Exam 1 Flashcards

1
Q

(COVALENT/NONCOVALENT) bonds are strong, short, and share electrons.

A

Covalent

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2
Q

(COVALENT/NONCOVALENT) bonds are weak, long, and are by attraction only.

A

Noncovalent (interactions)

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3
Q

Covalent bonds that hold monosaccharides (carbohydrates) together to create polysaccharides are…

A

Glycosidic bonds

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4
Q

Covalent bonds that hold fatty acids plus glycerol or sphingosine derivatives together to from phospholipids or triacylglycerol are called…

A

Ester bonds

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5
Q

Covalent bonds that hold amino acids together to form polypeptides are called…

A

Peptide bonds

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6
Q

Covalent bonds that hold nucleotides together to form oligonucleotides or polynucleotides are called…

A

Phosphodiester bonds

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7
Q

The strength of a covalent or non covalent bond is measured by the _______ needed to break the bond.

A

Energy

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8
Q

Put the following bonds in order from weak to strong–

A. Salt bridges; Hydrogen bonds
B. Covalent bonds
C. Van der Waals interactions

A
  1. C
  2. A
  3. B
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9
Q

The strength of a bond can depend on the ________ between atoms.

A

Distance

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10
Q

How do we measure how attractive 2 ions are to each other in a vacuum?

A

Use Coulomb’s Law – F = k q1q2
——-
r(squared)

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11
Q

In Coulomb’s Law, F = Force between ions in Newtons. If F > 0 that means the ions are (ATTRACTIVE/REPULSIVE), and if F < 0 that means the ions are (ATTRACTIVE/REPULSIVE).

A

Repulsive

Attractive

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12
Q

If we want to measure how attractive the 2 ions are to each other in a biological environment, what do we need to add to Coulomb’s Law?

A

Relative permittivity

***Add D (dielectric constant) to the denominator (in air = 1)

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13
Q

What is the energy required to separate two ions?

A

Energy of interaction

**If E < 0 then there is an attraction

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14
Q

A dipole means having a ______ charge.

A

Partial

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15
Q

Dipoles can be _______ (polar) or _______ (polarizable).

A

Permanent

Induced

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16
Q

With this type of bond, an electron pair is shared.

A

Covalent bonds

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17
Q

What is the average distance of a covalent bond?

A

1 angstrom

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18
Q

What types of bonds interact through charge attraction?

A

Charge and/or dipole interactions

van der Waals interactions

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19
Q

What is the average distance of the charge and/or dipole interactions?

A

3 angstroms

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20
Q

What is the average distance of the van der Waals interactions?

A

3-4 angstroms

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21
Q

What type of bond shares a hydrogen atom/proton?

A

Hydrogen bonds

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22
Q

What is the average distance of hydrogen bonds?

A

2.6-3.7 angstroms (between donor and acceptor)

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23
Q

Water’s strange physical properties are explained by its _______ bonding ability.

A

Hydrogen

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24
Q

Ice (solid) is less dense than liquid water, and the hydrogen bond distances are (GREATER/SMALLER) in the solid than in the liquid.

A

Greater

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25
Q

This is a measure of how highly packed atoms or molecules are.

A

Density

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26
Q

This is the amount of heat needed to change the temperature of 1 g of a given substance by plus or minus 1 degree Celsius.

A

Specific heat capacity

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27
Q

This is the amount of energy needed to change 1 g of a given substance from liquid to gas.

A

Heat of vaporization

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28
Q

Hydrogen bonds _____ energy to break and ______ energy when they form.

A

Take

Release

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29
Q

The surface of water is strong. _______ is when water molecules attract each other (attraction to self). _______ is when water and other polar substances attract each other (attraction to other).

A

Cohesion

Adhesion

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30
Q

Cohesion creates what?

A

Surface tension

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31
Q

Cohesion and adhesion work together to create ______ ______.

A

Capillary action

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32
Q

Water is the _______ solvent.

A

Universal

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33
Q

Charged/Polar molecules are (HYDROPHOBIC/HYDROPHILIC) and (DISSOLVE/SEPARATE).

A

Hydrophilic

Dissolve

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34
Q

Nonpolar molecules are (HYDROPHOBIC/HYDROPHILIC) and (DISSOLVE/SEPARATE).

A

Hydrophobic

Separate

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35
Q

_______ molecules have both hydrophilic and hydrophobic parts.

A

Amphipathic

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36
Q

Chemical _______ is making and/or breaking chemical bonds.

A

Reactions

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37
Q

Most reactions are ________.

A

Reversible

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38
Q

Equilibrium (DOES NOT/DOES) mean there are equal concentrations. There is no net formation or destruction.

A

Does not

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39
Q

A weak acid is a proton (ACCEPTOR/DONOR).

