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Chap
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3-25
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1 Appendix section & sections concerning cell biology in the textbook
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I
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The ultimate goal of biochemistry is to explain all life processes in molecular detail
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It is of no
surprise that the first "biochemists" actually were organic chemists who specialized in the
chemistry of compounds derived from living organisms
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Research endeavors such as the
human genome project ultimately owe their success to basic discoveries about the structure of
the DNA "double helix" by Watson & Crick and the development of DNA sequencing methods
by Fredrick Sanger
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The chemical basis of life
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Carbon is the third most abundant element in living organisms (relative abundance
H > O > C > N > P > S)
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1
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shows the 29 elements found in living organisms
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The properties of biomolecules, such as shape
and chemical reactivity, are best described by the discipline of organic chemistry
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Representations of molecular structures
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Therefore, you must be familiar with each of these types of representations
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Space-filling models show van der Waals radii of the atoms in molecules, i
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, the surfaces of
closest possible approach by neighboring molecules
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Chemical bonding
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sp3 and sp2
molecular orbitals are the most prevalent in biomolecules
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C
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The chemical reactions of biomolecules are dictated by the functional groups they
contain
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1
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shows the general formulas of common organic compounds and functional
groups that will be encountered constantly in the proteins, carbohydrates, nucleic acids and
simple metabolites you will study
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III
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The principle biomolecules in cells (proteins, polysaccharides, and nucleic acids) are
polymer chains of amino acids, monosaccharides, and nucleotides, respectively
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Each monomer unit of a biopolymer is referred to as a residue
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Proteins
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Proteins also are the
major structural components of most cells and tissues
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1
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Peptide bonds actually are amide bonds which are formed by the condensation of the
carboxyl groups and amino groups of consecutive amino acids in the polymer chain
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Projecting
out from the backbone are the R-groups which are the side-chains of the amino acids
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e
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The enzymes comprise one subclass of proteins
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Specificity is achieved because the binding site for reactants--the active site--is highly
complementary in shape to the reactants and products
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1
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This enzyme binds to and cleaves the polysaccharide portion of
the bacterial cell wall
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Lysozyme is
present in tears and egg whites where it helps protect against unwanted bacterial growth and
infection
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Many of
these proteins and enzymes are the targets of poisons and drugs whose actions also will be
discussed
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Polysaccharides
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g
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Different polysaccharides perform either structural (cellulose) or energy storage
(glycogen, starch) functions
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You should be familiar with the different
types of representations used to describe the structures of monosaccharides (Fig
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5)
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Namely, the structure of the glycosidic bonds linking
the glucose units in cellulose and starch are very similar, yet the subtle difference in bond
configuration determines whether the polymer is digestible (starch) or not (cellulose)
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The
medical relevance of these topics cannot be overemphasized
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C
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Nucleic acids are composed of nucleotide monomer units
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1
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The nucleotide ATP is the major energy currency of the cell which is used to power a huge
variety of energy-requiring reactions
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Deoxyribonucleotides (containing deoxyribose) make up DNA
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1
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Nucleotides play key roles in
information transfer in all organisms (DNA → RNA → protein)
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For example, the formation of peptide bonds during protein
synthesis actually is performed by one of the RNA constituents of the ribosome
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Lastly, a number of nucleic acid analogs are
used to inhibit DNA synthesis and are extremely important in management of cancers and virally
caused diseases such as AIDS
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Lipids and membranes
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e
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Lipids contain relatively few polar functional groups
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The primary building block of many
lipids is a fatty acid
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1
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12)
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1
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Biological membranes usually contain proteins, and protein content and
composition is highly variable and determined by membrane function
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In later chapters, we
will cover the functions of membrane-bound proteins, enzymes and receptors
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IV
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Living organisms are highly complicated at the molecular level
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In
humans and animals, energy needed for work and biosynthesis of cellular structures is derived

