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Flashcards in Biochemistry week 1 Deck (127):
1

Distinguish between covalent chemical bonds and noncovalent forces

Covalent chemical bond: a chemical bond that involves the sharing of electron pairs between atoms. It can be polar OR nonpolar. (dependent on the difference on electronegativity scale, but if it is very large they become ionic bonding ie NaCl which is noncovalent) Noncovalent forces: They do not involve sharing a pair of electrons. Noncovalent bonds are used to bond large molecules such as proteins and nucleic acids. Noncovalent bonds are weaker than covalent bonds

2

Why do noncovalent bonds break and reform more readily than covalent bonds?

Noncovalent do not involve electron sharing and are much weaker and therefore can break and reform more easily

3

What is the distribution of water in the body and what is the avg volume?

Total volume: 40L Intracellular: 15L - Interstitial: 10L - Blood: 5L Extracellular: 25L - water is constantly moving between spaces in the body to maintain homeostasis

4

• List the four major types of noncovalent forces and explain their molecular basis

1.) Ionic interactions: formed between positive and negative ions. The bond is non-directional, meaning that the pull of the electrons does not favor one atom over another. An example is NaCl, which is formed between the positively charged Na+ ion and the negatively charged Cl- ion. The bond strength lessens when the distance between the two ions increases. (stabilizes protein structure) 2.) Dipole-Dipole & Hydrogen bonding: attraction of two permanent dipoles. Hydrogen bonding is an example and results when a hydrogen atom that is covalently bound to an electronegative atom (e.g. O, N, S) is shared with another electronegative atom. A hydrogen bond is directional toward the electronegative atom. An example of this is the hydrogen bonds formed in water. Hydrogen bonds are constantly being made and remade. (Permanent Dipole) 3.) London Dispersion forces: weak forces between temporary dipoles. These forces may be attractive or repulsive. They are also non-directional. Occurs in nonpolary molecules with orbiting electons producing a momentary dipole (induced dipole) 4.) Hydrophobic interactions: result when non-polar molecules are in a polar solvent, e.g. H2O. The non-polar molecules group together to exclude water (hydrophobic means water fearing). By doing so they minimize the surface area in contact with the polar solvent.

5

Describe what determines the polarity of a molecule, define permanent diplole and discriminate polar molecules from nonpolar compounds

Polarity: Polarity in organic chemistry refers to a separation of charge and can describe a bond or an entire molecule. Permanent dipole: Molecules which have an uneven distribution of charge (one end more positive than the other) are polar. Polar molecules are said to be permanent dipoles and have a permanent dipole moment () These molecules may or may not have a net charge of zero. Examples of polar molecules with a net charge of zero include water and carbon monoxide (See Table 2.1). Note that uneven distribution of charge alone does not make for a dipole moment. Carbon dioxide has its electrons pulled closer to the oxygens, but since the oxygens are on exactly opposite sides of each other, the dipole moments cancel each other out. Partial charges in a permanent dipole behave like fully ionic charges (opposites attract), but with less force. Permanent dipoles can be affected by ionic charges, by other permanent dipoles and by induced dipoles. Therefore nonpolar compounds do not have a significant dipole moment.

6

Describe the fundamental basis of hydrogen bonding, and recognize hydrogen bond donors and acceptors in biomolecules:

-electronegative atom (e.g. O, N, S) is shared with another electronegative atom.

7

Explain why CH3OH (methanol) molecules can form hydrogen bonds with water while CH4 (methane) molecules cannot:

methanol is polar because of the oxygen hogs the electron from the hydroxyl portion of the molecule, methane is not polar and electron sharing is evenly distrubuted

8

Explain how water molecules can act both as hydrogen bond donors as well as acceptors:

Water has a permanent dipole with the appearent negative charge at the oxygen (H acceptor) and a positive charge at the H atom (H donor)

9

• Describe what is induced dipole, explain its origin, and demonstrate how it contributes to van der Waals forces.

Induced dipole forces result when an ion or a dipole induces a dipole in an atom or a molecule with no dipole. These are weak forces.

10

What is the fundamental difference between van der Waals forces and electrostatic interactions?

van der Waals is a temporary dipole whereas electrostatic is a permanent dipole

11

Define amphipathic molecules and describe how an amphipathic molecule may interact with water

Contains both polar (water-soluble) and nonpolar (not water-soluble) portions in its structure Amphipathic molecules position their polar groups towards the surrounding aqueous medium whereas their hydrophobic chains towards the inside of the bilayer, defining a nonpolar region between two polar ones.

12

Explain how phospholipids in biological membranes remain happy in the aqueous environment of a cell?

