Section 1 Introduction to Biochemical Principles

Section 1

Introduction to Biochemical Principles

Chapter 1

Biochemistry: An Introduction

Life: It is a Mystery!

Life: It is a Mystery! Why study biochemistry?

Foundation upon which all of the modern life sciences are built

Biology can’t be done without biochemistry

Life and its Diversity Life is Resilient

Figure 1.1 Diversity of Life

Section 1.1: What Is Life?

All Life Obeys the Same Chemical and Physical Laws: Life is complex and dynamic Life is organized and self-

sustaining Life is cellular Life is information-based Life adapts and evolves

Figure 1.3 Hierarchical Organization

Section 1.2: Biomolecules

Living organisms composed of inorganic and organic molecules

Water is the matrix of life Six principal elements: carbon, hydrogen, oxygen,

nitrogen, phosphorous, and sulfur Trace elements are also important (i.e., Na+, K+,

Mg2+, and Ca2+)


Major Classes of Small Biomolecules Many organic molecules are relatively small (less than

1000 Daltons (Da)) Families of small molecules: amino acids, sugars, fatty

acids, and nucleotides


The properties of even the simplest cells are remarkable

Autopoiesis has been coined to describe the remarkable properties of living organisms

Metabolism is defined as: The acquisition and utilization of energy Synthesis of molecules needed for cell structure

and function Growth and development Removal of waste products

Section 1.3: Is the Living Cell a Chemical Factory?

Biochemical Reactions Nucleophilic substitution Elimination Addition Isomerization Oxidation-Reduction


Energy Energy is defined as the capacity to do work Cells generate most of their energy with redox

reactions The energy captured when electrons are

transferred from an oxidizable molecule to an electron-deficient molecule is used to drive ATP synthesis

Acquiring energy from the environment happens in distinct ways:

Autotrophs Heterotrophs


Overview of Metabolism Metabolic pathways come in two

types: anabolic and catabolic Anabolic: large complex molecules

synthesized from smaller precursors Catabolic: large complex molecules

degraded into smaller, simpler products

Energy transfer pathways capture energy and transform it into a usable form

Signal transduction pathways allow cells to receive and respond to signals

Figure 1.21 A Biochemical Pathway


Figure 1.22 Anabolism and Catabolism


Biological Order The coherent unity that is observed in all

organisms: Synthesis of biomolecules Transport across membranes Cell movement Waste removal


Section 1.4: Systems Biology

Systems Biology: Living Organisms Regarded as Integrated Systems Emergence: Interaction of parts can lead to new properties

Figure 1.23 Feedback Mechanisms

Section 1.4: Systems Biology

Robustness: Many biological systems remain stable despite perturbations

Modularity: Complex systems are composed of modules

Figure 1.23 Feedback Mechanisms

Chapter 2

Living Cells

Section 2.1: Basic Themes

Understanding of the biological context of biochemical processes is enhanced by examining six key concepts:

Figure 2.2 Hydrophobic Interactions Between Water and a Nonpolar Substance


Water Unique polar structure Among its most important properties is

interaction with a wide range of substances

Figure 2.2 Hydrophobic Interactions Between Water and a Nonpolar Substance

Section 2.1: Basic ThemesBiological Membranes

Thin, flexible, and stable sheet-like structures Selective physical barrier Phospholipid bilayer with integral and peripheral membrane proteins

Figure 2.3 Membrane Structure


Figure 2.5

Biological Machines

Self-Assembly Many biomolecules spontaneously undergo self-

assembly into supermolecular structuresMolecular Machines

Many multisubunit complexes involved in cellular processes function as molecular machines


Figure 2.6

Volume Exclusion

Macromolecular Crowding The interior space within cells is dense and

crowded The excluded volume may be between 20% and

40%Signal Transduction

Reception, transduction, and response

Figure 2.7 Typical

Bacterial Cell

Prokaryotes include bacteria and archaea They have common features: cell wall, plasma

membranes, circular DNA, and no membrane-bound organelles

Section 2.2: Structure of Prokaryotic Cells


Figure 2.8

Bacterial Cell

Cell Wall The prokaryotic cell

wall is a complex semi-rigid structure primarily for support and protection

The cell wall is primarily composed of peptidoglycan


Figure 2.8 Bacterial Cell

Figure 2.9 Bacterial Plasma Membrane

Plasma Membrane Directly inside the cell wall is the plasma

membrane, a phospholipid bilayer A selectively permeable membrane that may be

involved in photosynthesis or respiration


Figure 2.10 Bacterial Cytoplasm

Cytoplasm Prokaryotic cells do have

functional compartments Nucleoid, which is centrally

located and contains the circular chromosome

Also contains small DNA plasmids

Inclusion bodies are large granules that contain organic or inorganic compounds


Figure 2.7 Typical

Bacterial Cell

Pili and Flagella Many bacteria have external appendages

Pili (pilus) are for attachment and sex Flagella (flagellum) are used for locomotion


