Module 1 - Topic 1 - The Chemistry of Life

7/30/2019 Module 1 - Topic 1 - The Chemistry of Life

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Biochemistry: The Chemistry of Life

Proteins, Enzymes, Lipids, Carbohydrates


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Teaching team member: Dr Ian Cock

Assoc. Prof. Dianne Watters (Convenor) Room: N34, 2.35 (Nathan campus)Ext: 57383 Email: [email protected]


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Lehninger: Principles of Biochemistry by David L Nelson and Michael M Cox.

5th edition, Worth Publishers 2008.

Packaged with:

The Study Skills Handbook 3rd

ed.By Stella Cottrell. Palgrave Macmillan2008


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Alternative text books

Matthews et al . Biochemistry 3rd edition, Addison, Wesley & Longman Inc. 2000.

Useful website for Matthews with quizzes:http://www.aw-bc.com/mathews/

Fundamentals of Biochemistry By DonaldVoet, Judith Voet and Charlotte Pratt, 3rdedition, Wiley Publishers 2007.


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Available Online through PubMed

Biochemistry

Jeremy M. Berg, John L.Tymoczko, Lubert Stryer

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed


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Workshop (participation & assessment) 20%

Module Quizzes 15%

Module Quiz 1 (modules 1-2, week 5)Module Quiz 2 (modules 3-4, week 9)Module Quiz 3 (modules 3-4, week 13)

Take home assessments 15%Take home 1 (modules 1-3, week 7)Take home 2 (modules 4-6, week 12)

End of Semester Exam 50%

All assessment items must be attempted to gain credit for

the course


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Attendance and participation in the workshops is compulsory.

If you are unable to attend a workshop then contact the Course

Convenor (A/Prof. Dianne Watters) to arrange to attend analternative workshop or provide a medical certificate if you areunable to attend another class.

Any course material covered in the lectures, workshops, andthe relevant sections of the textbook are examinable.

Important: Read the Course Profile on L@GCheck your email regularly


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At the start of each Module a set of workshop questions will beput on the Learning@griffith website.

You are expected to have attempted the workshop questionsprior to attending the workshop.

There will be a short quiz at the end of the workshop. There aresix workshops in total and the quizzes are worth 20% overall.

Remember: All workshops are compulsory, if you are unable toattend a workshop then you will need to provide a medicalcertificate.


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During this course you will be required to use keypads inlectures and workshops to respond to concept questions.

All responses are

Available in the libraryfor semester loan.

In order to obtain workshop participation marks you musthave a keepad


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HOW TO USE THE KEYPADS

Please note: All responses are

ANONYMOUS

Simply press the button thatcorresponds to the answer you

wish to select.

You will need these for Fridays lecture


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1. Choose your response from thekeypad buttons.

2. The light will go GREEN to confirmyour response has been received.

3. You can change your answer bysimply keying in your new choice.

(The system will only count the last vote)

HOW TO USE THE KEYPADS

NOTE:

Please DO NOT press the GO button,this is a functionality for break-out sessions only.


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CHANGING CHANNELS

Press (then release) the GO button onyour keypad.

While the light is flashing Red andGreen promptly enter the channelnumber.

The light should stay a steady Amber colour.

Immediately press GO again.

Now the light should be a steadyGreen colour .

EXAMPLE: For channel to 41.PRESS: GO 41 GO


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Have you used clickers in aclassroom before?

Y e s

N o

50%50%

1. Yes

2. No


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Why are you taking this course?

r e

q u i r e

d f o r t h

e p . . .

r e

q u i r e

d f o r t h

e p . . .

h o u g

h t i t m i g

h t b e

a . . .

n e e d

e d a s c i e

n c e o

. . .

25% 25%25%25%

1. Its required for theprogram Im in.2. Its required for the

program I want toget into.3. I thought it might be

an interesting option.4. I needed a science

option.


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Which of the following fields isbiochemistry NOT relevant to?

I m m u

n o l o g

y

N u t r i t

i o n

W a s t e

m a n a

g e m e n t

B r e w

i n g

N e u r o

s c i e n c

e s

N o n e

o f t h e

a b o v

e

17% 17% 17%17%17%17%1. Immunology2. Nutrition3. Waste

management4. Brewing

5. Neurosciences6. None of the above


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Which of the following best describeshow you feel about this course?