A

Donor

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40
Q

A conjugate base is a proton (ACCEPTOR/DONOR).

A

Acceptor

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41
Q

What is the dissociation constant?

A

Ka (or Kb)

**Means acid is “falling apart”

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42
Q

What is the dissociation constant equation (Ka)?

A

Ka = [H+] [A-]
————
[HA]

**Products over reactants

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43
Q

Strong acids are always going to fall apart completely, so that means its Ka value will be (LARGER/SMALLER) and its pKa value will be (LARGER/SMALLER).

A

Larger

Smaller

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44
Q

Little “p” means _____, so that means Ka and pKa will always be opposites (i.e., big/small).

A

-log

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45
Q

Weak acids kind of fall apart, so that means its Ka value will be (LARGER/SMALLER) and its pKa value will be (LARGER/SMALLER).

A

Smaller

Larger

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46
Q

If it’s a strong acid it will be easier to break apart, therefore requiring less energy. This means the energy required will be (MORE/LESS) negative.

A

Less

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47
Q

If it’s a weak acid it will be more difficult to break apart, therefore requiring more energy. This means the energy required will be (MORE/LESS) negative.

A

More

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48
Q

A weak base is a proton (ACCEPTOR/DONOR).

A

Acceptor

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49
Q

A conjugate acid is a proton (ACCEPTOR/DONOR).

A

Donor

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50
Q

What is the equation for pKa?

A

pKa = -log Ka

** (or) pKb = -log Kb

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51
Q

What is the equation for the dissociation constant Kb?

***Remember for a BASE, the base itself is not dissociating, it is the WATER that is dissociating.

A

Kb = [BH+] [OH-]
—————–
[B]

***Products over reactants

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52
Q

A strong base requires more energy because it’s moving to an acid, therefore the required energy amount is (MORE/LESS) negative.

A

More

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53
Q

A weak base requires less energy moving to an acid, therefore the required energy amount is (MORE/LESS) negative.

A

Less

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54
Q

pKw = -log Kw = ????

A

14

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55
Q

pKw = pH + ????

A

pOH

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56
Q

pH = -log [???]

A

H+

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57
Q

What is the equation for Kw?

A

Kw = [H+] [OH-] = 10(-14) M
—————
[H2O]

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58
Q

What is physiological pH?

A

7.4

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59
Q

This is the term for a weak acid or weak base that can stabilize pH (absorb protons).

A

Buffer

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60
Q

What is the Henderson-Hasselbach equation?

A

pH = pKa + log ( [A-] )
——-
( [HA] )

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61
Q

What is the alternate equation we are going to use for Henderson-Hasselbach?

A

[A-]
—– = 10(pH-pKa)
[HA]

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62
Q

If pH < pKa, then our exponent is going to be negative (in modified HH equation). This means our overall value is between 0 and 1 and that most of the molecules are _______ since [HA] > [A-].

A

Protonated

Acid concentration is higher, that means there are more protons present (hence PROTONATED)

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63
Q

If pH > pKa, then our exponent is going to be positive (in modified HH equation). This means our overall value is greater than 1 and that most of the molecules are _______ since [HA] < [A-].

A

Deprotonated

Base concentration is higher, that means there are less protons present (hence DEPROTONATED)

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64
Q

If pH = pKa, then our exponent is going to be 0 (in modified HH equation). This means our overall value is 1 and that the molecules are just as likely to be _______ or _______ since [HA] = [A-].

A

Protonated

Deprotonated

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65
Q

In gel _________, the direction of migration is based on the net charge of the molecule (negative goes toward positive).

A

Electrophoresis

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66
Q

This is when the pH of ALL molecules of a given species in solution have an overall charge of 0.

A

Isoelectric Point (pI)

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67
Q

If pH < pI, that means the pH < pKa so the molecule is protonated. Thus, the molecule must have a (NEGATIVE/POSITIVE) charge.

A

Positive

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68
Q

If pH > pI, that means the pH > pKa so the molecule is deprotonated. Thus, the molecule must have a (NEGATIVE/POSITIVE) charge.

A

Negative

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69
Q

If pH = pI, then (by definition) the molecule no net ______.

A

Charge

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70
Q

The pI equations is an average of what two values?

A

pKa (+1) and pKa (-1)

Anything beyond pKa (+1 or -1) we DO NOT CARE. Only can use these two pKa values for pI

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71
Q

In this test, the pH changes over the length of the gel and proteins stop moving when they are uncharged (pH = pI).

A

Isoelectric focusing

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72
Q

If the pH > pI, then the protein is soluble (deprotonated). Most proteins are very soluble at high pH, where the molecules are (POSITIVELY/NEGATIVELY) charged and repel one another.