Phospholipids group/bond together through london dispersion forces remain separated from the aqueous environment

13

What conditions cause excessive water loss and dehyddration of cells and what can it ultimately result in?

high blood glucose and diarrhea, which can lead to coma

14

What happens when NaCl dissolves in water?

Hydrogen bonds from water form shells around the ions

15

A Dehydrated Patient is Rehydrated With Intravenous Saline, what prevents large shifts of water or swelling during the adminstration of saline?

Intravenous saline, which is 0.9% NaCl solution called isotonic saline. Isotonic saline has an osmolality of approximately 290m Osm/kg H2O similar to the osmolality of the plasma, interstitial fluid and intracellular fluid

16

List major classes of molecules:

Proteins: Nucleic Acids: Carbohydrates: Lipids: Vitamins, Minerals:

17

Describe Carbon Hydrogen Structures: Aliphatic and Aromatic:

Aliphatic = non-aromatic Aromatic: planar, cyclic, conjugated (alternating) double bonds, special chemical stability due to cyclic delocalization of electron

18

describe a heterocyclic compound

Heterocyclic compound is an organic compound in which one or more of the carbon atoms in the backbone of the molecule has been replaced by an atom other than carbon. Typically: N, O, S

19

Draw/identify pyridine, pyrimidine and purine (heterocyclic compounds)

pyridine: benzene with one C replaced N pyrimidine: benezene with two C’s replaced N’s purine: (see pic)

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20

List DNA/RNA purine and pyrdimidines

Purines: adenine and guanine (Pure As Gold) Pyrimidines: cytosine, thymine (CUT) uracil for RNA

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21

Draw: Alcohol: Aldehyde: Ketone:

OH, R=O (terminal), ROR

22

Draw: Carboxylic acid Sulfhydryl group Disulfide

COOH, CSH, CSSC

23

Draw: Amino group (primary, quanternary)

CH2 - NH2, CH2 - N - (CH3)3

24

Draw: Ester Thioester Phosphoester Amide

COOR, COSR, POOR, CON

25

Draw: Phosphoric acid

H3PO4 ** phosphoric acid (inorganic phosphate) acts just like carboxcylic acid (same chemistry) **

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26

Ester is formed by:

acid + alcohol

27

Thioester formed by:

acid + sulfhydryl

28

Amide formed by:

acid + amine

29

Anhydride formed by:

acid + acid

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30

Most reduced form of carbon:

max amounts of C-H bonds thus CH4 is the most reduced

31

Most oxidized is when

Carbon is attached to X = O, N, S; thus CO2 is the most oxidized

32

Identify glycerol

3 C chain with 3 OH groups

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33

Describe the common features of biological membranes according to the Fluid Mosaic Model of Singer and Nicoloson

- The fluid mosaic model:.the plasma membrane around cells was made up from a phospholipid bilayer. This bilayer is made up from two layers of lipids, each with their hydrophobic tails facing inwards and their hydrophilic heads forming the surface. - The plasma membrane is a thin, permeable membrane which surrounds the cell. It controls any exchange in or out of the cell. - As well as lipids, the plasma membrane is made up of glycolipids, glycoproteins, transmembrane proteins and surface proteins. - The plasma membrane acts as a barrier against undesirable substances and cells but has many other uses too. The plasma membrane contains glycolipids and glycoproteins which allow it to be identified by other cells. - Many proteins are embedded in the bilayer

34

Exceptions to fluid mosaic model

Lipid bilayers are not smooth and even, partly because the protein surfaces are very rough and vary in size thus the lipid layers have to adjust to this and it is very fluid.

35

Categorize the types of proteins associated with membranes and correlate the different types of interaction with protein structure

PERIPHERAL MEMBRANE PROTEINS Are hydrophilic only. Bind to either the inner or outer membrane via noncovalent interactions with other membrane proteins. Do not extend into the hydrophobic interior of the membrane.

TRANSMEMBRANE PROTEINS

Are amphipathic (have both hydrophobic and hydrophilic regions). Hydrophobic regions pass through the hydrophobic interior of the membrane and interact with the hydrophobic tails of the lipid molecules. Hydrophilic regions are exposed to water on both sides of the membrane. Membrane proteins play many important roles in the plasma membrane, including functioning in transport and as receptors and enzymes.

TRANSPORT PROTEINS

Transmembrane proteins that allow small polar molecules (that would otherwise be inhibited by the hydrophobic interior of the plasma membrane) to cross the lipid bilayer. There are two main classes of transport proteins

Carrier proteins (transporters): Undergo conformational changes to move specific molecules across the membrane. Channel proteins (ion channels): Form a narrow hydrophilic pore to allow passage of small inorganic ions.

