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Biochemistry 404

elcome to the most intriguing course you will take in colleg

Mark Hargrove
Dept. of Biochemistry, Biophysics, & Molecular Biology

Mainpointsfromthislecture.
Whystudybiochemistry?
Howwillthiscourserun?
Theimportanceofbiochemicalunity
Theimportanceofwaterandweakforces
AreminderofpHandbasicthermodynamics

Overview of Biochemistry

The discipline of biochemistry seeks to explain life

processes in terms of the fundamental chemical principles

- growth, reproduction, senses, response to the environment, etc.

Biochemistry is a reductionist approach in which specific


molecules are separated from the living organism and
studied in a test tube environment

- information thus collected on thousands of biomolecules must


then be integrated into a systematic understanding of life
processes

Biochemistry, molecular biology, cell biology, genetics are


merging into an integrated field of molecular bioscience

- dont be surprised if youve seen some of this material in other


-

courses
the context and level of detail will usually be different in this one

Organizational Themes (i)

Biomolecules are often polymers assembled from


repeating building block units

- proteins, carbohydrates, lipids, nucleic acids

The three dimensional structure of biomolecules

determines their chemical and biological functions

The unit of biological function is the cell, which

contains both water-based chemical environments


and organic molecule-based chemical environments

Energy input from the environment is continually

necessary to maintain the chemical reactions of life

- life systems capture energy from the environment and use


it to maintain order within the organism

Organizational Themes (ii)

Ordered sets of chemical reactions, i.e., metabolic


pathways, accomplish interconversions between
biomolecules

Chemical reactions in living systems are catalyzed


by specialized proteins called enzymes

Information is stored in chemical form by nucleic


acids and this information ultimately determines
biological function

Why Study Biochemistry?

To obtain a fundamental chemical understanding


of life

- to understand the differences between living and nonliving matter

To advance the areas of medicine, health,


nutrition, and the environment

- e.g., most pharmaceuticals are discovered by the

application of biochemistry information (in some form or


another)

To advance other technologies though the

application of biochemistry materials science,


renewable resources, biotechnology, etc.

Mainpointsfromthislecture.
Howwillthiscourserun?
(letslookatthesyllabus)

Historical
Development of
Biochemistry as a
Discipline
Physical and chemical

sciences characterize
biomolecules in chemical
terms

Genetics, cell biology,

molecular biology identify


biological functions and
correlate them with specific
biomolecules

Fusion of the two sciences,

chemistry and biology, allows


explanation of life processes
in terms of fundamental
chemical principles

Biochemistry is a
young field!

Theearthisold.

ClairPatterson
19221995
HewasfromMitchellvilleIowa,andmeasuredtheageoftheearth:
4.55billionyears.HisworkalsoleadtotheCleanAirAct(1970)

Theroadmapoflife
prebioticworld

Biochemicalunityunderliesbiologicaldiversity

TATA-box binding protein

Biochemicalunityunderliesbiologicaldiversity:
Thisisoneobservationthatsupportsspeciationandacommon
biochemicalunderstandingofbiology

Generalbiochemistryissharedbytheseorganisms:
ItdoesntHAVEtobethisway,yetitis.

Molecular Scale in
Biological Systems
Atoms - Angstrom units, 0.1
nm

Small molecules, building


blocks - about 1 nm

Polymers, such as proteins or


polysaccharides - about 5 nm
diameter

Virus particles - about 50 nm


Chloroplasts and mitochondria
- about 5000 nm (5 m)

Prokaryotic cells - 1 to 10 m
Eukaryotic cells - 10 - 100 m
Eukaryotic organisms - 106 m
(1 m), so very many cells in
the organism

ow many cells are in a human?

WATER WATER EVERYWHERE!

WATER WATER EVERYWHERE!


TISSUE
Heart
Skeletal muscle
Lung
Brain
Tomato
Whole milk
Bread
Flour

% WATER
83
79
79
77
94
87
36
12

Functions of Water in Biological


Systems
Solvent
Most small organic molecules in biological systems are soluble in

water
nutrients used for generation of energy
building block compounds used for assembly of polymeric
biomolecules
Compartmentalization through the hydrophobic effect
Hydrophobic organic molecules are not soluble in water
hydrophobic molecules, mostly lipids, separate from the waterbased solution
barriers are created between water-based compartments
Buffer for temperature and pH
high heat capacity means temperature stays relatively constant
chemical system for absorption and release of protons allows the
concentration of protons (pH) to remain relatively constant
and Participation in Chemical reactions...

Structure of Water
tetrahedral arrangement of sp3
orbitals around oxygen

two sp3 orbitals are full, two share


electrons with hydrogen atoms

electronegativity of oxygen draws


electrons from hydrogen nuclei

water molecules participate in

many H-bonds with each other,


forming extended H-bonded
networks

water molecules also H bond with


many dissolved biomolecules

the high frequency of H-bonds in

water gives it particular physical


properties suited for living systems

Hydrogenbondingisveryimportantinbiochemistry

~10kJ/mol

S-H------O

xamples of H-bonding

Extended H bond network of water


molecules

Individual water molecules can form up to four H bonds, one for each
H nucleus and 2 for the O nucleus
transient: each molecule breaks and reforms bonds every ~10-12 sec

Physical properties of water

High freezing and boiling points match earths temperature range


High heat capacity
energy required to increase temperature is high, so

temperature change is small


temperature is a measure of molecular motion, which is resisted
by
H-bonds in water
Solid is less dense than liquid because H-bonds in liquid are less
ordered, so ice floats (thats unusual and we wouldnt be here
without it)

Unique properties of water


Surface tension

Because of the hydrogen bonds between the water molecules,


the surface of the water behaves like an elastic membrane.