20%

20%

20%

20%

20%

1. Confident

2. Interested3. Worried

4. Nervous5. Bored


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This is not learning !

Learning is an active process!

The onus is on you, we can help, but we cant do if for you

www.huntington.edu

We are not going to spoon feed you information!


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ACTIVE LEARNING involves students doing things and thinkingabout what they are learning. Students participate in the learningprocess and apply the knowledge, not just acquire it. It is about

being a participant: actively engaging with the material and not just being a passive recipient


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Knowledge needs to be more than just a collection of facts ; acquiring knowledge should be a reflective and

ongoing process of examining information, evaluatingthat information and adding it to your understanding.


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Passive

Active


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Memorization of facts

Exam


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Critical thinking is based on reflective thinking that is focusedon interpreting, analysing, critiquing, synthesising, andevaluating information, arguments and experiences with a set

of reflective attitudes, skills and abilities to guide thoughts,beliefs and actions (Ruggiero, 1989).

Critical thinking skills enable people to evaluate, compare,analyse, critique and synthesise information.

Critical thinkers know to keep an open mind and may

re-think their views based on new knowledge.


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Critical thinking and success strategies:

1. Consciously raising questions. Why, how, what if?2. Being aware of gaps in information

3. Distinguishing between observation and inference; fact andconjecture,

4. Probing for assumptions5. Appropriately drawing inferences from data6. Performing hypothetical deductive reasoning7. Discriminating between inductive and deductive reasoning8. Testing ones own line of reasoning

9. Being aware of ones own line of reasoning


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What employers want

Good communication skills, written and oral

Problem solving and critical thinking skills Good work ethic Initiative, motivation, creativity Information literacy Ability to work autonomously and in teams

Time-management skills Flexibility, leadership, ambition

Lifelong learning skills _ self reflection


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0

10

20

30

40

50

60

70

80

90

HD D C P PC F

final grade

% a

t t e n

d i n g

2 / 3 l e c t u r e s


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Harvard one-minute evaluation

What were the most important things Ilearned from this lecture?

What questions do I still need explained?

After the lecture


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Come to lectures. Reflect on the important points of thelecture immediately after.

Read widely, especially the textbook and recommended

readings. Focus on understanding the important concepts

Dont try and memorise material you do not understand.

Come to workshops prepared .

Form study groups.

Seek help early if you need it . Work throughout the semester, you will not be able to cram

before the exam.


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Module 1 (Lehninger pages 43-64, 71-85)- Water & pH- Protein diversity

- Amino acids & peptide bonds

Module 2 (Lehninger pages 113-131, 135-140)- Primary, secondary & tertiary structure

- Fibrous proteins

Module 3 (Lehninger pages 140-143, 152-170)- Aspects of protein folding

- Globular proteins


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Module 1 (Lehninger pages 43-64, 71-85)- Water & pH- Protein diversity

- Amino acids & peptide bonds


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1. Water plays a central role in the chemistry of all life.

2. Proteins, polysaccharides, nucleic acids and membranes all

assume their characteristic shapes in response to water.

3. The chemical properties of water are related to the functionsof biomolecules, entire cells, and organisms.


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1. Hydrogen bonding

2. Ionic interactions

3. Hydrophobic interactions

4. van der Waals interactions

Weak interactions are crucial to macromolecular structure andfunction


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Important properties of water arise from itsangled shape.

Angle of 104.5 between two covalentbonds.

bonding orbital - sp 3.

Polar O-H bonds due to unevendistribution of charge .

The oxygen nucleus attracts electronsmore strongly than does the hydrogennucleus the electrons are more often inthe vicinity of the oxygen atom (2 -) than

the hydrogen ( +

). Angled arrangement of polar bondscreates a permanent dipole for a water molecule.


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Water molecules attract eachother due to their polarity.

A hydrogen bond is formedwhen a partially positivehydrogen atom attracts thepartially negative oxygen atomof a second water molecule.

Hydrogen bonds can formbetween electronegative atomsand a hydrogen attached toanother electronegative atom.


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A water molecule can form up to four hydrogen bonds.

In liquid water at room temperatureand atmospheric pressure water molecules are:

- disorganized- in continuous motion

Each molecules forms hydrogen

bonds with an average of only3.4 other molecules.