 

36

Define and discuss lipid polymorphism

Polymorphism in biophysics is the aspect of the behaviour of lipids that influences their long-range order, i.e. how they aggregate. This can be in the form of spheres of lipid molecules (micelles), pairs of layers that face one another (lamellar phase, observed in biological system as a lipid bilayer), a tubular arrangement (hexagonal), or various cubic phases. Lipsomes are thermodynamically favored because the structure no longer has a hydrophobic edge

37

Discuss the factors that control membrane fluidity

Factors that affect the fluidity of the membrane:

Temperature, cholesterol content, and phospholipid type, chain length type (increases melting point Tm), double bonds decrease Tm, head groups

The fluidity of the cell membrane:

- ↑ temperature increases fluidity
- The longer the tail, the less fluid the membrane (increased london dispersion force)
- Unsaturated fatty acids increases fluidity because it can't pack tightly
- Cholesterol levels prevent movement and decrease fluidity Note that cholesterol makes membranes less fluid while at the same time less subject to phase transitions.

**  Marks has a question which states that cholesterol increases disorder and wikipedia states "Cholesterol acts as a bidirectional regulator of membrane fluidity because at high temperatures, it stabilizes the membrane and raises its melting point, whereas at low temperatures it intercalates between the phospholipids and prevents them from clustering together and stiffening."**

 

38

Describe phosopholipid mobility:

flexion (wiggle), rotation (inplace), lateral diffusion (switch with neighbor), XX flip flop rarely occurs (switching from inside to outside of bilayer

39

Define and describe membrane fusion

Membrane Fusion: The process by which two initially distinct lipid bilayers merge their hydrophobiccores, resulting in one interconnected structure. If this fusion proceeds completely through both leaflets of both bilayers, an aqueous bridge is formed and the internal contents of the two structures can mix. Alternatively, if only one leaflet from each bilayer is involved in the fusion process, the bilayers are said to be hemifused. In hemifusion, the lipid constituents of the outer leaflet of the two bilayers can mix, but the inner leaflets remain distinct. The aqueous contents enclosed by each bilayer also remain separated.

40

Briefly discuss the roles that membrane lipids may have in addition to forming lipid bilayers; provide one example

Membrane lipids serve as regulatory agents in cell growth and adhesion, participate in biosynthesis of other biomolecules, and can increase enzymatic activities of enzymes

41

• Define acids and bases in reference to the H+ and OH-

Acids: compounds that donate a hydrogen ion (H+) to a solution Bases: compounds (such as OH-) that accept hydrogen ions

42

How is the acidity of a solution related to its H+ concentration, and how is the basicity of a solution related to its OH- concentration?

Increased concentration of H+ means more acidic and that the protons are looking for electrons and are free floating in an unhappy/less stable form (OH- looking for protons to be stabilized)

43

Distinguish between a strong acid and a weak acid-base conjugate

Strong acids: are completely dissociated. Low pKa values (H+ binds loosely to the conjugate base) Weaker acids: are less completely dissociated. High pKa values. (H+ binds tightly to the conjugate base)

44

Why is HCl considered to be a stronger acid than acetic acid?

A strong acid is one which is virtually 100% ionised in solution. Hydrogen chloride dissolved in the water splitting to give hydrogen ions in solution and chloride ions in solution. It basically means that the H and Cl are easily split. A weak acid is one which doesn't ionise fully when it is dissolved in water and in the case of acetic acid has resonance forms that stabilize it, making it more difficult to ionize because it is happy.

45

• Define pH, and show its relationship with hydrogen ion concentration

pH is a measure of acidity of a solution, acid < 7, base >7 pH = -log [H+]

46

Calculate the change in hydrogen ion concentration when the pH of a solution is raised from 6.5 to 7.5.

pH 6.5 => [H+] = 3.1 x10-7 pH 7.5 => [H+]= 3.1 x10-8 **Note the hydrogen ion concentration decreased as pH was raised difference is x10^1**

47

• Explain what pKa is, and show its relationship to Ka

pKa: when acidic dissociation is at equilibrium, the acidic dissociation constant Ka is defined by: Ka = [H+] [A-]/ HA pKa: is the measure of the strength of an acid Stronger acids are more completely dissociated and have low pKa values pKa = -Log10(Ka)

48

• Use the Hendersen-Hasselbalch equation to explain the relationship between pH and pKa.

**pH = pKa + log [A-] / [HA] ** [A-] = molar concentration of a conjugate base (proton acceptor) [HA] = molar concentration of a undissociated weak acid (M) (proton donor)

49

If the pKa of a dissociable group is 6.5, what percentage of the compound is in the dissociated form at pH 7.0?

pKa = 5

50

• Describe what is meant by the ion product of water

The Ionic Product of Water, Kw, is the equilibrium constant for the reaction in which water undergoes an acid-base reaction with itself. That is, water is behaving simultaneously as both an acid and a base. H2O(l) + H2O(l) = H3O+(aq) + OH-(aq) Kw = [H3O+(aq)][OH-(aq)]

51

What is the concentration of H+ in a solution of 0.01 M KOH?