Figure 2.11 Animal Cell

Eukaryotic cells are structurally complex Membrane-bound organelles and the endomembrane system increase surface area for chemical reactions

Section 2.3: Structure of Eukaryotic Cells

Important structures: plasma membrane, endoplasmic reticulum, Golgi apparatus, nucleus, lysosomes, mitochondria, chloroplasts, ribosomes, and the cytoskeleton


Figure 2.12 Plant Cell

Plasma Membrane Isolates the cell and is selectively permeable Outside the plasma membrane are the glycocalyx and the extracellular matrix


Figure 2.13

Plasma Membrane

Endoplasmic Reticulum The endoplasmic reticulum (ER) is a series of membranous tubules, vesicles, and flattened sacks

The internal space is the ER lumen


Figure 2.15

Endoplasmic Reticulum

Two types: Rough ER functions

include protein synthesis, folding, and glycosylation

Smooth ER functions include lipid biosynthesis and Ca2+

storage


Figure 2.15

Endoplasmic Reticulum

Golgi Apparatus The Golgi apparatus is

formed of large, flattened, sac-like membranous vesicles

Processes, packages, and distributes cell products

Has a cis and a trans face (cisternae)


Figure 2.16 The Golgi Apparatus

Cisternal maturation model vesicles are recycled back to the cis Golgi from the trans Golgi

Secretory products concentrated at the trans Golgi into secretory vesicles

Involved in exocytosis


Figure 2.17 Exocytosis

Nucleus The nucleus is the

most prominent organelle

Contains the hereditary information

Site of transcription Nuclear components:

Nucleoplasm Chromatin (genome) Nuclear matrix Nucleolus Nuclear envelope


Figure 2.18 Eukaryotic Nucleus

The nuclear envelope surrounds the nucleoplasm

The nuclear envelope has nuclear pores referred to as nuclear pore complexes

Structures through which pass most of the molecules that enter and leave the nucleus


Figure 2.19 The Nuclear Pore Complex

Vesicular Organelles The eukaryotic cell has vesicles

Vesicles originate in the ER, Golgi and/or via endocytosis


Figure 2.20 Receptor-Mediated Endocytosis

SL

COMP: Delete comma

Phagocytosis Receptor-mediated

endocytosis Endocytic cycle is used for

recycling and remodeling of membranes


Figure 2.20 Receptor-Mediated Endocytosis


Figure 2.21 Lysosomes

Vesicular Organelles Continued Lysosomes are vesicles that

contain digestive enzymes Enzymes are acid hydrolases Degrade debris in cells and

involved in autophagy


Figure 2.23 The Mitochondrion

Mitochondria The mitochondria

(mitochondrion) are recognized as the site of aerobic metabolism

Mitochondria are the principle source of cellular energy

Have inner and outer membrane surrounding the matrix

Have DNA and ribosomes


Peroxisomes The peroxisome is a small organelle containing

oxidative enzymes Detoxifies peroxides (e.g., H2O2)


Figure 2.25 Chloroplast

Plastids Plastids are organelles

found only in plants, algae, and some protists

Two types: leucoplasts and chromoplasts

Chloroplasts are chromoplasts specialized for photosynthesis


Cytoskeleton The cytoskeleton is an intricate supportive

network of fibers, filaments, and associated proteins

Three main components: Microtubules Microfilaments Intermediate filaments

Main functions includE cell shape and structure, large- and small-scale cell movement, solid-state biochemistry, and signal transduction


Figure 2.26 The Cytoskeleton


Cytoskeleton Cilia and flagella, whip-like appendages encased

in plasma membrane, are highly specialized for their roles in propulsion

Bending occurs via ATP-driven structural changes in dynein molecules


Figure 2.27 Cilia and Flagella

Chapter 3

Water: The Matrix of Life

Section 3.1: Molecular Structure of Water

Water is essential for lifeWater’s important properties include:Chemical stability Remarkable solvent propertiesRole as a biochemical reactant Hydration


