Chapter 1 1) Biological Molecules a) Only a small subset of the known elements are found in living systems i) Most abundant- C, N, O, and H ii) Less

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1 Chapter 1 1) Biological Molecules a) Only a small subset of the known elements are found in living systems i) Most abundant- C, N, O, and H ii) Less abundant- Ca, P, K, S, Cl, Na, and Mg b) Cells contain only 4 major types of biomolecules i) Amino Acids (1) Contain an Amino group (-NH2) and a Carboxylic acid group (-COOH) (2) Under physiological conditions, these groups are actually ionized (-NH3 + ) and (-COO - ) ii) Carbohydrates (1) Simple carbohydrates have the molecular formula (CH2O)n (2) Forms cyclic structure in solution iii) Nucleotides (1) Contains a 5-carbon sugar, a nitrogen-containing ring, and one or more phosphate groups. (2) The most common nucleotides are mono, di, and triphosphates containing the nitrogenous ring compounds (or bases ) adenine, cytosine, guanine, thymine, and uracil. iv) Lipids (1) Can not be described by a single structural formula because they are a diverse collection of molecules (2) All have in common a tendency to be poorly soluble in water because bulk of structure is hydrocarbon like. c) 3 Major biological polymers i) Proteins (1) Polymers of Amino Acids are called Polypeptides or Proteins (2) 20 different amino acids serve as building blocks for proteins (3) Amino acid residues are linked to each other by amide bonds called peptide bonds (4) Are classified as the most structurally variable and most functionally versatile of all the biopolymers. ii) Nucleic Acids (1) Polymers of nucleotides are termed polynucleotides are nucleic acids better known as DNA and RNA (2) Polymerized from just 4 nucleotides (3) Polymerization involves the phosphate and sugar groups of the nucleotides, which become linked by phosphodiester bonds (4) Because of rigid structure, genetic information is easily transmitted iii) Polysaccharides (1) Most polysaccharides in cells are homogenous polymers (2) Due to homogenous polymers, preforms essential cell functions by serving as fuel storing molecules and providing structural support (3) Residues are linked by glycosidic bonds

2 Biopolymer Encode Information Carry out metabolic reactions Store Energy Support Cellular structures Proteins X Major Minor Major Nucleic Acids Major Minor X Minor Polysaccharides Minor X Major Major 2) Energy and Metabolism a) Enthalpy and Entropy are components or free energy i) Enthalpy (H)- is taken to be equivalent to the heat content of the system ii) Entropy (S)- is a measure of how the energy is dispersed within that system. Disorder or randomness (1) Temperature is a coefficient of entropy because entropy caries with temp., entropy increases when warmed because more thermal energy has been dispersed within it. b) ΔG is less than zero for a spontaneous process i) In order for a process to occur, the overall change in free energy (ΔG) must be negative. Free energy of products must be less than free energy of reactants. ii) A->B (ΔG>0) (Nonspontaneous) iii) A->B (ΔG<0) (Spontaneous) iv) ΔG does not govern the rate of a reaction, only if a reaction will occur v) A reaction that occurs with a decrease in enthalpy and an increase in entropy is spontaneous at all temperatures c) Life is thermodynamically possible i) Cells couple unfavorable metabolic processes with favorable so that the net change in free energy is negative ~Learning Objectives~ Know that only a small subset of the known elements are found in living systems o Know the most abundant: C, N, O, H Know that living organisms are carbon-based o Closely related to organic chemistry Be able to recognize common functional groups in biological molecules Know the four major types of biomolecules and their general structures o Amino acids (polarity determined by R-Side chain) o Carbohydrates o Nucleotides (5 C sugar, Nitrogenous Base, Phosphates) o Lipids (Amphipathic, mostly nonpolar) Know the three types of polymers (involve condensation of water) o Proteins Polymers of amino acids joined by peptide bonds (Carbonyl group bound to amine) o Nucleic acids DNA and RNA Polymers of nucleotides joined by phosphodiester bonds o Polysaccharides o Polymers of carbohydrates joined by glycosidic bonds Know which type of biological molecule does not form polymers and why o Lipids (lack common function groups=cant really string them together)