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52

• Explain what a buffer is, and why weak acids and bases are better biological buffers than strong acids and bases

A buffer is a solution that contains a mixture of a weak acid and its conjugate base. It resists changes in [H+] on addition of acid or alkali. A weak acid has a flat zone which is the buffering region ie example on graph (3.76 to 5.76) The midpoint of this region is the pKa. (example would be 4.76 for last set of numbers)

53

Explain why lactic acid can act as a buffer while HCl cannot.

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54

• Describe the concept of titration, interpret a titration curve, and identify compounds with dissociable groups from their respective titration curves

Titration is the slow addition of one solution of a known concentration (called a titrant) to a known volume of another solution of unknown concentration until the reaction reaches neutralization. In a broad sense, titration is a technique to determine the concentration of an unknown solution.

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55

From the figure below identify the titration curve for HCl and for CH3COOH, and justify your answer.

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“A” has a rapid rise represents a strong acid = HCl, “B” is CH3COOH and is a weak acid and has a defined buffer zone.

56

• Explain the significance of the pKa of a buffer with respect to buffering capacity

Buffer capacity is a measure of the efficiency of a buffer in resisting changes in pH. Conventionally, the buffer capacity () is expressed as the amount of strong acid or base, in gram-equivalents, that must be added to 1 liter of the solution to change its pH by one unit. Calculate the buffer capacity as: = gram equivalent of strong acid/base to change pH of 1 liter of buffer solution = the pH change caused by the addition of strong acid/base In practice, smaller pH changes are measured and the buffer capacity is quantitatively expressed as the ratio of acid or base added to the change in pH produced (e.g., mEq./pH for x volume). The buffer capacity depends essentially on 2 factors: Ratio of the salt to the acid or base. The buffer capacity is optimal when the ratio is 1:1; that is, when pH = pKa Total buffer concentration. For example, it will take more acid or base to deplete a 0.5 M buffer than a 0.05 M buffer.

57

If you need to maintain a pH of 6.5 in an experiment and the only available buffers are the ones below, which one should you use and why? Buffer A with a pKa of 6.8 Buffer B with a pKa of 7.6 Buffer C with a pKa of 5.2

Buffer A because the pKa of a buffer is the midpoint and it is the closest to the required pH

58

• List biological compounds known to have significant buffering capacity inside our body

1) protein buffering system: Hemoglobin is the most important buffer in the protein buffer system. It works because the of the aminio acid side chains are ionizable. 2) phosphate buffering system: Acts in the cytoplasm of the cells 3)Bicarbonate buffering system:

59

• Describe how the bicarbonate buffer system works to maintain a constant pH in our blood and tissues

Carbonic acid (H2CO3) is a weak acid and is therefore in equilibrium with bicarbonate (HCO3-) in solution. When significant amounts of both carbonic acid and bicarbonate are present, a buffer is formed. This buffer system can be written as: H2CO3 + H2O H3O+ + HCO3- Under normal circumstances there is much more bicarbonate present than carbonic acid (the ratio is approximately 20:1). As normal metabolism produces more acids than bases, this is consistent with the body's needs. The blood, with its high base concentration, is able to neutralize the metabolic acids produced. Since relatively small amounts of metabolic bases are produced, the carbonic acid concentration in the blood can be lower. Since carbonic acid is not stable in aqueous solutions some of it decomposes to form carbon dioxide and water. The respiratory system is responsible for removing the carbon dioxide. H2CO3 H2O + CO2 By combining the two reactions of carbonic acid we can write: 2 H2O + CO2 H2CO3 + H2O H3O+ + HCO3- It is the production of carbon dioxide from this reaction that couples the carbonic acid/bicarbonate buffer to the respiratory system. Metabolic waste products are transferred from muscles and organs into the blood. As there are a number of acids produced, this would have the effect of lowering the blood pH. The buffer system counteracts this effect. Consider the production of lactic acid in muscles. Lactic acid is a weak acid and, when it enters the blood, donates a proton to water to produce H3O+. This increases the H3O+ concentration. In order to restore the H3O+ concentration to normal, the equilibrium below shifts to the left. H2CO3 + H2O H3O+ + HCO3- This shift results in the production of H2CO3. In order to reduce the H2CO3 concentration, the equilibrium below shifts to the left as well. 2 H2O + CO2 H2CO3 This shift results in the production of CO2. In the lungs, the CO2 leaves the blood, is exhaled and normal blood pH is maintained.

60

What is the significance of CO2 in the bicarbonate buffer system?