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Why does ice float?

https://reader009.{domain}/reader009/html5/0425/5ae06db776977/5ae06dc9141ed.jpg


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In ice, each water moleculeforms the maximum of four hydrogen bonds, creating a

regular crystal lattice.

This crystal lattice of ice makesit less dense than liquid water,

and thus ice floats on liquidwater.

Hydrogen bonding between water molecules


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Hydrogen bonding between water molecules

www.whatischemistry.unina.it/en/acqua.html

Cohesive properties of water make it possiblefor insects to walk on it


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H-bond acceptor: Electronegative atom such as O or N with anion pair of electrons.

H-bond donor: Hydrogen atom covalently bonded to another electronegative atom.


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Hydrogen bonds are strongest when the bonded moleculesoriented to maximize electrostatic interaction, which occurswhen the hydrogen atom and the two atoms that share it are in

a straight line - that is, when the acceptor atom is in line withthe covalent bond between the donor atom and H - holdingtwo hydrogen bonded molecules or groups in a specificgeometric arrangement.


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Water as solvent. Water dissolves many crystalline salts by hydrating their component ions. The NaCl crystal lattice is disrupted as water moleculescluster about the Cl - and Na + ions. The ionic charges are partiallyneutralized, and the electrostatic attractions necessary for lattice formation

are weakened. G = H - T S, where H has a small positive value and T S a largepositive value; thus G is negative.


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G = H - T S

H = change in Enthalpy

Heat produced or absorbed

T = Absolute Temperature

S = change in Entropy Change in order or randomness

G = Change in free energy Energy available to do work Predicts if reaction is favourable.

Positive S Increase in entropy


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The molecules of the biologically important gases CO 2 , O 2 , and N 2 arenonpolar. Nonpolar gases are poorly soluble in water. The movement of molecules - from the disordered gas phase into aqueous solution constrainstheir motion and the motion of water molecules and therefore represents adecrease in entropy.


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www.columbia.edu


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Nonpolar Amphipathiccompounds forceenergetically unfavorable

changes in the structure of water.

Eg: Long-chain fatty acids

have very hydrophobic alkylchains, each of which issurrounded by a layer of highly ordered water molecules.


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Release of ordered water favorsformation of an enzyme-substratecomplex. While separate, both

enzyme and substrate forceneighboring water molecules into anordered shell. Binding of substrate toenzyme releases some of the

ordered water, and the resultingincrease in entropy provides athermodynamic push towardformation of the enzyme-substratecomplex.


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van der Waals interactions arise when two uncharged atomsare brought very close together, their surrounding electronclouds influence each other. Random variations in the

positions of the electrons around one nucleus may create atransient electric dipole, which induce a transient, oppositeelectric dipole in the nearby atom. The two dipoles weaklyattract each other, bringing the two nuclei together.


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All weak interactions can be said to be fundamentallyelectrostatic interactions. EXPLAIN


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Ionic bonds, hydrogen bonds and van der Waalsinteraction depend on the unequal distribution of

electrons, resulting in an unequal distribution of charge.


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Explain how the following statement appliesto biochemistry. Order can be generated byan increase in randomness.


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The statement refers to the hydrophobic effect.Specific complicated biochemical structures canform, as a result of the increase in entropy from

hydrophobic groups being removed from aqueoussolution.


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Pure water is slightly ionized.

The ionization of water is expressed by an equilibriumconstant.

The pH scale designates the H + and OH - concentrations.

Weak acids and bases have characteristic dissociationconstants.

Titration curves reveal the p K a of weak acids.


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Water is a neutral molecule with a very slight tendency toionize.

H2O H+ + OH -

Free protons (H +) dont actually exist, rather they exist ashydronium ions, H 3O+. 2H 2O H3O+ + OH -

For simplicity, however, we often represent these ions as H +.


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The proton of a hydroniumion can jump rapidly fromone water molecule toanother.

Therefore, the mobility of H+ and OH - ions in solutionare much higher than for other ions.

Proton jumping is thereason for acid-basereactions being among thefastest.


