Biochemistry I

Objectives of the course (preferably expressed in terms of learning outcomes and competences): Introduction to the basic principles of Biochemistry. Structure and function of biomolecules, Metabolism and Energy, Regulation and Bioenergetics.

·    The Foundations of Biochemistry

-Cells Are the Structural and Functional Units of All Living Organisms

-Cellular Dimensions Are Limited by Diffusion

-There Are Three Distinct Domains of Life

-Escherichia coli is the Most-Studied Bacterium

-Eukaryotic Cells Have a Variety of Membranous Organelles, Which Can Be Isolated for Study

-The Cytoplasm Is Organized by the Cytoskeleton and Is Highly Dynamic

-Cells Build Supramolecular Structures

-In Vitro Studies May Overlook Important Interactions among Molecules

·    Water

Weak Interaction in Aqueous systems

-Hydrogen Bonding Gives Water its Unusual Properties

-Water Forms Hydrogen Bonds with Polar Solutes

-Water Interacts Electrostatically with Charged Solutes

-Entropy Increases as Crystalline Substances Dissolve

-Nonpolar Gases Are Poorly Soluble in Water

-Nonpolar Compounds Force Energetically Unfavorable Changes in the Structure of Water

-van der Waals Interactions Are Weak Interatomic Attractions

-Weak Interactions Are Crucial to Macromolecular Structure and Function

-Solutes Affect the Colligative Properties of Aqueous Solutions

Lionization of Water, Weak Acids and Weak Bases

-Pure Water Is Slightly Ionized

-The Ionization of Water Is Expressed by an Equilibrium Constant

-The pH Scale Designates the H+ and OH- Concentrations

-Weak Acids and Bases Have Characteristic Acid Dissociation Constants

-Titration Curves reveal the pK of Weak Acids

Buffering against pH Changes in Biological Systems

-Buffers Are Mixtures of Weak Acids and Their Conjugate Bases

-The Henderson-Hasselbalch Equation Relates pH, pKa, and Buffer Concentration

-Weak Acids or Bases Buffer Cells and Tissues against pH Changes

-Untreated Diabetes Produces Life-Threatening Acidosis

·    Amino Acids, peptides and Proteins

Amino Acids

-Amino Acids Share Common Structural Features

-The Amino Acid Residues in Proteins are L Stereoisomers

-Amino Acids Can Be Classified by R Group

-Uncommon Amino Acids Also Have Important Functions

-Amino Acids Can Act as Acids and Bases

-Amino Acids Have Characteristic Titration Curves

-Titration Curves Predict the Electric Charge of Amino Acids

-Amino Acids Differ in Their Acid-Base Properties

Peptides and proteins

-Peptides Are Chains of Amino Acids

-Peptides Can Be Distinguished by Their Ionization Behavior

-Biologically Active Peptides and Polypeptides occur in a vast range of Sizes and Compositions

-Some Proteins Contain Chemical Groups Other Than Amino Acids

Working with Proteins

-Proteins Can Be Separated and Purified

-Proteins Can Be Separated and Characterized by Electrophoresis

-Unseparated Proteins Can Be Quantified

The Structure of Proteins: Primary Structure

-The Function of a Protein Depends on Its Amino Acid Sequence

-The Amino Acid Sequences of Millions of Proteins Have Been Determined

-Short Polypeptides Are Sequenced with Automated Procedures

-Large Proteins Must Be Sequenced in Smaller Segments

-Amino Acid Sequences Can Also Be Deduced by Other Methods

-Mass Spectrometry

-Small Peptides and Proteins Can Be Chemically Synthesized

-Amino Acid Sequences Provide Important Biochemical Information

-Protein Sequences Can Elucidate the History of Life on Earth

0verview of Protein Structure

-A Protein's Conformation Is Stabilized Largely by Weak Interactions

-The Peptide Bond Is Rigid and Planar

Protein secondary Structure

-The a Helix Is a Common Protein Secondary Structure

-Amino Acid Sequence Affects Stability of the a Helix

-The B Conformation Organizes Polypeptide Chains into Sheets

-B Turns Are Common in Proteins

-Common Secondary Structures Have Characteristic Dihedral Angles

-Common Secondary Structures Can Be Assessed by Circular Dichroism

Protein Tertiary and Quaternary structures

-Fibrous Proteins Are Adapted for a Structural Function

·    Enzymes

An introduction to Enzymes

-Most Enzymes Are Proteins

-Enzymes are classified by the Reactions they Catalyze

How Enzymes Work

-Enzymes Affect reaction rates, Not Equilibria

-Reaction Rates and Equilibria have Precise Thermodynamic Definitions

-A Few Principles Explain the Catalytic Power and Specificity of Enzymes

-Weak Interactions between Enzyme and Substrate Are Optimized in the Transition State

