Biochem I Final Exam

Which types of covalent bonds are important in biochemistry (only partially covered?

- regular covalent bonds

- coordination bonds

Which types of bonds can carbon, nitrogen, hydrogen, and oxygen form with each other?

covalent bonds

which types of bonds can oxygen and nitrogen form with metals such as Fe2+, Co2+, and Zn2+?

coordination bonds

how many coordination bonds does Fe+2 have?

6 coordination bonds arranged in an octahedral

how many coordination bonds does Zn+2 have?

4 coordination bonds arranged in a tetrahedral

Which types of bonds allow free rotation around the bond axis, which do not?

single bonds allow rotation

double bonds DO NOT allow rotation

How does electronegativity influence the charge distribution between covalently bound atoms?

the electrons are not equally distributed between the bonding partners, electronegative atoms pull electrons towards them

You should be able to rank O, N, C, S and H according to their relative electronegativity.

O > N > S = C > H

What is the general geometry of a ligand bound via single bonds to a carbon, nitrogen, or oxygen atom? What is the geometry if one of the bonds is a double bond? Explain your answer based on sp3 versus sp2 hybridization.

• single bond = arranged in a tetrahedral (bc of sp3 hybridized orbitals)

• double bond = arranged in planar trigonal (bc of sp2 hybridized orbitals)

What is the difference between regular covalent bonds and coordination bonds in terms of the origin of electrons forming the bond?

• covalent bonds: SHARE electrons

• coordination bonds: BOTH electrons are donated by the same atom

What is the meaning of the terms "configuration" and "conformation"?

configuration: stereoisomers (cis or trans), not possible to use rotation to superimpose one form on the other

conformation: different geometric arrangements generated by rotation around a single bond... no bonds need to be broken to change conformations

You should be able to recognize a "cis" and a "trans" configuration.

cis: R groups on same side

trans: R groups on opposite sides

List four types of non-covalent interactions that are important in biochemistry.

1. H-bond

2. Ionic interactions

3. Van der Waals

4. hydrophobic interactions

List seven elementary interactions:

1. charge-charge

2. charge-dipole

3. dipole-dipole

4. charged-induced dipole

5. dipole-induced dipole

6. dispersion

7. van der waals repulsion

describe how electrostatic interactions, hydrogen bonds and van der Waals interactions are composed of more elementary interactions

• two full charges can deform each other to induce dipoles in each other

• a charge can further deform a permanent dipole and induce an even stronger dipole, etc.

What is the distance dependence of the Coulomb force? Is it always attractive?

• attractive interaction decreases with distance

• coulomb force is always attractive, EXCEPT for van der waals forces

What are the requirements for the formation of a hydrogen bond?

• H-bond donor (usually strongly electronegative)

• H-bond acceptor (lone pair e-)

Hydrogen bonds are made up of which more elementary interactions?

• charged H-bond donors: contain charge-dipole, dipole-dipole, charge-induced dipole, dipole-induced dipole, dispersion, and van der waals repulsion

• uncharged H-bond acceptors: contains dipole-dipole, dipole-induced dipole, dispersion, and van der waals repulsion

The hydrogen bond and the van der Waals interaction are made up of which more elementary interactions?

it is composed of dispersion and van der waals

dispersion is attractive until the electron shells crash, leading to repulsion

How rapidly is the van der Waals attraction (repulsion) potential falling off with distance?

about -1/r^6

Which attractive elementary non-covalent interaction has the longest range, which the shortest?

• longest: charge-charge

• shortest: van der waals

Which attractive elementary non-covalent interaction is the most repulsive and least repulsive?

• van der waals is the most repulsive

• charge-charge is the least repulsive

What is the most common elementary non-covalent interaction in the interior of proteins?

hydrogen bonding

What is the relative strengths of non-covalent interactions as compared to covalent bonds?

covalent bonds are MUCH stronger than non-covalent

What is the weakest non-covalent interaction (even at the optimal distance)?

van der waals

Why does water have a dipole moment? In which direction is it pointing?

• oxygen is more electronegative than hydrogen

• the electron pairs on oxygen point away from hydrogens

Why are the properties of water important for biochemistry?

• water is a universal solvent

• properties of water determine folding of biological macromolecules

• properties of water are at the core of the compartmentalization of biochemical reactions by membranes

• water participates in many biochemical reactions

• our bodies consist of ~60% water

List seven properties of water that are unique compared with hydrides of elements other than oxygen.

1. water is a liquid @ room temp

2. water has a high boiling point

3. a high melting point

4. high heat capacity

5. high surface tension

6. high dielectric constant

7. liquid water has a higher density than ice

What is at the root of many of water's unique properties?

the ability to H-bond with each other

Why is water a good solvent for many molecules?