3 Know the definition Gibbs free energy (G, J/mol) Energy relevant to biochemical systems (portion of energy change available to do work) Understand the principle of enthalpy (H, J/mol) and how it relates to G Total energy or Heat content of system Understand the principle of entropy (S, J/K mol) and how it relates to G Measure of the dispersion of the energy of the system Measure of disorder or randomness Understand how temperature (T, K) relates to entropy and G Absolute temperature in Kelvin Know the equation: G = H - (T S) and how to use it appropriately Under what conditions would G always be a negative value? Given that building living systems results in a decrease in entropy, what makes life possible from a thermodynamic perspective? Know the principle of spontaneity and how it relates to G G > 0, nonspontaneous or endergonic G < 0, spontaneous or exergonic Measure of equilibrium NOT speed Be able to recognize or determine if a reaction or process is spontaneous Understand the principle of coupling reactions Spontaneous biochemical reactions can be coupled with unfavorable reactions to net negative change in free energy Know that many biochemical reactions involve oxidations and reductions Compounds are oxidized when electrons are extracted Compounds are reduced when electrons are accepted These are called redox reactions because both occur simultaneously Know how to recognize oxidations and reductions of carbon (and other) compounds Metabolic reactions are catalyzed by enzymes Mostly protein some RNA Know the three domains of life (Eukarya, archea, Bacteria) How are they classified (based on rrna sequence)? Know what defines prokaryotes Lack nucleus and internal organelles Archaea Often inhabit extreme environments Similar in structure to bacteria Bacteria Know what defines eukaryotes Most often larger than prokaryotic cells Contain nucleus and intracellular compartments Include microbes and macroscopic plants and animals Unicellular or multicellular

4 Chapter 2 1) Water molecules form hydrogen bonds a) Characteristics i) The human body is about 60% by weight water ii) The central oxygen atom forms covalent bonds with the two hydrogen atoms iii) Molecule has a tetrahedral geometry iv) Water molecules are polar; that is, it has an uneven distribution of charge v) Hydrogen Bonding (1) Hydrogen bond is now known to have some covalent character (2) 4 hydrogen bond potential for each water molecule (a) 2 hydrogen atoms to donate to a hydrogen bond (b) 2 pairs of unshared electrons that can accept a hydrogen bond (3) Water can form hydrogen bonds not just with other water molecules but with a wide variety of other compounds that bear N-, O-, or S- containing functional groups. (a) Likewise, these functional groups can form hydrogen bonds among themselves (ex. DNA) b) Hydrogen bonds are one type of electrostatic force i) Non-Covalent Interactions (1) Ionic interactions (a) Electrostatic interactions between charged groups (ex. COO - & - NH3 + ) (b) Intermediate in strength between covalent bonds and hydrogen bonds (2) Hydrogen Bond (a) Despite partial covalent nature, are classified as a type of electrostatic interaction (b) Longer and hence weaker than a covalent OH bond (3) Van der Waals Interaction (a) Occur between particles that are polar but not actually charges (b) Weaker than hydrogen bonds (c) Dipole-Dipole Interactions (i) Interaction between two strongly polar groups (d) London Dispersion Forces (i) Occur between nonpolar molecules as a result of small fluctuations in their distribution c) Water dissolves many compounds i) Water has a high dielectric constant: measure of a solvents ability to diminish the electrostatic attractions between the two ions (1) The dissolved particle is called the solute and is said to be solvated or hydrated 2) The hydrophobic effect a) Non-Polar Substances (Long chains of Hydrocarbons) i) Do not dissolve but form a separate phase