-Binding Energy Contributes to Reaction Specificity and Catalysis

-Specific Catalytic Groups Contribute to Catalysis

Enzyme Kinetics as an Approach to Understanding Mechanism

-Substrate Concentration Affects the Rate of Enzyme-Catalyzed Reactions

-The Relationship between Substrate Concentration and Reaction Rate Can Be Expressed

  Quantitatively

·    Carbohydrates and Glycobiology

Monosaccharides and Disaccharides

-The two families of Monosaccharides are Aldoses and Ketoses

-Monosaccharides have Assymetric Centers

-The Common Monosaccharides have Cyclic Structures

-Organisms Contain a Variety of Hexose Derivatives

-Monosaccharides are Reducing Agents

-Disaccharides Contain a Glycosidic Bond

Polysaccharides

Some Homopolysaccharides are Stored Forms of Fuel

Some Homopolysaccharides serve Structural Roles

Steric Factors and Hydrogen Bonding Influence Homopolysaccharide Folding

Bacterial and Algal Cell Walls Contain Structural Heteropolysaccharides

Glycosaminoglycans are Heteropolysaccharides of the Extracellular Matrix

Glycoconjugates: Ptoteoglycans, Glycoproteins and Glycolopids

-Proteoglycans are Glycosaminoglycan-Containing Macromolecules of the Cell Surface and   

 Extracellular Matrix

-Glycoproteins Have Covalently Attached Oligosaccharides

-Glycolipids and Lipopolysaccharides are Membrane Components

Carbohydrates as Informational Molecules: The Sugar code

-Lectins Are Proteins That Read the Sugar Code and Mediate Many Biological Processes

-Lectin-Carbohydrate Interactions Are Highly Specific and Often Polyvalent

·    Nucleotides and Nucleic Acids

Some Basics

-Nucleotides and Nucleic Acids Have Characteristic Bases and Pentoses

-Phosphodiester bonds Link Successive Nucleotides in Nucleic Acids

The Properties of Nucleotide Bases Affect the Three-Dimensional structure of Nucleic Acids

Nucleic Acid Structure

-DNA Is a Double Helix that Stores Genetic Information

-DNA Can Occur in Different Three-Dimensional Forms

-Certain DNA Sequences adopt Unusual Structures

-Messenger RNAs Code for Polypeptide Chains

-Many RNAs Have More Complex Three-Dimensional Structures

Nucleic Acid Chemistry

-Double-Helical DNA and RNA Can Be Denatured

-Nucleic Acids from Different Species Can Form Hybrids

-Nucleotides and Nucleic Acids Undergo Non-enzymatic Transformations

-Some Bases of DNA Are Methylated

-The Sequences of Long DNA Strands Can Be Determined

-The Chemical Synthesis of DNA Has Been Automated

Other Functions of Nucleotides

-Nucleotides Carry Chemical Energy in Cells

-Adenine Nucleotides Are Components of Many Enzyme Cofactors

-Some Nucleotides Are Regulatory Molecules

·    DNA-Based Information Technologies

DNA Cloning: The Basics

-Restriction Endonucleases and DNA Ligase Yield Recombinant DNA

-Cloning Vectors Allow Amplification of Inserted DNA Segments

-Specific DNA Sequences Are Detectable by Hybridization

-Expression of Cloned Genes Produces Large Quantities of Protein

-Alterations in Cloned Genes Produce Modified Proteins

-Terminal Tags Provide Binding Sites for Affinity Purification

From Genes to Genomes

-DNA Libraries Provide Specialized Catalogs of Genetic Information

-The Polymerase Chain Reaction Amplifies Specific DNA Sequences

-Genome Sequences Provide the Ultimate Genetic Libraries

From Genomes to Proteomes

-Sequence or Structural Relationships Provide Information on Protein Function

-Cellular Expression Patterns Can Reveal the Cellular Function of a Gene

-Detection of Protein-Protein Interactions Helps to Define Cellular and Molecular Function

Genome Alterations and New Products of Biotechnology

-A Bacterial Plant Parasite Aids Cloning in Plants

-Manipulation of Animal Cell Genomes Provides Information on Chromosome Structure and