from organic molecules in the diet
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In animals, energy is derived from the
breakdown of fuel molecules by processes referred to as catabolism
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The flow of energy in biological systems is covered in the discipline known as
bioenergetics
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Most of our use of thermodynamics will be concerned with the
calculation of free energy changes (∆G) which can be used to determine the direction of
metabolic reactions and their equilibrium constants
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Negative values of ∆G signify favorable reactions,
whereas positive values of ∆G are associated with unfavorable reactions
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This is important
because it will show how a cell can ratio reactions in different directions
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So reactions
can be thermodynamically favorable but kinetically unfavorable
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Bioenergetics is one of the tools used in animal
and human nutrition
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In this course, we will discuss energy metabolism in different
physiological states such as exercise and fasting, and in diseases such as diabetes
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Biochemistry and evolution
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In fact, only through biochemistry have we come to appreciate that all living
organisms are similar at the molecular level
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For this reason, much of what we
can learn about simple organisms such as Escherichia coli can be applied to the study of higher
organisms such as us
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Carl Woese determined by comparisons of ribosomal RNA (rRNA) sequences
that it is possible to construct a highly accurate tree of life showing the evolutionary relationship
between all life forms
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At the end of the course we will
discuss the properties of one of the most important enzymes used in modern biochemistry
laboratories, Taq polymerase
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Pk
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Chap
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"Water"
Reading Assignment: pp
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Problem Assignment: 1-5, 7, 8, 11, 13, 15 and 16
I
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While modern biochemistry tends to focus on the structure and function of molecules
such as proteins and DNA, it is important to keep in mind that biomolecular structure and
function are dictated by the properties of the medium in which they are dissolved
...
As an illustration of the importance of water in biological systems,
consider the formation of biological membranes
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As a consequence,
glycerophospholipids and other membrane lipids cluster together leading to structures such as the
cytoplasmic membrane and membranes of organelles
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These topics are essential for
understanding everything that will be discussed in later chapters of the text
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General properties of water molecules
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This arrangement results in a net dipole in which the end of the molecule
containing the unshared electrons has partial negative character and the end containing the 2
hydrogens has partial positive character (Fig
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1)
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Due to the fact that
a net dipole exists in individual water molecules, water is regarded as a polar solvent
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2
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III
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Neighboring molecules in bulk water are held together by non-covalent bonds known as
H-bonds
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2
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In the figure, the Hbond is the non-covalent attraction (dashed line) between the partially positively charged H atom
attached to the left oxygen atom and one of the unshared electron pairs (not shown) of the
oxygen atom on the right
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Thus, each water molecule can H-bond to 4 neighbors
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2
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In ice, water molecules
are organized in a rigid, precisely tetrahedral crystalline lattice (Fig
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5) where each molecule is
H-bonded to 4 others
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4 others on
average
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e
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While
a roughly tetrahedral arrangement of molecules is present, liquid water is more dense than ice

because the somewhat irregular packing of molecules allows them to fit together a bit closer
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The cohesiveness of molecules confers a
high melting point and boiling point in spite of the low molecular weight of water (18 g/mol)
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It also explains why cold water can quickly conduct heat
away from a swimmer leading to hypothermia and possibly death
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Behavior of ionic and polar substances in water
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Substances that can dissolve readily in water are referred to as
hydrophilic
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g
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2
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Because the interactions are energetically favorable, the salt
dissolves
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" The shells of
surrounding water molecules shield the ions preventing them from strongly interacting and
reforming the crystal
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The different types of H-bonds that can form are
discussed below
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Thus, the actual solubility of biomolecules is quite variable and depends on the
relative proportions of polar and nonpolar regions (Table 2
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V
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Nonpolar substances are relatively insoluble in water and therefore are referred to as
hydrophobic
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They generally lack polar groups that can interact with water
molecules
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Indeed cage-like structures known as clathrates are formed which can be
viewed as rigid geodesic domes surrounding the nonpolar molecule
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To
avoid this situation as much as possible, the suspended hydrophobic substances coalesce which
reduces the surface area of the nonpolar molecules in contact with water
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It is
important to note that hydrophobic interactions are not a type of chemical bond per se
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These
molecules have significant proportions of both hydrophilic and hydrophobic functional groups
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2
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This
schizophrenic combination results in the hydrocarbon chains clustering together away from
water contact when SDS is added to water
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2
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At an air-water surface SDS molecules actually line up
with their hydrocarbon tails pointing up into the air and the sulfate groups in contact with water
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Its hydrocarbon tail will bind to nonpolar surfaces, such as greasy dirt,

