Module 1 - Topic 1 - The Chemistry of Life

Welcome to 1002BPS Structural Biochemistry
Biochemistry: The Chemistry of Life

Proteins, Enzymes, Lipids, Carbohydrates
1002BPS STRUCTURAL BIOCHEMISTRY MODULE 1
1002BPS Structural Biochemistry

Assoc. Prof. Dianne Watters (Convenor) Room: N34, 2.35 (Nathan campus) Ext: 57383 Email: d.watters@griffith.edu.au
Teaching team member: Dr Ian Cock

Room: N34, 1.20 (Nathan campus) Ext: 57637 Email: i.cock@griffith.edu.au
Text book
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 Macmillan 2008
AlternativeText books (in the library)

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 Donald Voet, Judith Voet and Charlotte Pratt, 3rd edition, Wiley Publishers 2007.
Available Online through PubMed

Biochemistry Jeremy M. Berg, John L. Tymoczko, Lubert Stryer
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
1002BPS Assessment
Workshop (participation & assessment) Module Quizzes 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 Take home 1 (modules 1-3, week 7) Take home 2 (modules 4-6, week 12) End of Semester Exam 50% 15% 20% 15%
All assessment items must be attempted to gain credit for the course
1002BPS Important information

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 an alternative workshop or provide a medical certificate if you are unable to attend another class. Any course material covered in the lectures, workshops, and the relevant sections of the textbook are examinable. Important: Read the Course Profile on L@G Check your email regularly
1002BPS Workshops
At the start of each Module a set of workshop questions will be put on the Learning@griffith website. You are expected to have attempted the workshop questions prior to attending the workshop. There will be a short quiz at the end of the workshop. There are six workshops in total and the quizzes are worth 20% overall. Remember: All workshops are compulsory, if you are unable to attend a workshop then you will need to provide a medical certificate.
Keepads
During this course you will be required to use keypads in lectures and workshops to respond to concept questions. All responses are ANONYMOUS
Available in the library for semester loan. In order to obtain workshop participation marks you must have a keepad
HOW TO USE THE KEYPADS

Simply press the button that corresponds to the answer you wish to select.
Please note: All responses are
ANONYMOUS
You will need these for Fridays lecture
HOW TO USE THE KEYPADS

1. Choose your response from the keypad buttons. 2. The light will go GREEN to confirm your response has been received. 3. You can change your answer by simply keying in your new choice. (The system will only count the last vote)
NOTE: Please DO NOT press the GO button, this is a functionality for break-out sessions only.
CHANGING CHANNELS
Press (then release) the GO button on your keypad. While the light is flashing Red and Green promptly enter the channel number. The light should stay a steady Amber colour. Immediately press GO again. Now the light should be a steady Green colour.
EXAMPLE: For channel to 41. PRESS: GO 41 GO
Have you used clickers in a classroom before?

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1. Yes 2. No
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Why are you taking this course?

1. Its required for the program Im in. 2. Its required for the program I want to get 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 is biochemistry NOT relevant to?

1. Immunology 2. Nutrition 3. Waste management 4. Brewing 5. Neurosciences 6. None of the above
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Which of the following best describes how you feel about this course?
1. 2. 3. 4. 5.
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Confident Interested Worried Nervous Bored
This is not learning!
www.huntington.edu
We are not going to spoon feed you information! Learning is an active process! The onus is on you, we can help, but we cant do if for you
ACTIVE LEARNING involves students doing things and thinking about what they are learning. Students participate in the learning process 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
Active learning
Knowledge needs to be more than just a collection of facts; acquiring knowledge should be a reflective and ongoing process of examining information, evaluating that information and adding it to your understanding.
The learning pyramid
Passive
Active
Levels of Learning
Exam
Memorization of facts
Levels of learning
Critical thinking
Critical thinking is based on reflective thinking that is focused on interpreting, analysing, critiquing, synthesising, and evaluating 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.
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 and conjecture, 4. Probing for assumptions 5. Appropriately drawing inferences from data 6. Performing hypothetical deductive reasoning 7. Discriminating between inductive and deductive reasoning 8. Testing ones own line of reasoning 9. Being aware of ones own line of reasoning
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
The importance of lectures