5 ii) Why is it thermodynamically unfavorable to dissolve a non-polar substance in water? (1) Depends heavily on the entropy (ΔS) (a) This is because when a hydrophobic molecule is hydrated, it becomes surrounded by a layer of water molecules that cannot participate in normal hydrogen bonding but instead must align themselves so that their polar ends are not orientated toward the nonpolar solute (i) This constraint on the structure of water rep. a loss of entropy iii) Aggregation of nonpolar molecules in water (1) Individual hydration of dispersed non polar molecules decreases the entropy of the system because the hydrating water molecules are not free to form hydrogen bonds (2) Aggregation of nonpolar molecules increases the entropy of the system, since the number of water molecules to hydrate the aggregated solutes is less than the number of water molecules required to hydrate the individual dispersed molecules b) Amphiphilic molecules experience both hydrophilic interactions and the hydrophobic effect (1) Amphipathic: Molecules with both hydrophobic and hydrophilic portions (2) What happens when these molecules are added to water? (a) The polar groups of amphiphiles orient themselves toward the solvent molecules and are therefore hydrated, while the nonpolar groups tend to aggregate due to the hydrophobic effect (i) Micelle: a particle with a solvated surface and a hydrophobic core 1. Formed by one tail lipids (3) Bilayers (a) Amphiphilic lipids that provide the structural basis of biological membranes form these two layer sheets (b) Thermodynamically favored because the hydrogen bonding capacity of the polar head groups is satisfied through interactions with solvent water molecules, and the non polar tails are sequestered from the solvent (c) Formed by two tailed lipids c) The hydrophobic core of a lipid bilayer is a barrier to diffusion (1) To eliminate solvent exposed edges, a lipid bilayer tends to close up and from a vesicle (2) Diffusion (a) Movement Down concentration gradient is a spontaneous process driven by an increase in entropy (b) A bilayer can prevent this diffusion (c) Intracellular- Potassium (d) Extracellular- Sodium (e)

6 3) Acid-Base Chemistry a) Characteristics i) H + can be visualized as combining with a water molecules to produce a hydronium ions (H3O + ) (1) H + is probably delocalized, so it probably exists as part of a larger, fleeting structure (2) Protons due not remain associated with a single water molecules, but jump and relay through a hydrogen bond network of water molecules known as Proton Jumping b) [H + ] and [OH - ] are inversely related i) Pure water has only a slight tendency to ionize (1) Kw = Kw = [H + ][OH ] ii) The hydrogen ion concentration is expressed as ph (1) ph=-log[h + ] c) A pk value describes an acids tendency to ionize i) The larger the value of Ka, the more likely it is to ionize; that is, the greater its tendency to donate a proton to water ii) The larger an acids Ka, the smaller its pk and the greater its strength as an acid iii) Polyprotic acids (1) Has a pk for each dissociation (2) The first proton dissociates with the lowest pk value. Subsequent protons are less likely to dissociate and so have higher pk values d) The ph of a solution of acid is related to the pk i) Henderson-Hassel Balch Equation ii) ph = pk + log [A ] [HA] iii) When the ph of a solution of acid is equal to the pk of that acid, then the acid is half dissociated ; that is exactly half of the molecules are in the protonated HA form and half are in the deprotonated A - form iv) ph<pk = Mostly protonated v) ph>pk = Mostly deprotonated 4) Buffers a) Weak Acid/conjugate base system (HA/A-) acts as a buffer b) At the midpoint of a titration, exactly half of the protons have dissociated, so [HA]=[A-] and ph=pk c) The effective buffering capacity of an acid is generally taken to be within one ph unit of its pk ~Learning Objectives~ Understand the basic principles of covalent bonds (two atoms are sharing valence or outer shell electrons) Understand the basic principles of hydrogen bonds Electronegative element covalently bonded to H atom and electrostatically attracted to 2nd H atom What contributes to a strong H-bond versus a weak one? (Linear alignment=stronger/ Skewed bond=weaker) Understand the molecular structure of water What makes it a polar molecule? (Dipole moment in molecule due to electronegative oxygen) Understand the formation of H-bonds in water in liquid and solid form (1 H2O can H-Bond with 4 others What contributes to the surface tension of water? (Highly cohesive)(weight of body is less than strength of interactions of water molecules causing a bug to sit on water) o Be able to recognize H-bond donors and acceptors

