Cell: The Universal Building Block
Living organisms are made of cells
Simplest living organisms are singe-celled
Larger organisms consists many cells with different functions
Not all the cells are the same

6. Three Domains of Life
Differences in cellular and molecular level define three distinct domains of life

7. Six Kingdoms of Life Six kingdoms Archaea Bacteria Protista Fungi
Alternatively, living things are placed in kingdoms on the basis of similarities and differences at the organism, cellular, and molecular levels
Six kingdoms
Cellular organization
Unicellular prokaryote
Unicellular eukaryote
Uni- or Multicellular eukaryote
Multicellular eukaryote
Archaea
Bacteria
Protista
Fungi
Plantae
Animalia

8. Bacterial, Plant, and Animal Cells are Different
The internal structure and properties of cells from organisms in different kingdoms are rather different

9. 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

10. Eukaryote Cells: More Complexity
Have nucleus by definition
protection for DNA; site of DNA metabolism
selective import and export via nuclear membrane pores
some cells become anuclear (red blood cells)
Have membrane-enclosed organelles
Mitochondria for energy in animals, plants and fungi
Chloroplasts for energy in plant
Lysosome for digestion of un-needed molecules
Spatial separation of energy-yielding and energy consuming reactions helps cells to maintain homeostasis and stay away from equilibrium

11. Components of Animal Cell

12. Cytoplasm and Cytoskeleton
Cytoplasm is highly viscous solution where many reactions take place
Cytoskeleton consists of microtubules, actin filaments, and intermediate filaments
cell shape
transport paths
movement

13. Living Systems Extract Energy
From sunlight
plants
green bacteria
cyanobacteria
From fuels
animals
most bacteria
Energy input is needed in order to maintain
complex structures and be in a dynamic steady
state, away from the equilibrium

14. 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

15. Biochemistry: Unique Role of Carbon
Biomolecules are carbon-based
Elements H, O, N, P, S are also common
Metal ions (e.g. K+, Na+, Ca++, Mg++, Zn++, Fe++) play important roles in metabolism
Together, about 30 elements are essential for life

16. Biological Molecules Typically Have Several Functional Groups

17. Structure of Biological Molecules is Important
The function of molecules strongly depend on three-dimensional structure

18. Stereoisomers have Different Biological Properties
Cis and trans isomers have also different physical and chemical properties

19. Optical Isomers have Different Biological Properties
Enantiomers have identical physical properties (except regard to polarized light) and react identically with achiral reagents.
Diastereomers have different physical and chemical

20. 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

21. How to Speed Reactions Up?
Higher temperatures
Stability of macromolecules is limiting
Higher concentration of reactants
Costly as more valuable starting material is needed
Change the reaction by coupling to a fast one
Universally used by living organisms
Lower activation barrier by catalysis

22. 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
Metabolic reaction might have too high energy barrier (G‡ > 0)
Metabolite is kinetically stable
Breakdown of some metabolites releases significant amount of energy (exergonic)
Such metabolites (ATP, NADH, NADPH) can be synthesizes using the energy from sunlight and fuels
Their cellular concentration is far higher than their equilibrium concentration.

23. ATP: Chemical Currency of Energy

24. 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”

25. Catalysis
A catalyst is a compound that increases the rate of a chemical reaction
Catalysts lower the activation free energy G‡
Catalysts does not alter G°
Catalysis offers:
Acceleration under mild conditions
High specificity
Possibility for regulation

26. 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?

27. Evolution of Eukaryotes through Endosymbiosis

28. The Central “Dogma” of Biochemistry
Pathway for the flow of genetic information:
DNA → RNA → Protein
DNA stores information
RNA transmits information
Protein function manifests
information

29. Natural Selection Favors Some Mutations
Mutations occur more or less randomly
Mutations that give organism an advantage in a given environment are more likely to be propagated