90 % attending 2/3 lectures 80 70 60 50 40 30 20 10 0 HD D C P PC F final grade
After the lecture Harvard one-minute evaluation

What were the most important things I learned from this lecture?
What questions do I still need explained?
Tips for success

Come to lectures. Reflect on the important points of the lecture 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.
Structural Biochemistry: Modules 1-3

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

- Primary, secondary & tertiary structure - Fibrous proteins

- Aspects of protein folding - Globular proteins
Structural Biochemistry: Modules 1

- Water & pH - Protein diversity - Amino acids & peptide bonds
Water
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 functions of biomolecules, entire cells, and organisms.
Weak interactions in aqueous solutions

1. Hydrogen bonding 2. Ionic interactions 3. Hydrophobic interactions 4. van der Waals interactions Weak interactions are crucial to macromolecular structure and function
Hydrogen bonding - unusual properties of H20
The structure of H20

Important properties of water arise from its angled shape. Angle of 104.5 between two covalent bonds. bonding orbital - sp3. Polar O-H bonds due to uneven distribution of charge . The oxygen nucleus attracts electrons more strongly than does the hydrogen nucleus the electrons are more often in the vicinity of the oxygen atom (2-) than the hydrogen (+). Angled arrangement of polar bonds creates a permanent dipole for a water molecule.
Hydrogen bonding
Water molecules attract each other due to their polarity. A hydrogen bond is formed when a partially positive hydrogen atom attracts the partially negative oxygen atom of a second water molecule. Hydrogen bonds can form between electronegative atoms and a hydrogen attached to another electronegative atom.
Hydrogen bonding between water molecules

A water molecule can form up to four hydrogen bonds. In liquid water at room temperature and atmospheric pressure water molecules are: - disorganized - in continuous motion Each molecules forms hydrogen bonds with an average of only 3.4 other molecules.
Why does ice float?
http://global-warming.accuweather.com/iceberg.jpg
Hydrogen bonding of ice

In ice, each water molecule forms the maximum of four hydrogen bonds, creating a regular crystal lattice. This crystal lattice of ice makes it less dense than liquid water, and thus ice floats on liquid water.

Cohesive properties of water make it possible for insects to walk on it
www.whatischemistry.unina.it/en/acqua.html
Examples of hydrogen bond acceptors & donors

H-bond acceptor: Electronegative atom such as O or N with an ion pair of electrons. H-bond donor: Hydrogen atom covalently bonded to another electronegative atom.
Some biologically important hydrogen bonds
Examples of hydrogen bond acceptors & donors

Hydrogen bonds are strongest when the bonded molecules oriented to maximize electrostatic interaction, which occurs when the hydrogen atom and the two atoms that share it are in a straight line - that is, when the acceptor atom is in line with the covalent bond between the donor atom and H - holding two hydrogen bonded molecules or groups in a specific geometric arrangement.
Polar, non-polar & amphipathic biomolecules
Ionic interactions
Water as solvent. Water dissolves many crystalline salts by hydrating their component ions. The NaCl crystal lattice is disrupted as water molecules cluster about the Cl- and Na+ ions. The ionic charges are partially neutralized, and the electrostatic attractions necessary for lattice formation are weakened. G = H - TS, where H has a small positive value and TS a large positive value; thus G is negative.
Ionic interactions
Positive S Increase in entropy
H = change in Enthalpy Heat produced or absorbed
G = H - TS
G = Change in free energy Energy available to do work Predicts if reaction is favourable.
T = Absolute Temperature
S = change in Entropy Change in order or randomness
Hydrophobic interactions
The molecules of the biologically important gases CO2, O2, and N2 are nonpolar. Nonpolar gases are poorly soluble in water. The movement of molecules - from the disordered gas phase into aqueous solution constrains their motion and the motion of water molecules and therefore represents a decrease in entropy.
Hydrophobic interactions
www.columbia.edu
Effects of nonpolar molecules in water

Nonpolar Amphipathic compounds force energetically unfavorable changes in the structure of water. Eg: Long-chain fatty acids have very hydrophobic alkyl chains, each of which is surrounded by a layer of highly ordered water molecules.