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H2O H+ + OH -

The ionization (dissociation) of water is described by theexpression

K = [H+

] [OH-

] (products)[H2O] (reactant)

where K is the dissociation constant

Because of the undissociated [H 2O] is much larger than theconcentrations of the component ions, it can be consideredconstant (unchanging), and incorporated into K to yield anexpression for the ionization of water Kw.

Kw = [H +] [OH -]

The value of Kw, the ionization constant of water is 10 -14 at25C.


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If the ionization constant of water is 10 -14 then theconcentration of H + in solution is 10 -7 mol/L with an equivalentconcentration of OH - ions.

Kw

= [H +] [OH -] [OH -] = Kw = 10 -14 = 10 -7 mol/L[H+] 10 -7

Since these values are very low and involve negative powersof 10, the pH scale can be used.

pH = -log 10 [H+] = log 1[H+]

Eg: Human blood plasma has a [H +] of ~ 0.4 x 10 -7 mol/Lor 10 -7.4 mol/L which gives a pH of 7.4


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The value where an equal amount of H + and OH - ions arepresent is termed neutrality: at 25C the pH of pure water is7.0. At this temperature pH values below 7.0 are acidic andabove pH 7.0 are alkaline.

Neutral solutions change with temperature, due to enhanceddissociation of water with increasing temperature.

Always remember that the pH scale is logarithmic, and not alinear one. Thus a solution of pH 3.0 is not twice as acidic as asolution at pH 6.0 but 1000 times more acidic (ie: contains1000 times more H + ions).

http://www.authorstream.com/Presentation/ariedl-307910-ph-scale-hydrogen-ions-science-technology-ppt-powerpoint/


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Acid a compound that acts as a proton donor in an aqueoussolution.

Base a compound that acts as a proton acceptor in anaqueous solution.

Conjugate pair an acid together with its corresponding base.

By the above definitions, an acid-base reaction can be writtenas

HA + H 2O H3O + + A -


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HA + H 2O

H3O+

+ A-

An acid (HA) reacts with a base (H 2O) to form a conjugatebase of the acid (A -) and the conjugate acid (H 3O+).

Eg: acetate ion (CH 3COO -) is the conjugate base of aceticacid (CH 3COOH) and the ammonium ion (NH 4+) is theconjugate acid of NH 3.

The acid-base reaction is usually abbreviated toHA H+ + A -

The participation of water in the reaction is implied.

An alternative expression for a basic solution is

HB + H+ + B


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The strength of an acid is specified by its dissociation constant,or its efficiency as a proton donor.

The equilibrium constant for an acid-base reaction is expressedas a dissociation constant.

K = [products] = [H 3O+] [A -][reactants] [HA] [H 2O]

In dilute solutions, the water concentration is essentially constant55.5 M. Therefore, the term [H 2O] is customarily combined withthe dissociation constant, to take the form.

For an acid HA = H + + A -

At equilibrium Ka = K [H 2O] = [H +][A -][HA]

Thus, the stronger the acid the greater the value of Ka.


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Because the acid dissociation constants, like [H +] values arecumbersome to work with, they are transformed into pK valuesby the formula.

pK = -logKa analogous to pH = -log [H +] = log 1[H+]

Acids can be classified according to their relative strengths, thatis, their ability to transfer a proton to water.

Weak acids K < 1 strong acids K >> 1

Virtually all the acid-base reactions in biological systems involveH3O +, (OH -) and weak acids (and their conjugate bases).


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The pH of a solution is determined by the relative concentrationof acids and bases. The relationship between the pH of asolution and the concentrations of an acid and its conjugatebase can easily be derived.

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

Take negative logs: -log [H +] = -log Ka -log[HA]

[A-

]

or -log [H +] = -log Ka + log [A -][HA]

Thus, pH = pKa + log [A -][HA]


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The Henderson-Hasselbach Equation

Relates the extent of ionisation of a weak acid (and base) to thepH of the solution.

This equation is of fundamental importance in preparing buffer solutions to control pH during biochemical reactions.


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The ionisation characteristics of some of thesecompounds/groups actually controls the pH in cells andphysiological fluids so pH varies only over a narrow range.

In Blood the pH is regulated to stay in the range 7.35 7.45


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Three important points: pH = pKa + log [A-][HA]

1. pH depends on pKa and [A -][HA]

2. [A -] depends on pH and pKa[HA]

log [A -] = pH - pKa[HA]

3. At half-equivalence pH = pKa


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The concentration of the acidin the original solution can becalculated from the volumeand concentration of NaOHadded and a titration curveplotted.