7 Know the relative strengths of the different types of bonds H-bonds 3 Ionic bonds 2 Covalent bonds 1 van der Waals (dipole-dipole [interaction between 2 polar groups/ 2 dipoles must be present] and London dispersion forces[interaction between to non-polar molecules]) 4 Be able to determine the type of intermolecular interactions involved for a given compound Know how to rank melting or boiling points of compounds Based on nature and strength of intermolecular forces Understand concept of dielectric constant Measure of polarity Understand the principles of the hydrophobic effect Based mainly on changes in entropy How this drives spontaneous associations based on polarity How lipids can associate as micelles or membranes and what determines the nature of their association in an aqueous environment When lipids are scatter, water molecules are ordered around molecules resulting in a large decrease in entropy When lipids cluster, water molecules are not as ordered around molecules resulting in low decrease in entropy (Comparatively speaking there is an increase in entropy) Benefits of lipid associations into membranes What types of molecules can pass thru the lipid bilayer Understand Movement of protons in water Principles of spontaneous dissociation of water Ionization constant of water Be able to use ionization constant of water to determine concentration of either H+ or OH- Understand principles of ph scale and how to determine ph from [H+] and vice versa Understand concept of acid dissociation constant and pk value ph at which group is ½ ionized Be able to calculate pka from Ka and vice versa Be able to recognize a weak acid/conjugate base pair and distinguish between them Be able to determine if group will be charged or uncharged at given ph Based on pk value Be able to use Henderson-Hasselbach equation in acid-base chemistry problems Understand effects of adding weak acid or base to water Only partial dissociation Understand effect of adding strong to weak acid and strong to weak base

8 Chapter 4 1) Proteins are chains of amino acids a) Hydrophobic Amino Acids i) The hydrophobic amino acids have essentially non polar side chains that interact very weakly or not at all with water ii) These amino acids are almost always located in the interior of the molecule iii) Because they lack reactive functional groups, the do not participate in mediating chemical reactions b) Polar Amino Acids i) These side chains can interact with water because they contain hydrogenbonding groups ii) These amino acids can be found on the solvent exposed surface of a protein c) The charged amino acids i) Four amino acids have side chains that are virtually always charged under physiological conditions ii) These side chains are usually located on the proteins surface, where their charged groups can be surrounded by water molecules d) Peptide Bonds i) Polymerization involves the condensation of the carboxylate group of one amino acid with the amino group of another (1) Amide Bond=Peptide Bond (2) Peptide Bonds can be broken, or hydrolyzed, by the action of exo or endopeptidases (3) Except for the 2 terminals, the charged amino and carboxylate groups of each amino acid are eliminated in forming peptide bonds. (a) The electrostatic properties of the polypeptide therefor depend on the identities of the side chains e) First level of protein structure i) Sequence of amino acids in a polypeptide 2) Secondary structure: The Conformation of the peptide group a) Rotation is limited i) No rotation around the C-N Bond (Peptide bond) (1) Electrons are delocalized and have 2 resonance forms (a) Partial double bond character (2) The amino acid residues can therefor be said to be a planar peptide ii) Steric hindrance of R groups in residues prevents rotation iii) Hydrogen Bond requirements also prevent rotation as specific linear bonding is optimal and required b) Groups involved in peptide bonds are strongly polar, with a tendency to form hydrogen bonds i) Amide backbone group are hydrogen bond donors ii) The carbonyl oxygen are hydrogen bond acceptors iii) Under physiological conditions, the polypeptide chain folds so that it can satisfy as many as these hydrogen bond requirements as possible