1 2

Release of ordered water favors formation of an enzyme-substrate complex. While separate, both enzyme and substrate force neighboring water molecules into an ordered shell. Binding of substrate to enzyme releases some of the ordered water, and the resulting increase in entropy provides a thermodynamic push toward formation of the enzyme-substrate complex.
Van der Waals interactions

van der Waals interactions arise when two uncharged atoms are brought very close together, their surrounding electron clouds influence each other. Random variations in the positions of the electrons around one nucleus may create a transient electric dipole, which induce a transient, opposite electric dipole in the nearby atom. The two dipoles weakly attract each other, bringing the two nuclei together.
Importance of weak interactions
All weak interactions can be said to be fundamentally electrostatic interactions. EXPLAIN
Ionic bonds, hydrogen bonds and van der Waals interaction depend on the unequal distribution of electrons, resulting in an unequal distribution of charge.
Explain how the following statement applies to biochemistry. Order can be generated by an increase in randomness.
The statement refers to the hydrophobic effect. Specific complicated biochemical structures can form, as a result of the increase in entropy from hydrophobic groups being removed from aqueous solution.
Ionization of water, weak acids & bases

Pure water is slightly ionized. The ionization of water is expressed by an equilibrium constant. The pH scale designates the H+ and OH- concentrations. Weak acids and bases have characteristic dissociation constants. Titration curves reveal the pKa of weak acids.
Ionization of water
Water is a neutral molecule with a very slight tendency to ionize. H2O H+ + OH Free protons (H+) dont actually exist, rather they exist as hydronium ions, H3O+. 2H2O H3O+ + OH For simplicity, however, we often represent these ions as H+.
Proton movement between water molecules