Water has a tetrahedral geometry

Oxygen is more electronegative than hydrogen

Figure 3.2 Tetrahedral

Structure of Water


Figure 3.4 Water Molecule

Figure 3.3 Charges on a Water Molecule

Larger oxygen atom has partial negative charge (d-) and hydrogen atoms have partial positive charges (d+)


Bond between oxygen and hydrogen is polarWater is a dipole because the positive and negative charges are separate

Figure 3.5 Molecular Dipoles in an Electric Field


Figure 3.6 Hydrogen Bond

An electron-deficient hydrogen of one water is attracted to the unshared electrons of water forming a hydrogen bond Can occur with oxygen,

nitrogen, and fluorine Has electrostatic (i.e.,

opposite charges) and covalent (i.e., electron sharing) characteristics

Section 3.2: Noncovalent Bonding

Noncovalent interactions are electrostatic Weak individually, but play vital role in

biomolecules because of cumulative effects

Three most important noncoavalent bonds: Ionic interactionsVan der Waals forcesHydrogen bonds


Ionic Interactions Oppositely charged ions attract one another Ionized amino acid side chains can form salt bridges with one another

Biochemistry primarily investigates the interaction of charged groups on molecules, which differs from ionic interactions like those of ionic compounds (e.g., NaCl)


Figure 3.7 Tetrahedral Aggregate of Water Molecules

Hydrogen Bonds Electron-deficient hydrogen is

weakly attracted to unshared electrons of another oxygen or nitrogen

Large numbers of hydrogen bonds lead to extended network


Figure 3.8 Dipolar Interactions

Van der Waals Forces Occur between neutral,

permanent, and/or induced dipoles

Three types: Dipole-dipole

interactions Dipole-induced dipole

interactions Induced dipole-induced

dipole interactions


Water’s melting and boiling points are exceptionally high due to hydrogen bonding Each water molecule can form four hydrogen

bonds with other water molecules Extended network of hydrogen bonds

Section 3.3: Thermal Properties of Water

Maximum number of hydrogen bonds form when water has frozen into ice Open, less-dense structure


Figure 3.9 Hydrogen Bonding

Between Water Molecules in Ice

Water has an exceptionally high heat of fusion and heat of vaporization Helps to maintain an organism’s internal

temperature


Figure 3.10 Solvation Spheres

Water is the ideal biological solventHydrophilic Molecules, Cell Water Structuring, and Sol-Gel Transitions Water can dissolve ionic and polar substances Shells of water molecules form around ions

forming solvation spheres

Section 3.4: Solvent Properties of Water

Figure 3.11 Diagrammatic View of Structured Water

Structured Water Water is rarely free

flowing Water is associated

with macromolecules and other cellular components

Forms complex three- dimensional bridges between cellular components


Sol-Gel Transitions Cytoplasm has properties of a gel (colloidal

mixture) Transition from gel to sol important in cell

movement Amoeboid motion provides an example of

regulated, cellular, sol-gel transitions


Figure 3.12 Amoeboid Movement

Hydrophobic Molecules and the Hydrophobic Effect Small amounts of nonpolar substances are excluded

from the solvation network forming droplets This hydrophobic effect results from the solvent

properties of the water and is stabilized by van der Waals interactions


Figure 3.13 The Hydrophobic Effect


Figure 3.14 Formation of Micelles

Amphipathic Molecules Contain both polar and

nonpolar groups Amphipathic molecules

form micelles when mixed with water

Important feature for the formation of cellular compartments

Osmotic Pressure Osmosis is the spontaneous passage of solvent

molecules through a semipermeable membrane Osmotic pressure is the pressure required to stop

the net flow of water across the membrane Osmotic pressure depends on solute

concentration


Figure 3.15 Osmotic Pressure


Can be measured with an osmometer or calculated (=iMRT)

Cells may gain or lose water because of the environmental solute concentration

Solute concentration differences between the cell and the environment can have important consequences

Isotonic solution Hypotonic solution Hypertonic solution

Figure 3.17 Effect of Solute Concentration on Animal Cells


Proteins with ionizable amino acid side chains affect cellular osmolarity by attracting ions of opposite charge