It is the byproduct of the carbonate acid becoming water and CO2 which can be removed by the lungs

61

• Distinguish between a closed and an open buffer system and evaluate the importance of our blood buffering system in the context of that concept.

Open => things can leave the solution The ability of CO2 to be released out of solution in the lung, means it is an open system. Otherwise, it would be a closed system

62

Identify the following aromatic amino acids: Phe: Tyr: Trp:

Phe: Phenylalanine Tyr: Tyrosine Trp: Tryptophan

63

Identify the following nonpolary aliphatic amino acids by their three letter code: Gly: Ala: Val: Leu: Ile: Met: Pro:

Gly: Glycine Ala: Alanine Val: Valine Leu: Leucine Ile: Isoleucine Met: Methionine Pro: Proline

64

Identify the following polar uncharged amino acids: Asn: Gln: Ser: Thr: Cys:

Asn: Asparagine Gln: Glutamine Ser: Serine Thr: Threonine Cys: Cysteine

65

• Draw the general structural plan of amino acid molecules and identify the α-carbon, the carboxylic carbon, the amino nitrogen and the position of the side chain

reference pic

66

Which one of the two carbon atoms in an amino acid molecule takes part in peptide bond formation- the α-carbon or the carboxyl carbon?

carboxyl

67

Which are Acidic Aminos?

Aspartic Acid & Glutamic acid contain an additional carboxylic acid group and are (-) charged at pH 7.4; polar

68

Which are the basic amino acids

(polar and very hydrophilic, first two (+) at phys pH) Lysine, Arginine (most basic), Histidine (no charge at phys pH)

69

10 Essential amino acids (obtained through diet)

PVT TIM HALL Phyenylalanine (phe) Valine (val) Threonine (thr) Trytophan (trp) Isoleucine (Ile) Methionine (Met) Histidine (his) Arginine (arg) Leucine (leu) Lysine (lys)

70

Nonessential amino acids:

(TCA cycle and other metabolic intermediates) Tyrosine (Tyr) Glycine (Gly) Alanine (Ala) Cysteine (cys) Serine (ser) Aspartate (asp) Asparagine (asn) Glutamate (glu) Glutamine (gln) Proline (pro)

71

What is unique about proline?

Proline: provides more rigidity to a structure because the side chain is connected to the amino group

72

What is special about glycine?

Most simple aminio is glycine and it makes the chain flexible, takes up small amount of space

73

Aromatic amino acids? Unique characteristics?

Aromatic side chains relatively nonpolar. Participate in hydrophobic interactions. Phenylalanine is able to pie pie stacking which stabilized the protein Tyrosine: is important for phosphorylation and uncogensis Tryptophan and tyrosine can hydrogen bond and spike at 218 wavelength in UV spectomotry

74

Which amino acid can disulfide bond / describe disfulide bonds:

Cysteine: Disulfide linkages are covalent bonds (involve electron sharing) and play a critical role in protein architecture. Once formed the disulfide linkages prefer a hydrophobic environment. Sulfhydryl group is hyrophilic and polar (can occur spontaneously)

75

What’s an example of where we see disulfide linkages in the body?

Insulin has three disulfide linkages and holds the molecule together (important fucntion)

76

• Recognize the sulfur-containing amino acid side chains, and explain formation of disulfide bond between two cysteine residues

The third group shows the two amino acids with sulfur atoms in their side chains: cysteine and methionine. The amino acid cysteine can, under appropriate conditions, bond to a second molecule of cysteine through its side chain. The resulting bond is between the sulfur atoms of the two cysteine molecules and is called a disulfide bridge. The new molecule that forms is called cystine. This ability of cysteine to form disulfide bridges will turn out to be important in maintaining the structure of some proteins. Note that this reaction involves the removal of two hydrogen atoms along with their electrons. It is therefore an oxidation reaction. The reaction can be reversed by replacing the two hydrogen atoms and splitting apart the two sulfur atoms. The reverse of this reaction is, of course, a reduction reaction.

77

• List the amino acid side chains with dissociable groups, and identify their ionized and deionized states

Tyrosine (tyr), cysteine (cys), aspartate (asp), glutamate (glu), histidine (his), arginine (arg), lysine (lys)

78

List examples of Human Disease linked to single amino acid changes:

Sickle cell anemia: mutation subsitituting glutamate residue with a valine at position 6 of the b-subunit of hemoglobin causes the mutated protein to aggregate with each other. Leads to deformation and premature destruction of RBC causing sickle cell anemia Osteogenesis imperfecta (type II): mutation substituting glycine residues with Aspartate at 547, 580, 805, 907 or 976 of the COL1A1 gene product cause collagen deformation resulting in perinatal lethality Testicular feminization: substitution of single cysteine residue at positions 557 or 574 with a tryptophan or arginine in androgen receptor protein leads to a physiological abnormality. Males carrying this mutation develop femal secondary sexual characteristics.