• water is both an H-bond donor and acceptor

• 4 H-bonds can be formed per molecule of H2O

How does water interact with different molecules?

• H-bonding in water is cooperative

• H-bonded water is H-bond donor and acceptor

• dipoles further induce neighboring dipoles

• more polarization

• stronger H-bonds

What determines solubility of molecules in water (very important)?

• ability to H-bond

• if it is polar/hydrophilic

• think of "like dissolves like"

What is the geometric arrangement of water molecules in ice?

tetrahedral

How does is the hydrogen bonding pattern of water change during melting?

• H-bonds are constantly being broken and formed

• during melting, only ~2 H-bonds per molecule remain allowing for closer packing

What is the meaning of the thermodynamic terms ∆G, ∆H, and ∆S?

∆G: Gibbs free energy

∆H: enthalpy

∆S: entropy (disorder)

How do the thermodynamic values change during melting?

∆G= -

∆H= +

∆S= +

Is melting driven by ∆H or ∆S?

∆S

Define the terms "hydrophilic" and hydrophobic"

• hydrophilic: dissolves in water (polar)

• hydrophobic: repel water (non-poalr)

What is an amphipathic molecule (name a biological example)?

• possess both polar and non-polar groups

• ex: fatty acids (phenylalanine)

Explain the hydrophobic interaction in terms of water dynamics. (What is the structure of water at hydrophobic surfaces, and how does this change when hydrophobic surfaces begin to contact each other?)

• when lipids are dispersed in H2O, water molecules are forced to be highly ordered around these lipid groups (∆S<0 unfavorable)

• when non-polar groups move together, there is less contact w/water (less water molecules are forced to be ordered)

• water molecules surrounding the hydrophobic surface are released into their bulk phase (∆S>0 favorable)

• this is a favorable situation

Describe in general terms the role of water molecules in substrate-enzyme or drug-receptor binding.

• ordered water interacts with substrate and enzyme

• disordered water is displaced by enzyme-substrate interaction

How is water ionized?

• water is a base and acid

• H3O+ and OH-

How is the "ionic product of water" defined? What is its value?

"ion product of water," describes the extent to which water molecules spontaneously ionize into H₃O⁺ and OH⁻

1.0×10^−14

How are pH and pOH related?

pH + pOH = 14

what is pOH?

measure of the OH- concentration in a solution

• -log[OH-]

what is pH?

hydrogen ion concentration

• -log[H+]

What is the difference between a strong acid/base and a weak acid/base?

• strong: dissociate completely

• weak: do not dissociate completely

What is the definition of pKa?

the pH at which A- and equal to HA = -log[Ka]

pH < pKa

protonated

pH > pKa

deprotonated

Write down how a conjugate acid is converted to a conjugate base

HA ⇌ A− + H+

Henderson-Hasselbalch equation

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

What is the relationship between a buffer's pKa and the pH range for which a buffer can be used?

a good buffer range would be +/- 1 pKa of the pH we want to maintain

How does the pKa of a strong acid compare with that of a weaker one? Make the same comparison for bases.

• smaller pKa = stronger acid, weaker base

• larger pKa = weaker acid, stronger base

Does the pKa of a compound tell you if it is an acid or a base?

no, it tells you how easy a proton is lost or gained

Can bases have a pKa > 7 and can have bases have a pKa < 7?

• pKa > 7 indicates that the substance is a weak acid

• pKa < 7 indicates that the substance is an acidic compound

Name two important biological buffer systems

• in cells: phosphate

• in blood: the bicarbonate/CO2 system

Is the pKa of carbonic acid close to physiological pH?

no, it is too far from the physiological pH

Why is the bicarbonate / CO2 system still suitable as a biological buffer system?

during breathing, CO2 is removed from the blood and the equilibrium is shifted left, removing protons generated during metabolism

What is the general structure of an amino acid (structure of the head group).

• α-carbon (carboxyl and amino attached)

• side chain R

• carboxyl group

• amino group

What is a "Zwitterion"?

a neutral molecule with both positive and negative charges

What are enantiomers?

isomers that are mirror images of each other

Which of two possible stereoisomers occur naturally in proteins?

L-amino acids

What is the meaning of the hydropathy index?

hydrophobicity

• > 1 = more hydrophobic

• < 1 = less hydrophobic

Which amino acid side chains have positive, which have negative hydropathy indices?

positive:

- alanine

- valine

- leucine

- isoleucine

- methionine

- phenylalanine

- cysteine

negative:

- glycine

- proline

- tyrosine

- tryptophan

- serine

- threonine

- asparagine

- glutamine

- lysine

- histidine

- arginine

- aspartate

- glutamate

Which amino acid has a cyclic (non-aromatic) structure?