9 iv) Polypeptide backbone must adopt a conformation (2 nd structure) that minimizes steric strain v) Regular Secondary Structures: (1) α-helix [Twisted backbone conformation] (a) In this type of structure, the polypeptide backbone twists into a right handed helix (b) There are 3.6 residues per turn of the helix (c) The carbonyl oxygen of each residue forms a hydrogen bond with the backbone NH group 4 residues ahead (d) Side chains extend outward from the helix (2) β-sheet [Multiple polypeptide strains] (a) Aligned strands of polypeptide whose hydrogen bonding requirements are met by bonding between neighboring strands (b) 2 arrangements: (i) Parallel β Sheet: Neighboring stands run in same direction (ii) Anti-Parallel β Sheet: Neighboring strands run in opposite direction vi) Proteins also contain irregular secondary structures (1) In every protein, elements of secondary structure are linked together by peptide loops of various sizes (2) Usually loops that link β-sheets and α-helices consist of residues with irregular secondary structures (a) The polypeptide does not adopt a definite secondary structure in which successive residues have the same backbone conformation (i) Ex: the final turn of some alpha helices become stretched out (b) Irregular does not mean disordered (3) Most proteins contain a combination of regular and irregular secondary structures 3) Tertiary structure and protein stability a) Include its regular and irregular secondary structure b) The protein comprises a hydrophilic surface and a hydrophobic core i) Proteins have hydrophobic cores (1) Domain: a polypeptide segment that has folded into a single structural unit with a hydrophobic core (a) Core of domain is typically rich in regular secondary structure. Because the α-helices and β-sheets, which are internally hydrogenbonded, minimizes the hydrophillicity of the polar back bone groups (b) Irregular secondary structures are more often found on the surface of the protein (2) The greater a residues hydrophobicity, the more likely it is to be located in the proteins interior (a) Hydrophobic residues such as Phe and Met are almost always buried (b) Polar side chains, like hydrogen bonding backbone groups, can participate in hydrogen bonding in the interior, which help

10 neutralize their polarity and allows them to be buried in nonpolar environments (i) Charged interior residue=next to opposite charge residue= Ion Pair ii) Protein structures are stabilized mainly by the hydrophobic effect (1) The fully folded conformation of a protein is only marginally more stable than its unfolded form (2) The largest force governing protein structure is the hydrophobic effect (a) Causes nonpolar groups to aggregate in order to minimize their contact with water (b) Driven by increase in entropy, otherwise water would have to order themselves around each hydrophobic group (c) This arrangement stabilizes the folded polypeptide backbone, since unfolding it or extending it would expose the hydrophobic side chains to the solvent (3) Hydrogen bonding itself is not a major determinant of protein stability (i) In an unfolded protein polar groups could just as easy from energetically equivalent hydrogen bonds with water molecules iii) Cross-links help stabilize proteins (1) Ion pairs (a) Forms from oppositely side chains of N- and C- terminus (b) Does not contribute much to protein stability (i) Favorable free energy of the electrostatic interaction is offset by the loss of entropy when side chains become fixed (2) Disulfide bonds (a) Not essential fro stabilizing proteins (i) Experiments show that even when Cys residues of certain proteins are chemically blocked, the proteins may still fold and function normally (b) Rare in intracellular proteins, since the cytoplasm is a reducing environment. They are more plentiful in proteins that are secreted to an extracellular (oxidizing) environment. (3) Zinc-Fingers (a) Zinc is an ideal metal for stabilizing small proteins (i) Protein domains small in size are too small to assume a stable tertiary structure without a metal ion cross link (b) It can interact with ligands (c) Has only one oxidation state iv) Protein folding begins with the formation of secondary structures (1) Protein folding is not a random process (a) The protein does not just happen upon its most stable tertiary structure (b) Process: (i) Small elements of secondary structure form first

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