79

Describe a few protein roles? What determines protein structure and function?

* Proteins roles: (e.g., as enzymes, hormones, receptors, antibodies, structural components, transporters of other compounds, and contractile elements in muscle). * linear sequence of amino acid residues in a polypeptide chain determines the three- dimensional configuration of a protein, * the structure of a protein determines its function.

80

Describe primary protein structure:

Primary structure of a protein consists of the amino acid sequence along the chain. - Charges on polypeptide chain are due only to the N-terminal amino group, C terminal carboxyl group and side chains on amino acid residues

81

Describe secondary protein structure:

Secondary structure involves α-helices, β-sheets, and other types of folding patterns that occur due to a regular repeating pattern of hydrogen bond formation. - local conformations which side chains are not involved - α-helix: carbonly of a peptide bond forms a hydrongen bond with NH of a peptide bond four amino acid residues away. Side chains face outward. Proline disrupts an α-helix - β-sheets: formed by hydrogen bonds between two extended polypeptide chains or between two regions of a single chain that folds back on itself. Interactions between carbonyl of one peptide bond and the NH of another - Supersecondary structures: certain folding patterns involving α-helices and β-sheets including the helix-turn-helix, leucine zipper, zinc finger

82

Describe tertiary protein structure:

Tertiary structure (the three-dimensional conformation of a protein) involves electrostatic and hydrophobic interactions, van der Waals interactions, and hydrogen bonds and disulfide bonds. Involves interactions between amino acid residues that can be a considerable distance apart. - Hydrophobic aminio acids residues tend to collect in the interior of globular proteins to exclude water, hydrophilic residues found at the surface - Noncovalent bonds that provide structure: hydrophobic interactions, van der Waals interactions, and hydrogen bonds - Covalent bonds that provide structure: disulfide bonds

83

Describe quatenary protein structure:

Quaternary structure refers to the interaction of one or more subunits to form a functional protein, using the same forces that stabilize the tertiary structure. - joined together by the same types of interactions as tertiary structures

84

Why does a peptide unit considered to be planar? What contributes to the planar nature of a peptide unit?

There is a resonance structure between the carbonyl structure and N in the peptide link

85

What contributes to the flexibility of a polypeptide chain? How is that flexibility balanced so that a three-dimensional structure can be achieved?

Freedom of rotation on either side of the alpha carbon allows folding in many different ways, but it is balanced with the planar peptide bonds (secondary to resonance forms) which add rigidity and enable well defined 3-D structures, also streric hindrance limits rotation

86

At what level of protein structure does hydrogen bonding become a key determinant, primary, secondary, tertiary or quaternary?

secondary (1,4 bonding on helix via h bonding/2,6) for helix

87

Describe the structural features of the two major periodic structures of proteins: alpha helix and beta sheet. Differentiate between them with special emphasis on the nature of hydrogen bonding

- α-helix: carbonly of a peptide bond forms a hydrongen bond with NH of a peptide bond four amino acid residues away. Hydrogen bonding creates a repetitive pattern. Side chains face outward. Proline disrupts an α-helix - β-sheets: formed by hydrogen bonds between two extended polypeptide chains or between two regions of a single chain that folds back on itself. Interactions between carbonyl of one peptide bond and the NH of another. A beta sheet is non-repetitive

88

Is it feasible for an amino acid residue at position 6 of a polypeptide chain to remain hydrogen bonded to a residue at position 20 and still be part of a single -helix, or a single -sheet? In both cases, justify your answer.

For alpha helix it is not possible (hydrogen bond every four to maintain the tight structure. For a beta sheet it is possible because the chain can fold back on itself

89

Differentiate between parallel and antiparallel -sheets

parallel sheets: N terminal and C terminal of each strand are on the same end antiparallel sheet: N terminal and C from different strands are lined up

90

Say there are two sheets each containing four strands of similar length, but one is arranged in a parallel and the other in an antiparallel orientation. Of the two conformations which one will require a longer polypeptide chain to construct?

parallel arranged

91

Explain the significance of loop regions and turns in protein structure and function

Loop regions are often found to constitute enzyme active sites and are rich in polar and charged residues. They also mediate interaction with other molecules and allow flexibility to form antigen binding sites. Turns play a critical role in folding by bringing together and enabling or allowing interactions between regular secondary structure elements.

92

Describe why proline is not a good helix former:

proline has steric hindrance and reduces flexibility in a chain

93

Describe the molecular basis of prion protein aggregation

Protein PrPc form changes from a helical structure to a beta sheet, where beta sheet favors aggregation (intersheet hydrogen bonding) vs alpha helix has no spare molecules for hydrogen bonding. Seen prion diseases such as mad cow and Creutzfeldt-Jakob disease

94

In an alpha helix how many aminos/molecules are there per turn for the h-bond?