The proton of a hydronium ion can jump rapidly from one water molecule to another. Therefore, the mobility of H+ and OH- ions in solution are much higher than for other ions. Proton jumping is the reason for acid-base reactions being among the fastest.
Ionization of water
H2O H+ + OHThe ionization (dissociation) of water is described by the expression K = [H+] [OH-] (products) [H2O] (reactant) where K is the dissociation constant Because of the undissociated [H2O] is much larger than the concentrations of the component ions, it can be considered constant (unchanging), and incorporated into K to yield an expression for the ionization of water Kw. Kw = [H+] [OH-] The value of Kw, the ionization constant of water is 10-14 at 25C.
Ionization of water
If the ionization constant of water is 10-14 then the concentration of H+ in solution is 10-7 mol/L with an equivalent concentration 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 powers of 10, the pH scale can be used. pH = -log10[H+] = log 1 [H+] Eg: Human blood plasma has a [H+] of ~ 0.4 x 10-7 mol/L or 10-7.4 mol/L which gives a pH of 7.4
Ionization of water
The value where an equal amount of H+ and OH- ions are present is termed neutrality: at 25C the pH of pure water is 7.0. At this temperature pH values below 7.0 are acidic and above pH 7.0 are alkaline. Neutral solutions change with temperature, due to enhanced dissociation of water with increasing temperature. Always remember that the pH scale is logarithmic, and not a linear one. Thus a solution of pH 3.0 is not twice as acidic as a solution at pH 6.0 but 1000 times more acidic (ie: contains 1000 times more H+ ions).
http://www.authorstream.com/Presentation/ariedl-307910-ph-scalehydrogen-ions-science-technology-ppt-powerpoint/
pH scale
Acid-base chemistry
Acid a compound that acts as a proton donor in an aqueous solution. Base a compound that acts as a proton acceptor in an aqueous solution. Conjugate pair an acid together with its corresponding base. By the above definitions, an acid-base reaction can be written as HA + H2O H3O+ + A-
Acid-base chemistry
HA + H2O H3O+ + AAn acid (HA) reacts with a base (H2O) to form a conjugate base of the acid (A-) and the conjugate acid (H3O+). Eg: acetate ion (CH3COO-) is the conjugate base of acetic acid (CH3COOH) and the ammonium ion (NH4+) is the conjugate acid of NH3. The acid-base reaction is usually abbreviated to HA H+ + AThe participation of water in the reaction is implied. An alternative expression for a basic solution is HB+ H+ + B
Acid-base chemistry
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 expressed as a dissociation constant. K = [products] = [H3O+] [A-] [reactants] [HA] [H2O] In dilute solutions, the water concentration is essentially constant 55.5 M. Therefore, the term [H2O] is customarily combined with the dissociation constant, to take the form. For an acid At equilibrium HA = H+ + AKa = K [H2O] = [H+][A-] [HA]
Thus, the stronger the acid the greater the value of Ka.
Acid-base chemistry
Because the acid dissociation constants, like [H+] values are cumbersome to work with, they are transformed into pK values by the formula. pK = -logKa analogous to pH = -log [H+] = log 1 [H+]
Acids can be classified according to their relative strengths, that is, 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 involve H3O+, (OH-) and weak acids (and their conjugate bases).
Acid-base chemistry
Acid-base chemistry
Acid-base chemistry
The pH of a solution is determined by the relative concentration of acids and bases. The relationship between the pH of a solution and the concentrations of an acid and its conjugate base can easily be derived. Ka = [H+] [A-] [HA] rearrange [H+] = Ka [HA] [A-]
Take negative logs: -log [H+] = -log Ka -log[HA] [A-] or Thus, -log [H+] = -log Ka + log [A-] [HA] pH = pKa + log [A-] [HA]
Acid-base chemistry
The Henderson-Hasselbach Equation pH = pKa + log [A-] [HA] Relates the extent of ionisation of a weak acid (and base) to the pH of the solution. pH = pKa + log [conjugate base] [acid] This equation is of fundamental importance in preparing buffer solutions to control pH during biochemical reactions.
Acid-base chemistry
The ionisation characteristics of some of these compounds/groups actually controls the pH in cells and physiological fluids so pH varies only over a narrow range. In Blood the pH is regulated to stay in the range 7.35 7.45
Acid-base chemistry
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
Acid-base chemistry
The concentration of the acid in the original solution can be calculated from the volume and concentration of NaOH added and a titration curve plotted. At the midpoint of the titration, at which exactly 0.5 equivalent of NaOH has been added, [HA]=[A-] and pH=pKa.
Acid-base chemistry
The titration curves of these acids have the same shape, they are displaced along the pH axis because the three acids have different strengths. Acetic acid, with the highest Ka (lowest pKa) of the three, is the strongest (loses its proton most readily); it is already half dissociated at pH 4.76. Dihydrogen phosphate loses a proton less readily, being half dissociated at pH 6.86. Ammonium ion is the weakest acid of the three and does not become half dissociated until pH 9.25.
Buffering in biological solutions

Buffers are mixtures of weak acids and their conjugate bases. A simple expression relates pH, pKa, and buffer concentration (Henderson-Hasselbalch equation). Weak acids or bases buffer cells and tissues against pH changes.
Acid-base chemistry
Buffer are mixtures of weak acids and their conjugate bases. Buffers are aqueous systems that tend to resist changes in pH when small amounts of acids or base added. A mixture of equal concentration of acetic acid and acetate ion, found at the midpoint of the titration curve is a buffer system.
The secretions of the stomach have a [H+] of 0.01M. What is the pH?
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In the equilibrium reaction below, what is the effect of adding H+ in the form of HCl?
CH3COOH + H2O CH3COO- + H3O+ 1. The solution will become more basic 2. The equilibrium will shift to the right 3. The equilibrium will shift to the left 4. The chloride ions will react with acetic acid to form chloroacetic acid
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Protein structure & assembly
Diversity of proteins
Definition: A macromolecule composed of one or more polypeptide 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 polymers of molecular weights in the millions. Proteins occur in great variety and exhibit enormous diversity in biological function.
Enzymes Transport proteins Nutrient & storage proteins Contractile & motile proteins Structural proteins Defence proteins Regulatory proteins Specialized proteins

http://publications.nigms.nih.gov/structlife/chapter1.html
Enzymes
Definition: A biomolecule, either protein or RNA, that catalyzes a specific chemical reaction. Eg: - Triose phosphate isomerase - Serine proteases trypsin & chymotrypsin
Transport proteins
Myoglobin & Hemoglobin transport O2 from the lungs to peripheral tissues. Lipoproteins in blood plasma carry lipids to the liver and other tissues. Cell membrane proteins transport molecules and ions across membranes.
Transport proteins - Hemoglobin
Nutrient & storage proteins