  Gene Expression

-New Technologies Promise to Expedite the Discovery of New Pharmaceuticals

-Recombinant DNA Technology Yields New Products and Challenges

BIOENERGETICS AND METABOLISM

·    Bioenergetics and Biochemical Reaction Types

Bioenergetics and Thermodynamics

-Biological Energy Transformations Obey the Laws of Thermodynamics

-Cells Require Sources of Free Energy

-Standard Free-Energy Change Is Directly Related to the Equilibrium Constant

-Actual Free-Energy Changes Depend on Reactant and Product Concentrations

-Standard Free-Energy Changes Are Additive

Chemical Logic and Common Biochemical Reactions

-Biochemical and Chemical Equations Are Not Identical

Phosphoryl Group Transfers and ATP

-The Free-Energy Change for ATP Hydrolysis Is Large and Negative

-Other Phosphorylated Compounds and Thioesters also have large Free Energies of Hydrolysis

-ATP Provides Energy by Group Ttansfers, Not by Simple Hydrolysis

-ATP Donates Phosphoryl, Pyrophosphoryl and Adenylyl Groups

-Assembly of Informational Macromolecules Requires Energy

·    Glycolysis, Gluconeogenesis and the Pentose Phosphate Pathway

Glycolysis

-An Overview: Glycolysis Has Two Phases

-The Preparatory Phase of Glycolysis Requires ATP

-The Payoff Phase of Glycolysis Yields ATP and NADH

-The Overall Balance Sheet Shows a Net Gain of ATP

-Glycolysis Is under Tight Regulation

Feeder Pathways for Glycolysis

-Dietary Polysaccharides and Disaccharides Undergo Hydrolysis to Monosaccharides

-Endogenous Glycogen and Starch Are Degraded by Phosphorolysis

-Other Monosaccharides enter the Glycolytic Pathway at Several Points

Fates of Pyruvate under Anaerobic Conditions: Fermentation

-Pyruvate Is the Terminal Electron Acceptor in Lactic Acid Fermentation

-Ethanol Is the Reduced Product in Ethanol Fermentation

-Fermentations Are Used to Produce Some Common Foods and Industrial Chemicals

Gluconeogenesis

-Conversion of Pyruvate to Phosphoenolpyruvate Requires two Exergonic Reactions

-Conversion of Fructose1,6-Bisphosphate to Fructose 6-Phosphate Is the Second bypass

-Conversion of Glucose 6-Phosphate to Glucose Is the Third Bypass

-Gluconeogenesis is Energetically Expensive, but Essential

-Citric Acid Cycle Intermediates and Some Amino Acids Are Glucogenic

-Mammals Cannot Convert Fatty Acids to Glucose

-Glycolysis and Gluconeogenesis are Reciprocally Regulated

Pentose Phosphate Pathway of Glucose Oxidation

-The Oxidative Phase Produces Pentose Phosphates and NADPH

-The Nonooxidative Phase Recycles Pentose Phosphates to Glucose 6-Phosphate

-Wernicke-Korsakoff syndrome is Exacerbated by a Defect in Ttansketolase

-Glucose 6-Phosphate Is Partitioned between Glycolysis and the Pentose Phosphate Pathway

·    The Citric Acid Cycle

Production of Acetyl-CoA (Activated Acetate)

-Pyruvate Is Oxidized to Acetyl-CoA and CO2

-The Pyruvate Dehydrogenase Complex requires Five Coenzymes

-The Pyruvate Dehydrogenase Complex Consists of Three Distinct Enzymes

-In Substrate Channeling, Intermediates Never Leave the Enzyme Surface

Reactions of the Citric Acid cycle

-The Citric Acid Cycle Has Eight Steps

-The Energy of Oxidations in the Cycle Is Efficiently Conserved

-Why Is the Oxidation of Acetate So Complicated?

-Citric Acid Cycle Components Are Important Biosynthetic Intermediates

-Anaplerotic Reactions Replenish Citric Acid Cycle Intermediates

Regulation of the Citric Acid

-Production of Acetyl-CoA by the Pyruvate Dehydrogenase Complex is regulated by Allosteric   

  and Covalent Mechanisms

-The Citric Acid Cycle Is Regulated at Its Three Exergonic Steps

-Substrate Channeling through Multienzyme complexes May Occur in the Citric Acid Cycle

-Some Mutations in Enzymes of the Citric Acid Cycle Lead to Cancer