There is asymmetry of charge across the membrane due to ions forming an electrical gradient (membrane potential)

Unlike animal cells, plant cells use osmotic pressure to drive growth via turgor pressure

Section 3.5: Ionization of Water

Water can occasionally ionize, forming a hydrogen ion (H+) and a hydroxide ion (OH-) In an aqueous solution, a proton combines with a

water molecule to form H3O+ (hydronium ion)

H2O H+ + OH- (reversible)


The ion product of water is referred to as Keq[H2O] or Kw = [H+][OH-]

Kw at 25°C and 1 atm pressure is 1.0 10-14

Kw is temperature-dependent; therefore, pH is temperature-dependent as well


Acids, Bases, and pH An acid is a proton donor A base is a proton acceptor Most organic molecules that donate or accept

protons are weak acids or weak bases A deprotonated product of a dissociation

reaction is a conjugate base


The pH scale can be used to measure hydrogen ion concentration pH=-log[H+]

Figure 3.18 The pH Scale and the pH Values of Common Fluids


pKa is used to express the strength of a weak acid Lower pKa equals a stronger

acid pKa=-logKa

Ka is the acid dissociation constant

Figure 3.18 The pH Scale and the pH Values of Common Fluids



Buffers Regulation of pH is universal and essential for all

living things Certain diseases can cause changes in pH that

can be disastrous Acidosis and Alkalosis

Buffers help maintain a relatively constant hydrogen ion concentration

Commonly composed of a weak acid and its conjugate base


Buffers Continued Establishes an

equilibrium between buffer’s components

Follows Le Chatelier’s principle

Equilibrium shifts in the direction that relieves the stress

Figure 3.19 Titration of Acetic Acid with NaOH


Henderson-Hasselbalch Equation Establishes the relationship between pH and pKa

for selecting a buffer Buffers are most effective when they are

composed of equal parts weak acid and conjugate base

Best buffering occurs 1 pH unit above and below the pKa

pH = pKa + log[A-]

[HA]

Henderson-Hasselbalch Equation


Worked Problem 3.5 (Page 91) Calculate the pH of a mixture of 0.25 M acetic acid

(CH3COOH) and 0.1 M sodium acetate (NaC2H3O2)

The pKa of acetic acid is 4.76

Solution:

pH = pKa + log[acetate]

[acetic acid]

pH = 4.76 + log[0.1]

[0.25]= 4.76 + 0.398 = 4.36


Figure 3.20 Titration of Phosphoric Acid with NaOH

Weak Acids with Multiple Ionizable Groups

Each ionizable group can have its own pKa

Protons are released in a stepwise fashion


Physiological Buffers Buffers adapted to solve specific physiological

problems within the body Bicarbonate Buffer

One of the most important buffers in the blood CO2 + H2O H+ + HCO3

- (HCO3- is bicarbonate):

This is a reversible reaction Carbonic anhydrase is the enzyme responsible


Figure 3.21 Titration of H2PO4

-

by Strong Base

Phosphate Buffer Consists of H2PO4

-/HPO42-

(weak acid/conjugate base) H2PO4

- H+ + HPO42-

Important buffer for intracellular fluids

Protein Buffer Proteins are a significant

source of buffering capacity (e.g., hemoglobin)

Chapter 4

Energy

Section 4.1: Thermodynamics

Energy is the basic constituent of the universeEnergy is the capacity to do work In living organisms, work is powered with the energy provided by ATP

Thermodynamics is the study of energy transformations that accompany physical and chemical changes in matterBioenergetics is the branch that deals with living organisms


Bioenergetics is especially important in understanding biochemical reactions These reactions are affected by three factors:

Enthalpy—total heat content Entropy—state of disorder Free Energy—energy available to do chemical

work


Three laws of thermodynamics: First Law of Thermodynamics—Energy cannot be

created nor destroyed, but can be transformed Second Law of Thermodynamics—Disorder

always increases Third Law of Thermodynamics—As the

temperature of a perfect crystalline solid approaches absolute zero, disorder approaches zero


First two laws are powerful biochemical tools

Thermodynamic transformations take place in a universe composed of a system and its surroundings

Energy exchange between a system and its surroundings can happen in two ways: heat (q) or work (w) Work is the displacement or

movement of an object by force

Figure 4.2 A Thermodynamic Universe


First Law of Thermodynamics Expresses the relationship between internal

energy (E) in a closed system and heat (q) and work (w)