3.6/13

95

Describe a post-translation modification:

Posttranslational modifications of proteins occur after the protein has been synthesized on the ribosome. Phosphorylation, glycosylation, ADP ribosylation, methylation, hydroxylation, and acetylation affect the charge and the interactions between amino acid residues, altering the three-dimensional configuration and, thus, the function of the protein.

96

• Define supersecondary structures or motifs, and explain their functional significance

A compact three-dimensional protein structure of several adjacent elements of secondary structure that is smaller than a protein domain or a subunit and have specific geometric arrangements. Supersecondary structures can act as nucleations in the process of protein folding and have specific functional roles (between secondary and tertiary structure) Motifs are relatively small arrangements of secondary structure that are recognized in many different proteins; for example, certain of the beta-strands are connected with alpha-helices to form the structural motif.

97

What biological function is associated with the helix–loop-helix structure?

calcium binding, DNA binding

98

Is helix-loop-helix considered a motif or a domain? Justify your answer.

motif (Protein domains are a structural entity, usually meaning a part of the protein structure which folds and functions independently.)

99

Describe domains with special reference to globin fold. Explain how domains are associated with a specific functions and contribute to the architecture of multifunctional proteins

(Need more info on this) Globin Fold: Built Exclusively from a-helices and loops. Designed to bind oxygen through a heme group. Present in Myoglobin and Hemoglobin The tertiary structure of myoglobin consists of eight -helices connected by short coils, a structure that is known as the globin fold

100

• Summarize the types of modified amino acid residues found in protein, their functional significance, the respective chemical group associated with the modifications, and the amino acid residues modified in each case

*** Glycosylation*** The reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule Group attached: carbohydrate, i.e. a glycosyl donor, Site of modification: NH2 of asparagine, OH of serine and threonine Functional significance: protein targeting (membrane proteins and secretory proteins) protein folding • Lipid attachment Group attached: lipid Site of modification: cysteine, glycine Functional significance: allows membrane anchoring of proteins *** Phosphorylation *** Group attached: phosphate Site of modification: serine, threonine and tyrosine (conformational changes) Functional significance: regulation of protein activity especially enzymes (turns them on and off) • Acetylation Group attached: acetyl Site of modification: lysine; -NH2 terminal Functional significance: resistance to degradation, alters DNA binding properties of histone • Carboxylation Group attached: carboxylic acid Site of modification: glutamate Functional significance: Ca2+ binding • Hydroxylation Group attached: hydroxl Site of modification: proline Functional significance: maturation and secretion of collagen

101

Which amino acid is structurally closest to selenocysteine? Which amino acid is selenocysteine derived from?

** Selenocysteine is derived from serine (resembles cysteine) found in some enzymes for catalytic activity

102

What is the functional significance of protein farnesylation?

some cancers are farnesylated so a drug that inhibits farnesyl transferases may be a potential cancer tx

103

State the basic difference between an N-linked and an O-linked glycosylation of protein.

NH2 of asparagine, OH of serine and threonine

104

Reversible attachment of phosphate groups to protein molecules has either a regulatory or signaling function. Which amino acid residues are best known as the potential sites for protein phosphorylation?

serine, threonine and tyrosine

105

• How posttranslational modification play a critical role in collagen structure

Interhelical Hydrogen Bonding Requires Hydorxylation of Proline and allows a tightly packed triple helix

106

How does hydroxylation of the Pro residues in a collagen helix reinforce the triple-helix structure? What is the significance of having a Gly residue at every third position of a collagen helix?

Pro hydrogen bonds with the backbone and interhelical bonding. Gly is the only amino residue that fits and allows it to be tight because it has such a short side chain. The problem with osteogenisis imperfecta the glycine is replaced with aspartate (which is larger and negative, which repels)

107

• List the metal ions that are commonly found to be part of protein tertiary structure enhancing functional capability, with special reference to globin fold and zinc finger structures: Globin fold:

iron, designed to bind oxygen through a heme grou (myoglobin and hemoglobin) Zinc finger structure: binds to DNA through cysteines and/or histidines0

108

State the fundamental difference between the mechanisms by which a globin fold coordinates a Fe2+ atom and a zinc finger motif coordinates a zinc atom.

?

109

Identify the amino acid residues that are good metal ligands:

Those that have ionizable side chains: glu, asp, cys, his

110

Describe the architectural plan of the coiled-coil structure of a leucine zipper, and its function

Usually found as part of a DNA-binding domain in various transcription factors, and are therefore involved in regulating gene expression. Has a heptad repeat creates the coiled coil

111

• Demonstrate how the information for protein folding is encoded within the primary structure of a protein (ribonuclease A)

In the case of ribonuclease A sulfhydrase is spaced out in intervals that allow it create disulfide bonds when it folds and it is therefore stabilized.