and dissolve it within the interior of the micelle
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VI
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Weak, reversible bonds (noncovalent bonds or noncovalent interactions) mediate
interactions between biomolecules
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However,
because they are individually weak, biomolecules exhibit flexibility which is important in
processes such as enzyme catalysis
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Generally, noncovalent interactions
are less than 1/10 th as strong as covalent bonds such as the -C-H bond
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e
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2
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A
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Charge-charge interactions occur between oppositely charged functional groups or ions
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The strength of these
bonds is inversely dependent on the square of the distance separating the charges
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Repulsive forces between like charges also can
play an important role in biological processes
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H-bonds
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In general, an H-bond is defined as a dipolar attraction between the
hydrogen atom attached to one electronegative atom, and a second electronegative atom
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Common types of H-bonds are shown in Fig
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10
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The distance between the two electronegative atoms in an H-bond is ~0
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H-bond strength is highly dependent on the alignment of molecular orbitals in the
interacting molecules and is strongest when they are lined up properly
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g
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2
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C
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These forces are attractions between oppositely oriented dipoles that are transiently
induced in the electron clouds of closely interacting molecules
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In fact, these forces become
destabilizing and push molecules apart if molecules are compressed more tightly together (Fig
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12)
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van der Waals forces typically are the weakest of the noncovalent

interactions (Fig
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13)
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They also can mediate specific interactions because they become
collectively strong if the interacting molecules have precisely complementary shapes and can
approach one another closely
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Water is a nucleophile
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The unshared pairs of electrons in
water molecules can behave as nucleophiles which can attack an electrophilic center in another
molecule
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2
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Although this is a favorable reaction, peptide bonds are actually quite stable
due to the fact that the activation energy for this reaction is quite high
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VIII
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As a prelude to our discussion of pH, we need to discuss the ionization of water, as it is
through this reaction that solution pH ultimately is established
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The products of this reaction are a hydronium ion (H3O+) and a hydroxyl ion (OH-)
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A hydroxyl ion can accept a proton from an acid and thus is called a base (proton
acceptor)
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[H+][OH-]
Keq =

[H2O]

Keq for water has been experimentally determined by measuring the electrical conductivity of
pure water
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The
value for Keq = 1
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This Keq value and the value of the concentration of water ([H2O]
= 55
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8 x 10

[H+][OH-]
M =
(55 M)

KW = (55
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8 x 10-16 M) = [H+][OH-]
KW = 1 x 10-14 M2 = [H+][OH-]
The constant, KW, is called the ion product of water
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This result leads directly to a definition of a "neutral solution" and to a definition of the
pH scale
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When these concentrations
are equivalent, [H+] = [OH-] = 1 x 10-7 M
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Likewise the addition of an acid which consumes hydroxyl ions leads to an excess
of hydronium ions and an acidic solution
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The pH scale
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pH is defined as
pH = -log [H+] = log (1/[H+])
By using logarithms, concentrations in the range of 1 M to 10-14 M H+ are converted to numbers
between 0 and 14
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0
A table relating the pH scale to the concentrations of H+ and OH- in solution is presented
in Table 2
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Solutions in which pH = 7
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Solutions with pH < 7
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0 are called "basic
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2
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X
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A
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Most reactions are reversible, and equilibrium is achieved when the rate of the forward
reaction becomes equal to the rate of the reverse
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A + B

C + D
[C][D]

Keq =

[A][B]

Remember, all reactions have a characteristic Keq at a defined temperature
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Unlike strong acids (HCl,
H2SO4, etc
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Equilibrium reactions for the dissociation of strong acids, strong bases, and the weak
acid, acetic acid (CH3COOH) are shown below
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acid)