Total energy of a closed system (e.g., our universe) is constant

DE = q + w Unlike a human body, which is an open

system Enthalpy (H) is related to internal energy by the

equation: H = E + PV DH is often equal to DE (DH = DE)


First Law of Thermodynamics Continued If DH is negative (DH <0) the reaction gives off

heat: exothermic If is DH positive (DH >0) the reaction takes in

heat from its surroundings: endothermic In isothermic reactions (DH =0) no heat is

exchanged Reaction enthalpy can also be calculated:

DHreaction = SDHproducts SDHreactants

Standard enthalpy of formation per mole (25°C, 1 atm) is symbolized by DHf°


Second Law of Thermodynamics Physical or chemical changes resulting in a

release of energy are spontaneous Nonspontaneous reactions require constant

energy input

Figure 4.3 A Living Cell as a Thermodynamic System


As a result of spontaneous processes, matter and energy become more disorganized

Gasoline combustion The degree of disorder is

measured by the state function entropy (S)

Figure 4.4 Gasoline Combustion


Second Law of Thermodynamics Continued Entropy change for the universe is positive for

every spontaneous process DSuniv = DSsys + DSsurr

Living systems do not increase internal disorder; they increase the entropy of their surroundings

For example, food consumed by animals to provide energy and structural materials needed are converted to disordered waste products (i.e., CO2, H2O and heat)

Organisms with a DSuniv = 0 or equilibrium are dead

Section 4.2: Free Energy

Free energy is the most definitive way to predict spontaneity

Gibbs free energy change or DG Negative DG indicates

spontaneous and exergonic Positive DG indicates

nonspontaneous and endergonic

When DG is zero, it indicates a process at equilibrium

Figure 4.5 The Gibbs Free Energy Equation


Standard Free Energy Changes Standard free energy, DG°, is defined for

reactions at 25°C,1 atm, and 1.0 M concentration of solutes

Standard free energy change is related to the reactions equilibrium constant, Keq

DG° = -RT ln Keq

Allows calculation of DG° if Keq is known Because most biochemical reactions take place at

or near pH 7.0 ([H+] = 1.0 10-7 M), this exception can be made in the 1.0 M solute rule in bioenergetics

The free energy change is expressed as DG°′

Coupled Reactions Many reactions have a positive DG°′ Free energy values are additive in a reaction

sequence If a net DG°′ is sufficiently negative, forming the

product(s) is an exergonic process

Figure 4.6 A Coupled Reaction



The Hydrophobic Effect Revisited Understanding the spontaneous aggregation of

nonpolar substances is enhanced by understanding thermodynamic principles

The aggregation decreases the surface area of their contact with water, increasing its entropy

The free energy of the process is negative; therefore, it proceeds spontaneously

Spontaneous exclusion of water is important in membrane formation and protein folding

Adenosine triphosphate is a nucleotide that plays an extraordinarily important role in living cells

Hydrolysis of ATP ADP + Pi provides free energy

Figure 4.7 Hydrolysis of ATP

Section 4.3: The Role of ATP

Drives reactions of several types:

1. Biosynthesis of biomolecules 2. Active transport across membranes 3. Mechanical work such as muscle contraction

Figure 4.8 The Role of ATP


Structure of ATP is ideally suited for its role as universal energy currency Its two terminal phosphoryl groups are linked by phosphoanhydride bonds

Specific enzymes facilitate ATP hydrolysis

Figure 4.9 Structure of ATP


The tendency of ATP to undergo hydrolysis is an example of its phosphoryl group transfer potential ATP acts as energy currency, because it can carry

phosphoryl groups from high-energy compounds to low-energy compounds

Figure 4.10 Transfer of Phosphoryl Groups



Several factors need to be considered to understand why ATP is so exergonic:

1. At physiological pH, ATP has multiple negative charges2. Because of resonance stabilization, the products of ATP hydrolysis are more stable than resonance-restricted ATP

Resonance is when a molecule has two or more alternative structures that differ only in the position of their electrons

3. Hydrolysis products of ATP are more easily solvated4. Increase in disorder with more molecules

Figure 4.11 Contributing Structure of the Resonance Hybrid of Phosphate


Documents

Section 1 Introduction to Biochemical Principles