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

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 (1970-1983) The Mitochondrion (1964) Bioenergetics (1965-1974)

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

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

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

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

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

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

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

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

Components of Animal Cell

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

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

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

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

Biological Molecules Typically Have Several Functional Groups

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

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

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

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

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

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.

ATP: Chemical Currency of Energy

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 does not alter G° Catalysis offers: Acceleration under mild conditions High specificity Possibility for regulation

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?

Evolution of Eukaryotes through Endosymbiosis

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

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