- histidine

- proline

Which "amino acid" is actually an "imino acid"?

proline

Which amino acid introduces "kinks" in a polypeptide chain?

proline

Which amino acid can form disulfide bridges between and within polypeptide chains?

cysteine

What is the difference between cysteine and cystine?

cystine is two cysteines linked by a disulfide bond

Which amino acids have a side chain pKa closest to the physiological pH (name two)?

histidine and cysteine

Why is the pKa of the a-carboxylic and the a-amino group of glycine lower than that of acetic acid and methylamine, respectively?

• for acetic acid: oppositely charged groups lower the pKa by stabilizing the zwitterion

• for methylamine: electronegative oxygen atoms in the carboxyl group pull e- away from the amino group, lowering the pKa

Which functional groups of amino acids contribute to forming a peptide bond?

α-carboxylic acid + α-amino groups --> condensation water

Are peptide bonds in water thermodynamically stable?

no

What is the reason for the persistence of peptide bonds in water?

due to the high activation energy of cleavage

What resonance structures exist in peptide backbones, which bonds are flexible (allow rotation around the bond axis), which are not (pick out of these: N-Ca, Ca-C, C-N)? What is the reason for differences of flexibility?

flexible: Cα-C and N-Cα

not flexible: peptide bond (C-N)

• peptide bonds are not flexible because the resonance gives double bond character

The peptide bond is "kinetically stable". What does that mean?

a very high activation energy exists in the reverse hydrolysis reaction. Therefore, under normal physiological conditions, not enough energy exists to break the peptide bond via this hydrolysis reaction

What is a peptide, oligopeptide, polypeptide, protein?

• peptide: short chain of amino acids

• oligopeptide: peptide: only a few amino acids are linked together

• polypeptide: ~5o amino acids linked together

• proteins: polypeptides with additional structural features

What are the names of the ends of a peptide? In which direction is the sequence of peptides and proteins read?

one end: free amino group, amino-terminal end, N-terminal end, N-terminus, amino-terminus

other end: free carboxyl group, carboxy-terminal end, C-terminal end, C-terminus, carboxy-terminus

read:

start (amino-terminus) to end (carboxy-terminus)

What is the meaning of phi (ϕ) and psi (ψ) angles? How many and which atoms in a protein backbone are needed to define each of these angles?

• they define the structure of peptide and protein backbones and describe rotation around the two bonds connecting Cα

• N-Cα represents phi

• Cα-C represents: psi

What are the ϕ- and ψ-angles of a fully extended conformation?

180°

What is a Ramachandran Plot?

A plot of the angles of phi and psi angles

What is the meaning of the term "primary structure" of a protein?

• amino acid sequence

• covalent bonds

What is the meaning of the term "protein secondary structure"?

used to describe simple (highly regular) and commonly found structural features of proteins

Which parts of a polypeptide chain mainly contribute to the establishment and stability of secondary structure?

H-bonds between amide groups and carbonyl oxygens

Explain which types of interactions stabilize secondary structure

the combination of hydrogen bonding, hydrophobic interactions, and van der Waals forces work together to stabilize the secondary structure of proteins

Name four distinct types of secondary structure elements

1. α-helix

2. β-sheet

3. loops

4. turns

What type of bonds stabilize an α-helix? What are the functional groups that contain the atoms engaged in this interaction?

α-helix stabilized by H-bonds between backbone main chain carbonyl (C=O) and amide (N-H)

How far apart are the amino acids that are interacting (number of residues)?

the N-H group is 4 residues away from C=O

How many amino acid residues are in one turn of an α-helix?

3.6 amino acids per turn

What is the more frequent handedness (left or right-handed) of helical portions of proteins?

right-handed

alpha helices

- nearly all a-helices in proteins are right-handed

- ex: Ferritin, myoglobin, transmembrane sections

- stabilized by H-bonds (intrachain)

- R chains poke out

beta sheet

- zig-zag line

- several β-strands can be arranged in parallel to form a β-sheet

- H-bonds exist interstrand

anti-parallel beta sheets

- strands run in opposite direction

- more common + stable

parallel beta sheets

- strands run in same direction

- H-bonds at an angle (weaker)

- energetically unfavored

- can exist as β barrel, or twisted β sheet

loops and turns

turn of direction of polypeptide chain, link successive runs of α-helix or β-conformation

What is a superhelix? Name one example of a structural protein with a-helices forming a superhelix.

two or more alpha helices that intertwine

ex: keratin

How is the collagen helix different from an a-helix?. Be aware of the different terms "ahelix" (e.g. in keratin) and "a-chain" (in collagen).

- collagen is left-handed and has 3 residues per turn

- three of these helices (called α-chains) are wound around each other to form a coil

What is a b-sheet?

A region of peptides aligned next to each other to form a planar structure.

Which types of b-sheets are most stable?

anti-parallel