At the midpoint of the titration,at which exactly 0.5equivalent of NaOH has beenadded, [HA]=[A -] and pH=pKa.


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The titration curves of these acidshave the same shape, they aredisplaced along the pH axisbecause the three acids havedifferent strengths. Acetic acid, withthe highest K a (lowest p K a) of thethree, is the strongest (loses itsproton most readily); it is alreadyhalf dissociated at pH 4.76.Dihydrogen phosphate loses aproton less readily, being half dissociated at pH 6.86. Ammoniumion is the weakest acid of the three

and does not become half dissociated until pH 9.25.


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Buffers are mixtures of weak acids and their conjugate bases.

A simple expression relates pH, p K a, and buffer concentration(Henderson-Hasselbalch equation ).

Weak acids or bases buffer cells and tissues against pHchanges.


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Buffer are mixtures of weakacids and their conjugatebases.

Buffers are aqueous systemsthat tend to resist changes inpH when small amounts of acids or base added.

A mixture of equalconcentration of acetic acidand acetate ion, found at the

midpoint of the titration curveis a buffer system.

The secretions of the stomach have a


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[H+] of 0.01M. What is the pH?

1 2 1 0 1 2

25% 25%25%25%

1. 12. 23. 104. 12

In the equilibrium reaction below, what is theeffect of adding H + in the form of HCl?


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T h e s

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n w i l l b

e . . .

T h

e e q u

i l i b r i u

m w i l

l s h . . .

T h

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i l i b r i u

m w i l

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T h e c

h l o r i d

e i o n s

w i l l . . .

25% 25%25%25%

CH 3COOH + H 2O CH 3COO - + H 3O+

1. The solution will become morebasic2. The equilibrium will shift to the

right3. The equilibrium will shift to the

left4. The chloride ions will react with

acetic acid to form chloroaceticacid


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Definition: A macromolecule composed of one or morepolypeptide chains, each with a characteristic sequence of amino acids linked by peptide bonds.

Proteins are the most abundant biological molecules,occurring in all cells and all parts of cells.

Range in size from relatively small peptides to huge polymersof molecular weights in the millions.

Proteins occur in great variety and exhibit enormous diversity

in biological function.


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Enzymes Transport proteins Nutrient & storage proteins Contractile & motile proteins Structural proteins

Defence proteins Regulatory proteins Specialized proteins


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http://publications.nigms.nih.gov/structlife/chapter1.html


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Definition: A biomolecule, either protein or RNA, that catalyzesa specific chemical reaction.

Eg: - Triose phosphate isomerase

- Serine proteases trypsin & chymotrypsin


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Myoglobin & Hemoglobin transport O 2 from the lungs toperipheral tissues.

Lipoproteins in blood plasma carry lipids to the liver and other

tissues.Cell membrane proteins transport molecules and ions across

membranes.


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Plant seeds store nutrient proteins needed for embryonicgrowth.

Ovalbumin (egg white) and Caesin (milk) are examples of

animal nutrient proteins.

Other proteins store non-nutrient molecules and ions (eg:ferritin).


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Actin and Myosin are the keyproteins involved in themovement of skeletal muscle.

Tubulin microtubules arecomponentsof flagella and ciliawhich can move and propel cells.

ll ( f )


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Collagen (see figure) is acomponent of cartilageand tendons.

Elastin is found inligaments and is a fibrousprotein that stretches intwo dimensions.

Keratin makes up part of the fingernails and hair.

Silk fibres and spider webscontain fibroin.

I l b li i li d


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Immunoglobulins are specialisedproteins made in lymphocytesthat recognise and neutraliseforeign antigens (bacteria,

viruses and proteins).

Fibinogen & thrombin are involvedin blood clotting to preventblood loss.

Snake venoms, bacterial toxins &

toxin plant proteins all functionto protection of the organism.

I li i h h l b li


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Insulin is a hormone that regulates sugar metabolism.

Repressors are proteins that regulate the transcription of specific genes.

Th t i hi h h i li d f ti th t


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There are any proteins which have specialised functions thatare not easy to classify.

Antifreeze protein from Antarctic fish which prevent their blood

from freezing.