Plant seeds store nutrient proteins needed for embryonic growth. Ovalbumin (egg white) and Caesin (milk) are examples of animal nutrient proteins. Other proteins store non-nutrient molecules and ions (eg: ferritin).
Contractile & motile proteins

Actin and Myosin are the key proteins involved in the movement of skeletal muscle. Tubulin microtubules are componentsof flagella and cilia which can move and propel cells.
Structural proteins
Collagen (see figure) is a component of cartilage and tendons. Elastin is found in ligaments and is a fibrous protein that stretches in two dimensions. Keratin makes up part of the fingernails and hair. Silk fibres and spider webs contain fibroin.
Defence proteins
Immunoglobulins are specialised proteins made in lymphocytes that recognise and neutralise foreign antigens (bacteria, viruses and proteins). Fibinogen & thrombin are involved in blood clotting to prevent blood loss. Snake venoms, bacterial toxins & toxin plant proteins all function to protection of the organism.
Regulatory proteins
Insulin is a hormone that regulates sugar metabolism. Repressors are proteins that regulate the transcription of specific genes.
Specialised proteins
There are any proteins which have specialised functions that are not easy to classify. Antifreeze protein from Antarctic fish which prevent their blood from freezing.
It is quite amazing that only 20 amino acids are able give rise to such an array of diversity.
Amino acids & peptide bonds

Amino acid: -amino-substituted carboxylic acids, the building blocks of proteins All amino acids have a carboxyl and amino group bonded to an -carbon. The -carbon also has a hydrogen and a side chain (Rgroup).
Amino acids
carbon = central C atom, with 4 different substituents (chiral): 1. -carboxyl group 2. -amino group 3. hydrogen atom 4. R group = side chain Each amino acid differs in the side chain which vary in charge, size, structure, water solubility and chemical properties. Peptide bond: An amide linkage between the -amino group of one amino acid and the -carboxylic group of another.
Chirality of amino acids

All amino acids with the exception of glycine are chiral and thus exist in L and D isomers. Only L-enantiomers are found in proteins.
Enantiomers (non-superimposable complete mirror images)

Chirality of amino acids

The formation of stable repeating substructures in proteins generally require their constituent amino acids to be of one stereochemical series. Cells are able to specifically synthesize the L isomer of amino acids because the active site of enzymes is asymmetric, causing the reactions they catalyze to be stereospecific.
All Amino Acids in naturally occurring proteins are L- isomers.
Acid-base properties of amino acids

-COOH group: a weak acid can DONATE its proton pKa ~ 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 base unshared pair of electrons on the :N neutral 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?
Amino acids
Amino acids
Nonpolar, aliphatic amino acids

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, stabilizing structure by means of hydrophobic interactions. Methionine is one of only 2 amino acids that contain sulfur. It contains a nonpolar thioester group in its side chain.
Nonpolar, aliphatic amino acids
Proline
Proline is a cyclic amino acid. Shares many of the properties of aliphatic amino acids. The rigid nature of proline makes the folding of proline into proteins difficult. Generally introduces a kink into polypeptide chain.
Polar, uncharged amino acids
Polar, uncharged amino acids

R groups of these animo acids are more soluble in water and 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.
Cysteine
The side chain can ionize at moderately high pH. It can form a covalently linked dimeric amino acid called a cystine in which two cysteine residues are joined to form a disulfide bond. Play a special role in structures by covalently links between different parts of a protein or different polypeptides. Disulfide linkages are strongly hydrophobic (nonpolar).
Disulfide bonds
Positively charged (basic) amino acids
Lysine & Arginine