CH3COO- + H+
(conj
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B
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The equilibrium constant for dissociation of a weak acid (HA) is
HA
(conj
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base)

[H+][A-]
Keq =

[HA]

The equilibrium constant for acid dissociation is more commonly called the acid dissociation
constant, Ka, and Ka = Keq
...
"
As in the case of pH, biochemists typically use "pKa" values instead of Ka values for
weak acids
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" pKa values for a number of
weak acids are listed in Table 2
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C
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The Henderson-Hasselbalch equation describes the quantitative relationship between pH
and pKa in buffer solutions
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The HH equation
will be derived in class starting from the equation specifying the equilibrium constant for
ionization of a weak acid, Ka = [H+][A-]/[HA]
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The equation can be used to calculate the pH of a
solution of a weak acid when the ratio of [A-]/[HA] is known, or alternatively, to calculate the
ratio of [A-]/[HA] when the pH is known
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Measurement of pKa by titration
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In a titration experiment, a weak
acid in solution is converted to its conjugate base by the addition of a strong base
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g
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Thus, the numbers of moles of weak acid in solution is the same as the
number of moles of strong base needed to convert all conjugate acid molecules to their conjugate
base form
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CH3COOH + Na+ + OH- →

CH3COO- + Na+ + H2O

During the titration, two equilibrium reactions are occurring simultaneously
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When the H+ ion is removed, a molecule of the conjugate acid form of acetic acid dissociates a
proton to restore equilibrium
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Likewise, a strong acid (e
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, HCl) will stoichiometrically convert a weak base to its
conjugate acid
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An example of a titration curve is shown using acetic acid in Fig
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17
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The change in pH is least at the midpoint of the curve, i
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, when 0
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This middle region of the curve is the optimum buffering region
for the weak acid, i
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, the pH changes least on addition of a strong base or strong acid
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Problem 1
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Thus,
pH = pKa + log (1/1)
pH = pKa + 0
pH = pKa
Problem 2
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2) at pH = 8
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4 = 7
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2 = log ([A-]/[HA])
101
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8/1 = [A-]/[HA]

Problem 3
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g
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2
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The only difference is that instead of having one plateau, the titration curve of a
"polyprotic" compound shows a plateau for each of its dissociable protons
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XI
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A buffer is "a solution that tends to resist a change in pH on addition of a small amount of
strong acid or base
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The optimum buffering
power of the solution occurs at the midpoint (where pH = pKa, and [CH3COOH] = [CH3COO-])
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In
this pH range, buffering power is best because the concentrations of both buffering species, HA
and A-, are the highest
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For example, acetic acid (pKa = 4
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76 < pH < 5
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0) is a good buffer for the range 7
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0
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In this case it is the second
dissociation reaction with pK2 = 7
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2
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H2PO4-

H+ + HPO42-

In the blood, the CO2-carbonic acid-bicarbonate system (Figs
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20 & 2
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Here the major forms responsible for buffering are carbonic acid and bicarbonate
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4, H2CO3 readily converts to CO2 and H2O which tends to shift the carbonic acidbicarbonate equilibrium to the left (to a higher pKa) which is closer to the pH of blood
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4
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Definition of a logarithm:
The logarithm of number is the value of the exponent that is needed to express the number as a power of
10
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That is
log10 y = x
expresses the same relationship as
y = 10x
When you take the logarithm of a number, you are calculating the exponent x
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e
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Relationships between scientific notation and logarithms
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0000001
0
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00001
0
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001
0
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1
1
10
100
1,000
10,000
100,000
1,000,000
10,000,000

1 x 10-7
1 x 10-6
1 x 10-5
1 x 10-4
1 x 10-3
1 x 10-2
1 x 10-1
1 x 100
1 x 101
1 x 102
1 x 103
1 x 104
1 x 105
1 x 106
1 x 107

-7
-6
-5
-4
-3
-2
-1
0
1
2
3
4
5
6
7

Application to pH
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