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It is quite amazing that only 20 amino acidsare able give rise to such an array of diversity.

Amino acid: amino substituted carboxylic acids the building


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Amino acid: -amino-substituted carboxylic acids, the buildingblocks of proteins

All amino acids have a carboxyland amino group bonded to an -carbon.

The -carbon also has a

hydrogen and a side chain (R-group).

carbon = central C atom with 4ff


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Each amino acid differs in the side chain whichvary in charge, size, structure, water solubilityand chemical properties.

Peptide bond: An amide linkage between the -amino group of one amino acid and the -carboxylic group of another.

carbon = central C atom, with 4different substituents (chiral):1. -carboxyl group2. -amino group

3. hydrogen atom4. R group = side chain

All amino acids with the exception of glycine are chiral and thusi i L d D i


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All amino acids with the exception of glycine are chiral and thusexist in L and D isomers.

Only L-enantiomers are found in proteins.

Enantiomers (non-superimposable complete mirror images)

The formation of stable repeating substructures in proteinsll i h i i i id b f


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The formation of stable repeating substructures in proteinsgenerally require their constituent amino acids to be of onestereochemical series.

Cells are able to specifically synthesize the L isomer of aminoacids because the active site of enzymes is asymmetric,causing the reactions they catalyze to be stereospecific.

All Amino Acids in naturally occurring proteinsare L- isomers.

-COOH group: a weak acidcan DONATE its proton


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COOH group: a weak acidcan DONATE its protonpKa ~ 2-3

What's the conjugate base form of the carboxyl group?Which form is charged?Is it a positive or a negative charge?

-NH2 group: a weak baseunshared pair of electrons on the :Nneutral amino group can ACCEPT a proton.pKa ~9-10

What's the conjugate acid form of the amino group?Which form is charged?Is it a positive or a negative charge?


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Aliphatic amino acids tend to be hydrophobic.


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Aliphatic amino acids tend to be hydrophobic.Become more hydrophobic as the side chain increases in

length.

Hydrophobic amino acids are usually buried in proteins for protection against aqueous environments.

Tend to be clustered together within proteins, stabilizingstructure by means of hydrophobic interactions.

Methionine is one of only 2 amino acids that contain sulfur. Itcontains a nonpolar thioester group in its side chain.


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Proline is a cyclic amino acid.


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Shares many of the properties of aliphatic amino acids.

The rigid nature of proline makesthe folding of proline intoproteins difficult.

Generally introduces a kink intopolypeptide chain.


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R groups of these animo acids are more soluble in water andmore hydrophilic than the nonpolar amino acids.


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more hydrophilic than the nonpolar amino acids.

Side chains contain functional groups that are able to form

hydrogen bonds in water.

Polarity is due to the hydroxyl groups of serine and theonine,the sulfhydryl group of cysteine and the amide groups of asparagine and glutamine.

Asparagine and glutamine are the amide derivatives of

aspartate and glutamate, respectively.

The side chain can ionize atmoderately high pH.


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It can form a covalently linked dimericamino acid called a cystine in whichtwo cysteine residues are joined toform a disulfide bond.

Play a special role in structures bycovalently links between differentparts of a protein or differentpolypeptides.

Disulfide linkages are stronglyhydrophobic (nonpolar).


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The R groups carry positivecharges and are strongly


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polar at pH 7.0.

They are very hydrophilic andusually found on the exterior of proteins.

Lysine has a secondary aminogroup on its aliphatic sidechain.

Arginine has a positivelycharged guanidino group.

Histidine contains a imidazolegroup.


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Is the only common amino acid

having an ionizable with a pKanear neutrality.

In enzyme catalysed reactions ahis residue facilitates thereaction by serving as a protondonor/acceptor.

R groups carry a netnegative charge at pH 7.0.


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Like the positively charged

amino acids they are veryhydrophilic.

Both aspartate andglutamate have a secondcarboxylic acid group .


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The R groups in this class are relatively nonpolar andparticipate in hydrophobic interactions.


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The hydroxyl group of tyrosine is also important because of its

ability to form H-bonds, and it is an important functional groupin some enzymes.

Tyrosine and tryptophan are significantly more polar thanphenylalanine because of the tyrosine hydroxyl group and thetryptophan indole ring.