The R groups carry positive charges and are strongly polar at pH 7.0. They are very hydrophilic and usually found on the exterior of proteins. Lysine has a secondary amino group on its aliphatic side chain. Arginine has a positively charged guanidino group.
Histidine
Histidine contains a imidazole group. Is the only common amino acid having an ionizable with a pKa near neutrality. In enzyme catalysed reactions a his residue facilitates the reaction by serving as a proton donor/acceptor.
Negatively charged (acidic) amino acids

R groups carry a net negative charge at pH 7.0. Like the positively charged amino acids they are very hydrophilic. Both aspartate and glutamate have a second carboxylic acid group.
Aromatic amino acids
Aromatic amino acids

The R groups in this class are relatively nonpolar and participate in hydrophobic interactions. The hydroxyl group of tyrosine is also important because of its ability to form H-bonds, and it is an important functional group in some enzymes. Tyrosine and tryptophan are significantly more polar than phenylalanine because of the tyrosine hydroxyl group and the tryptophan indole ring. Tryptophan, tyrosine and to a lesser extent phenylalanine absorb ultraviolet light.
Amino acid one & three letter codes

Alanine Arginine Asparagine Aspartic acid Cysteine Glutamic acid Glutamine Glycine Histidine Isoleucine Ala Arg Asn Asp Cys Glu Gln Gly His Ile A R N D C E Q G H I Leucine Lysine Methionine Phenylalanine Proline Serine Threonine Tryptophan Tyrosine Valine Leu Lys Met Phe Pro Ser Thr Trp Tyr Val L K M F P S T W Y V
You need to know

1. The structures of all 20 amino acids. 2. Their chemical & physical properties. 3. Their one letter & three letter codes. Properties of the 20 amino acids that occur in peptides and proteins are crucial to the structure and function of proteins Stereochemistry Relative hydrophobicity or polarity Hydrogen bonding properties Ionization properties Other chemical properties
How to learn amino acid structures

Why do we need to learn the amino acid structures?
Amino acids are the language of protein biochemistry. Without knowing these, it is impossible to think or talk sensibly about proteins and enzymes
Focus on Similarities not Differences

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

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.
COOH
+H 3N
C R
H R
The R group gives an amino acid its structural identity and, its unique biochemical properties.
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.
Glycine Alanine Phenylalanine Tyrosine
CH3
CH2
CH2
OH
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 on alanines methyl group. Tyrosine is formed by adding an OH group to the para position on the phenyl ring of phenylalanine.

The acidic amino acids have negative () charges in their R group. There are two, aspartic acid and glutamic acid. Note their similarity. Glutamic acid has one more CH2 group. Note that both have a COO group which gives the negative charge.
Aspartic acid Glutamic Acid Asparagine Glutamine
CH2 COO Aspartate
CH2 CH2 COO Glutamate
CH2 COO C=O NH2
CH2 CH2 C=O COO NH2
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 and glutamate. The amide derivatives of aspartate and glutamate are asparagine and glutamine.

The positively (+) charged amino acids are represented by lysine, arginine and histidine.
Lysine Arginine Histidine
CH2 CH2 CH2 CH2 NH3+

Epsilon amino
+H 2N=C
CH2 CH2 CH2 NH NH2 HN
CH2
NH+
Imidazole
Guanidinium
Each is characterized by a (+) N in the R group. For lysine this group is called the epsilon amino group. In arginine it is the guanidinium group and for histidine it is the imidazole group.

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 serine with a methyl group. In Cysteine, the O in serine has been replaced Cysteine with an S. Serine Threonine Methionine
CH2OH
H-C-OH CH3
CH2SH
CH2 CH2 S CH3
Methionine appears to combine cysteine with threonine. The name tells you methionine has a sulfur (thio) and a methyl group in the structure.