Polar and charged compounds are readily soluble in


water

Compounds that are soluble in water are hydrophilic


H bonds between water molecules and the solute explain this property

Waterisimportantalsobecauseweakforcesruleinbiochemistry
Electrostatic

1to5kJ/mol

vanderWaals

~2kJ/mol(peratom)

(Covalent is ~ 360 kJ/mol)


Types of Weak Bonds

Thehydrophobiceffect

Ch.12
(Waxes)

Examples of
water molecules
separating from
nonpolar atoms

Ch. 12

Why are we so fixated on weak bonds?

Weak Bonds Allow


Molecular
Recognition

Macromolecules can bind to each other


Molecular recognition is specific
the right spatial arrangements of weak

bonds is necessary
individual weak bonds cannot mediate
a stable association
many weak bonds summed together
are responsible for the association
Molecular recognition is often reversible

Thingsweneedtoknowaboutwaterchemistry
+

H + OH

H 2O

[H ][OH ]
K eq =
[H 2O]

[H2O]= 1000g18g/mole =55.5M

[H O] doesnt change so is disregarded


+

14

K w = [H ][OH ] = 1x10 M
2

[H ] = [OH ] = 1x10 M

AcidsandBases
+

Acid
H + Base

RCOOH H + RCOO

NH 4

H + NH 3

[H + ][A ]
Ka =
[HA]

pH Scale
Remember that the scale is logarithmic: a

difference in 1 pH unit = tenfold difference


in H+ concentration.

Sren Srensen 1909

Household bleach

DefinitionofpHandpKa
[H + ][A ]
Ka =
[HA]
+

pH = log(1/[H]) = log([H ])

(WaterpH=7)

pK a = log(1/K a ) = log(K a )
[H + ][A ]
log(K a ) = log(
)
[HA]

andsolveforpH

[A ]
pH = pK a + log(
)
[HA]

HendersonHasselbalchequation

The HendersonHasselbalch
Equation
This equation is an algebraic rearrangement of terms from the equation

that defines Ka
pH = pKa + log ([A-]/[HA])
Memorize this equation
Using the HH equation we can set the pH of a solution by knowing the pKa
and varying the amount of A- and HA
A- is provided by adding the salt, (such as Na +A-), which completely
dissociates
HA is added directly
the degree of dissociation is very small, so it can be neglected in the
equation

xample a solution of 0.1M acetate and 2M acetic acid (pKa 4.75)


gives a pH of 3.44.

Relevance of pKa
in biochemistry.
The functional groups with a low pKa (<7) are
deprotonated at neutral pH (like COOH is in the form
COO-), while groups with high pKa (>7) are protonated at
neutral pH (like NH3 is in the form NH4+).

[A ]
pH = pK a + log(
)
[HA]

Buffers

AtpH=pKa,[A]=[HA]

CH3COOH

1NHCl

1NHCl

Thermodynamicsandbiochemistry
1.Thetotalamountofenergyisconstant
2.Entropy(S)increasesforspontaneousreactions
3.S=0at0Kinaperfectlyorderedcrystal
Howcanlifeexistifentropymustalwaysincrease?

Entropyincreasesinthesurroundings

ThisistheimportanceofGibbsFreeEnergy;ittakesintoaccounttheentropyofthesystemanditssurroundings

G=HTS

Letstakeacloserlookattheseterms.

Enthalpy
The enthalpy change, H, is the heat released or absorbed for a

chemical reaction that occurs at constant volume and pressure


(no work done)
Enthalpy changes interconvert chemical bond energy with heat
released into the system
-H (i.e. energy release) favors a reaction, but does not by itself
determine if that reaction occurs spontaneously
consider dissolving H2SO4; the temperature of the solution
rises, because energy is released (-H)
consider dissolving KCl; the temperature of the solution drops,
because energy is absorbed (+H)
both of these reactions occur spontaneously

Entropy and Gibbs Free Energy


So, what does determine if a reaction occurs spontaneously?
Free energy change (G) takes into account both H and the

entropy change (S) for the reaction


entropy is a measure of randomness, or disorder, in the system
more randomness favors a reaction (second law of
thermodynamics)
G = H TS
-G indicates a reaction will occur spontaneously
this comes from -H and +S
However, the speed of a reaction is not defined by G!

Entropy and Gibbs Free Energy


-H overcomes -S; this is critical in building biomolecules, because
these big things are highly ordered and thus thermodynamically
unfavorable

Cells must expend chemical energy, or absorb light energy, to


maintain their high degree of order

Standard Gibbs Free Energy change: G


this is the free energy change when all the reactants and

products of a reaction are mixed together at 1 M concentration; it


must be measured!
pH is set at 7.0, pressure at 1 atm, temperature at 25 oC
the reaction is then let run to reach equilibrium
the change in total free energy of the system is G

Part 1: Introduction to Biomolecules (Ch.


1-5,7-13)
are polymers made up of amino acid
Proteins
building blocks

- amino acids contain one primary amine group and one


carboxylic acid group

Polysaccharides are polymers made up of

monosaccharide (simple sugar) building blocks

- monosaccharides usually have lots of hydroxyl groups


and one ketone or aldehyde group

Nucleic acids are polymers made up of

nucleotide building blocks (more detail later in


this lecture)

Lipids are not polymers but are made up of


fatty acid building blocks

- mostly alkane and alkene, with ester functional groups

Polymeric Biomolecules

First learn building block structures, then learn the


linkages between them

(chapters 15-18, plus extra stuff, and BBMB 40


Part 2: Metabolism

Along the way: Applications of Biochemical Knowledge Creativity at work

Nutrition
Medicine
Biomaterials
Nano-machines
Genetic Engineering
Feeding the entire world
Unlimited clean-burning fuel
Glowing mice and photographic bacteria