Tryptophan, tyrosine and to a lesser extent phenylalanineabsorb ultraviolet light.

Alanine Ala A Arginine Arg R

Leucine Leu LLysine Lys K


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g g Asparagine Asn N

Aspartic acid Asp DCysteine Cys CGlutamic acid Glu EGlutamine Gln QGlycine Gly G

Histidine His HIsoleucine Ile I

y yMethionine Met M

Phenylalanine Phe FProline Pro PSerine Ser SThreonine Thr TTryptophan Trp W

Tyrosine Tyr YValine Val V

1. The structures of all 20 amino acids.

2 Th i h i l & h i l i


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2. Their chemical & physical properties.

3. Their one letter & three letter codes.

Properties of the 20 amino acids that occur inpeptides and proteins are crucial to the structure andfunction of proteins

Stereochemistry Relative hydrophobicity or polarity

Hydrogen bonding properties Ionization properties Other chemical properties

Why do we need to learn the amino acidstructures?


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Focus on Similarities not Differences

structures?

The following 7 slides are adapted from the Amino acid tutorial (www.tamu.edu)

Amino acids are the language of protein biochemistry.Without knowing these, it is impossible to think or talksensibly about proteins and enzymes

How to learn amino acid structures All amino acids have a common core structure that is built around the

alpha carbon. Side chains are denoted by R.R groups are the only variable groups in the structure.


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The R group gives an amino acid its structural identity and, its uniquebiochemical properties.

RR

COOH

C+H3N H

Focus on the R group to learn the structures

R groups build and interrelate. Four that illustrate this point

are glycine, alanine, phenylalanine and tyrosine.


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CH 3 CH 2

With R = H, glycine is the simplest amino acid. Alanine with a methyl group

is the next simplest. In Phenylalanine, a phenyl group replaces a H onalanines methyl group. Tyrosine is formed by adding an OH group to thepara position on the phenyl ring of phenylalanine .

H CH 2

OH

Glycine Alanine Phenylalanine Tyrosine

The acidic amino acids have negative () charges in their R group. Thereare two, aspartic acid and glutamic acid. Note their similarity. Glutamicacid has one more CH 2 group. Note that both have a COO groupwhich gives the negative charge.


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CH 2

Asparticacid

COO

CH 2

CH 2

GlutamicAcid

COO

The COO can exchange a proton with the solvent i.e. behave as an

acid. The suffix ate is used to designate an ionized acid (called a salt).Hence, aspartic acid and glutamic acid are referred to as aspartate andglutamate. The amide derivatives of aspartate and glutamate areasparagine and glutamine.

CH 2

COO C=O

NH2

Asparagine

CH 2

CH 2

COO C=O

NH2

Glutamine

Aspartate

Glutamate

The positively (+) charged amino acids are represented by lysine, arginine

and histidine.Lysine

Arginine Histidine


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CH 2CH 2CH 2

CH 2NH 3+

CH 2CH 2

CH 2

NH+H2N=CNH 2

CH 2

HN NH +

Guanidinium

Imidazole

Each is characterized by a (+) N in the R group. For lysine this groupis called the epsilon amino group. In arginine it is the guanidinium groupand for histidine it is the imidazole group.

Epsilon amino

Serine has a CH2OH for the R group. One H on the side chain of

alanine has been replaced with a hydroxyl group. Threonine is serinewith a methyl group. In Cysteine, the O in serine has been replaced


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y g p y , pwith an S.

CH 2OH H-C-OH

CH 3

CH 2S H

Methionine appears to combine cysteine with threonine. The nametells you methionine has a sulfur (thio) and a methyl group in thestructure.

CH 2CH 2

SCH 3

Serine Threonine Cysteine Methionine

These 3 branched-chain hydrophobic amino acids have only C and H in

their R groups. Valine is easy to remember because the carbon chain isarranged as the letter V. Leucine and isoleucine both have a 4 carbonR gro p Le cine resembles aline b t ith a CH before the V


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R group. Leucine resembles valine but with a -CH 2 before the V.Isoleucines side chain resembles the letter L.To distinguish these amino acids, focus only on the branched chains inthe R structure. Valine and leucine have only methyl groups, whereasisoleucines branches are one methyl and one ethyl group

C

CC

C

C

C

C

C

CCC

Valine Leucine Isoleucine

Ethyl group

Tryptophan is unique in having an indole ring attached to the core via aCH 2 group. Proline also has a ring, but this ring is aliphatic and saturated.