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 is arranged as the letter V. Leucine and isoleucine both have a 4 carbon R group. Leucine resembles valine but with a -CH2 before the V. Isoleucines side chain resembles the letter L. To distinguish these amino acids, focus only on the branched chains in the R structure. Valine and leucine have only methyl groups, whereas isoleucines branches are one methyl and one ethyl group
Valine Leucine Isoleucine
C C C C
C C C
C C C C Ethyl group

Tryptophan and Proline Tryptophan is unique in having an indole ring attached to the core via a CH2 group. Proline also has a ring, but this ring is aliphatic and saturated. Note proline does not have a core structure. This is because the alpha amino group is incorporated into the ring.
Tryptophan Proline
CH2
H2C H2C N H
CH2 C H COO
N H Indole
http://www.biology.arizona.edu/biochemistry
Modified amino acids

There are a number of modified amino acids which are formed from the common amino acids. Examples: 4-hydroxyproline (cell walls, collagen) 5-hydroxylysine (collagen) 6-N-methyllysine (myosin) -carboxyglutamate (prothrombin) selenocysteine
4-hydroxyproline
Example: collagen, a fibrous protein of connective tissue.
5-hydroxylysine
Example: collagen, a fibrous protein of connective tissue.
6-N-Methyllysine
Example: a constituent of myosin, a contractile protein of the muscle.
-Carboxyglutamate
Example: found in the blood clotting protein prothrombin and in certain Ca2+ binding proteins.
Selenocysteine
Is introduced during protein synthesis rather than created through a post-synthetic modification.

-COOH group: a weak acid can DONATE its proton pKa ~ 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 base unshared pair of electrons on the :N neutral 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 the terminal groups on a chain of Amino Acids, i.e., a peptide or 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 the carboxyl group largely deprotonated (COO-) forming a zwitterion.

-Amino Acids, Ionization
-carboxyl group -amino group
Berg et al., Fig. 2-6

Amino acids titration curves

Two distinct stages corresponding to the deprotonation of carboxy group and the amide group. At low pH glycine is fully protonated. At the midpoint of this part of the titration (point of inflection) the pH = pKa (pK1). As the titration continues another inflection point is reached. At this point removal of the first proton is complete. The second half of the titration corresponds to the removal of the proton from the amide.
Amino acids titration curves important points

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 either side of the pKa. The relationship between net electric charge and the pH of the solution can also be derived from the titration curve. So at pH 5.97, glycine is present in its dipolar form, fully ionized but with no net electrical charge. This point is called the Isoelectric point or Isoelectric pH. So at a pH < pI glycine has a net + charge & at a pH > pI glycine has a net - charge
Ionization of amino acids

The side chains of each amino acid are also ionisible and each group has a specific pKa. At pH > pKa the proton tends to be off. At pH < pKa the proton tends to be on. The average pKa for an amino acid approximates the isoelectric point (pI), where there is no nett charge. As pH increases above the pI the net charge becomes negative. As pH decreases below the pI the net charge becomes positive. When the amino acids are incorporated into proteins only the charges on the side chains remain.
Titration of Glutamate
Titration of Histidine
Why is the His side chain (imidazole group) called basic if the predominant form at pH 7 is unprotonated?
Why is the His side chain (imidazole group) called basic if the predominant form at pH 7 is unprotonated?
Questions on amino acids

Which of the 20 amino acids is achiral (has no asymmetric C)? Which aliphatic Amino Acid has 2 chiral centers? 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 to dissociate 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. can they gain or lose a proton? Why or why not?

Module 1 - Topic 1 - The Chemistry of Life

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Welcome to 1002BPS Structural Biochemistry

Biochemistry: The Chemistry of Life

1002BPS STRUCTURAL BIOCHEMISTRY MODULE 1

1002BPS Structural Biochemistry

Teaching team member: Dr Ian Cock

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Structural Biochemistry: Modules 1-3

Module 2 (Lehninger pages 113-131, 135-140)

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Structural Biochemistry: Modules 1

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Weak interactions in aqueous solutions

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Hydrogen bonding - unusual properties of H20

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The structure of H20

Hydrogen bonding between water molecules

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Hydrogen bonding between water molecules

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Hydrogen bonding of ice

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Hydrogen bonding between water molecules

Examples of hydrogen bond acceptors & donors

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Some biologically important hydrogen bonds

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Examples of hydrogen bond acceptors & donors

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Polar, non-polar & amphipathic biomolecules

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Positive S Increase in entropy

H = change in Enthalpy Heat produced or absorbed

S = change in Entropy Change in order or randomness