112

• Describe how different physical and chemical factors may affect protein stability, and define protein denaturation and protein stability

Protein stability is provided by: - Noncovalent bonds that provide structure: hydrophobic interactions, van der Waals interactions, and hydrogen bonds - Covalent bonds that provide structure: disulfide bonds Protein denaturation: a. Proteins can be denatured by agents such as heat and urea that cause unfolding of polypeptide chains without causing hydrolysis of peptide bonds. b. The denaturing agents destroy secondary and tertiary structures, without affecting the primary structure. c. If a denatured protein returns to its native state after the denaturing agent is removed, the process is called renaturation.

113

• Define conformational change of proteins and distinguish it from the process of protein denaturation

Protein conformational change: A macromolecule is usually flexible and dynamic. It can change its shape in response to changes in its environment or other factors; each possible shape is called a conformation, and a transition between them is called a conformational change. The denaturing agents destroy secondary and tertiary structures, without affecting the primary structure.

114

What is the fundamental difference between protein denaturation and protein conformational change?

Conformational change is always reversible/temporary state vs denaturation can be permanent and it a destructive process occurring

115

• Define Isoelectric point (pI), and describe its significance in diagnostic proteomics

The characteristic pH at which the net electric charge of the molecule is zero. Allows analysis of normal cells and diseased cells (cancer cells) from the same tissue, which will hopefully help with molecularly fingerprinting tumors and novel targets for drugs with tailored Tx.

116

• Explain why enzymes are called biological catalysts

Physiological conditions are very mild for chemical reactions and provide the neccessary environment for chemical reactions at a faster rate (catalyst = remains unchanged and is reused)

117

• Distinguish between an uncatalyzed and a catalyzed reaction mechanistically

start (substrate) and finish (product) will be the same, but catalyzed reaction is faster with different intermediate complexes

118

• Describe the structural and functional significance of an enzyme active site

Enzyme active site has restricted access

119

• Define the terms EP and ES in an enzyme catalyzed reaction

Enzyme-Product Complex Enzyme-Substrate Complex

120

• Distinguish between substrate binding and substrate catalysis, and describe how both functions can be accomplished by the active site

binding causes a conformational change, catalysis lower the activation energy of the reaction

121

• Define cofactors and coenzymes; describe their roles in the active site of an enzyme

Coenzyme and cofactor: help with binding of substrate and/or catalysis

122

• Identify the active groups of the activation-transfer coenzymes (such as thiamine pyrophosphate, pyridoxal phosphate, coenzyme A, biotin) and oxidation-reduction coenzymes such as NAD+

"Thiamine pyrophosphate: a reactive carbon atom with a dissociable proton in a thiazolium ring Group Transferred: Thiamine pyrophosphate Pyridoxal phosphate: reactive aldehyde group which transfers amino group by forming a covalent bond Group Transferred: Amino group Coenzyme A: nucleophile that attacks carbonyl groups, reactive thiol group Group Transferred: Acyl group NAD+: catalyzes conversion of lactate to pyruvate, carbon atom in nicotinamide ring Group Transferred: Hydride ion"

123

• Summarize the different roles that metal ions can play in enzyme catalyzed reactions

metal ions can help facilitate the release of a proton

124

• List the six major classes of enzymatic reactions and identify the types of chemical reactions catalyzed by each of them

Oxioreductase: Oxidation reduction reaction (catalyzes the transfer of electrons from one molecule, the reductant) Transferases: Group Transfers (transfer of specific functional groups) Hydrolases: Hydrolysis (cleavage of chemical bonds by the addition of water) Lyases: Removal of elements of H2O or CO2 ( (an "elimination" reaction) of various chemical bonds by means other than hydrolysis (a "substitution" reaction) and oxidation, often forming a new double bond or a new ring structure) Isomerase: Isomerization (one molecule is transformed into another molecule which has exactly the same atoms, but the atoms have a different arrangement) Ligases: Ligation (requires energy) (the covalent linking of two ends of DNA or RNA molecules)

125

What are the four major phosopholipids in the membrane?

Innermembrane: phosphatidylethanolamine, phosphatidylserine
Outermembrane: sphingomyelin and phosphatidylcholine

126

What are the three classes of membrane lipids?

phospholipids, holesterol, glycolipids

127

How do drugs like oubain and cardiac glycosides (digoxin and digitoxin)  increase cardiac contractility?

both bind and inhibit the Na+-K+ ATPase by competing for sites with on the extracellular side of the pump. The binding of these inhibitors results in increased cardiac contractility (through a Ca2+- dependent mechanism).

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