Tryptophan and Proline


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CH 2

Tryptophan

2 g p g, g pNote proline does not have a core structure. This is because the alphaamino group is incorporated into the ring.

N

H

Proline

N COO

H

CH 2

H2C

H2C

CH

Indole


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http://www.biology.arizona.edu/biochemistry

There are a number of modified amino acids which are formedfrom the common amino acids.


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Examples: 4-hydroxyproline (cell walls, collagen)

5-hydroxylysine (collagen)6-N-methyllysine (myosin) -carboxyglutamate (prothrombin)selenocysteine

Example: collagen, a fibrousprotein of connective tissue.


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p

Example: collagen, a fibrous protein of connective tissue.


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Example: a constituent of myosin, acontractile protein of the muscle.


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Example: found in the blood clottingprotein prothrombin and in certain Ca 2+binding proteins.


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Is introduced during protein synthesis rather than created through a post-syntheticmodification.


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-COOH group: a weak acidcan DONATE its protonpKa ~ 2-3


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What's the conjugate base form of the carboxyl group?Which form is charged?Is it a positive or a negative charge?

-NH2 group: a weak base

unshared pair of electrons on the :Nneutral amino group can ACCEPT a proton.pKa ~9-10

What's the conjugate acid form of the amino group?Which form is charged?Is it a positive or a negative charge?

pKas of -amino and -carboxyl groups are different for different amino acids, and are also altered if they are theterminal groups on a chain of Amino Acids i e a peptide


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terminal groups on a chain of Amino Acids, i.e., a peptideor protein.

Besides the -carboxyl and -amino groups, 7 of the 20 Amino Acids have ionizable side chains.

Amino acids are ionised in aqueous solutions.

At pH 7.0, the amino group is largely protonated (NH3+) and


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the carboxyl group largely deprotonated (COO-) forming a

zwitterion.

-Amino Acids, Ionization

-carboxyl group -amino group


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Berg et al., Fig. 2-6

Two distinct stages corresponding to

the deprotonation of carboxy groupand the amide group.


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At low pH glycine is fully protonated.

At the midpoint of this part of thetitration (point of inflection) the pH =pKa (pK1).

As the titration continues another inflection point is reached. At thispoint removal of the first proton iscomplete.

The second half of the titrationcorresponds to the removal of theproton from the amide.

It gives a quantitative measure of the pKa

of each of the ionizing groups.

There are two regions of buffering power,extending for approximately 1 pH unit


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extending for approximately 1 pH uniteither side of the pKa.

The relationship between net electriccharge and the pH of the solution canalso be derived from the titration curve.So at pH 5.97, glycine is present in itsdipolar form, fully ionized but with no netelectrical charge. This point is called theIsoelectric point or Isoelectric pH.

So at a pH < pI glycine has a net + charge& at a pH > pI glycine has a net - charge

The side chains of each amino acid are also ionisible and eachgroup has a specific pKa.

At pH > pKa the proton tends to be off.


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p p p At pH < pKa the proton tends to be on.

The average pKa for an amino acid approximates theisoelectric point (pI), where there is no nett charge.

As pH increases above the pI the net charge becomesnegative.

As pH decreases below the pI the net charge becomespositive.

When the amino acids are incorporated into proteins only thecharges on the side chains remain.


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Why is the His side chain (imidazole group) calledbasic


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if the predominant form at pH 7 is unprotonated?

Why is the His side chain (imidazole group) calledbasicif h d i f i d?


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if the predominant form at pH 7 is unprotonated?

Which of the 20 amino acids is achiral (has no asymmetric C)?

Which aliphatic Amino Acid has 2 chiral centers?


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Which of the aromatic side chains would be the least polar (the most

hydrophobic )?

Do any of the aromatic side chains have an ionizable group (the ability todissociate a proton)? Which? Approx. pKa?

Which of the two S-containing side chains would be more hydrophobic?

Are the amide side chains of glutamine and asparagine ionizable, i.e. canthey gain or lose a proton? Why or why not?

Documents

Module 1 - Topic 1 - The Chemistry of Life