A

Negatively

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73
Q

If the pH < pI, then the protein is soluble (protonated). At low pH the proteins are soluble because of repulsions due to their (POSITIVE/NEGATIVE) charge.

A

Positive

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74
Q

When pH = pI then the protein has no net charge and the molecules retain regions of positive and negative charge on their surfaces. This results in an increased tendency the protein to _______ and _______ in solution.

A

Aggregate

Precipitate

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75
Q

What is the first law of thermodynamics?

A

Energy is neither created nor destroyed in a closed system.

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76
Q

This type of energy deals with motion and performing work.

A

Kinetic energy

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77
Q

This type of energy deals with the position and the potential to do work.

A

Potential energy

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78
Q

________ energy is the potential energy within chemical bonds.

A

Chemical

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79
Q

At the atomic level, atoms are always in motion (______ energy) and the electric charges of protons and electrons in atoms constantly pull and push at each other (______ energy.

A

Kinetic

Potential

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80
Q

In chemical energy and bonds, they are _______ energy to begin with but when we break the bonds they become more ______ energy because they can be used to do something else.

A

Potential

Kinetic

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81
Q

In a(n) (OPEN/CLOSED) system, energy cannot leave the system.

A

Closed

**i.e., the universe

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82
Q

In a(n) (OPEN/CLOSED) system, energy can be exchanged between the system and its surroundings.

A

Open

**i.e., a cell

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83
Q

What is the second law of thermodynamics?

A

Disorder is increasing

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84
Q

This is the term used when small molecules are assembled into large ones and energy is required.

A

Anabolic

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85
Q

This is the term used when large molecules are broken down into small ones and energy is released.

A

Catabolic

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86
Q

Which type of metabolic reactions create more disorder, catabolic or anabolic?

A

Catabolic – more pieces means more disorder

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87
Q

What is the Gibbs Free Energy Equation?

A

Delta G = Delta H - T (Delta S)

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88
Q

This is the change in available/usable energy (Gibbs free energy).

A

Delta G

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89
Q

This is the change in total energy (enthalpy) in the system.

A

Delta H

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90
Q

This is the change in disorder (entropy).

A

Delta S

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91
Q

Delta G, Delta H, and Delta S are all _____ _____, which means its value depends only on the initial and final values and not the pathway to get there.

A

State functions

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92
Q

Delta G is (POSITIVE/NEGATIVE) if free energy is released.

A

Negative

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93
Q

Delta G is (POSITIVE/NEGATIVE) if free energy is required.

A

Positive

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94
Q

If energy is released from the system, then Delta H is (POSITIVE/NEGATIVE).

A

Negative

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95
Q

In a closed system, Delta H should equal…

A

0

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96
Q

If disorder decreases, then Delta S is (POSITIVE/NEGATIVE).

A

Negative

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97
Q

If disorder increases, then Delta S is (POSITIVE/NEGATIVE).

A

Positive

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98
Q

When Delta G is negative and free energy is released, this is considered an (ENDERGONIC/EXERGONIC) reaction.

A

Exergonic

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99
Q

When Delta G is positive and free energy is required, this is considered an (ENDERGONIC/EXERGONIC) reaction.

A

Endergonic

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100
Q

When Delta G is positive and free energy is required, this is considered an unfavorable (SPONTANEOUS/DRIVEN) reaction.

A

Driven

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101
Q

When Delta G is negative and free energy is released, this is considered a favorable (SPONTANEOUS/DRIVEN) reaction.

A

Spontaneous

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102
Q

When Delta G equals 0, then the reaction is at _______.

A

Equilibrium

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103
Q

What 3 things make up a nucleotide?

A

Phosphate group
Sugar
Nitrogenous base

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104
Q

When a nucleic acid has no phosphate, it’s called a…

A

Nucleoside

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105
Q

When a nucleic acid has a phosphate, it’s called a…

A

Nucleotide

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106
Q

(DNA/RNA) has a hydrogen on the 2’ carbon.

(DNA/RNA) has a hydroxyl on the 2’ carbon.

A

DNA

RNA

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107
Q

The 1’ carbon is where the base attaches, forming a _______ bond.

A

Glycosidic

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108
Q

The 3’ and 5’ carbons are where ________ bonds form.

A

Phosphodiester

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109
Q

The 4’ carbon contains an _______ within the sugar ring.

A

Oxygen

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110
Q

In a sugar pucker, it can be either C-3’-endo or C-2’-endo. This means the _____ carbon sticks up slightly, or the _____ carbon sticks up slightly.

A

3’

2’

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111
Q

The nitrogenous bases can either be a ______ or ______.

A

Purine

Pyrimidine

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112
Q

Purines have (ONE/TWO) rings, and pyrimidines have (ONE/TWO) rings.

A

Two

One

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113
Q

Which nitrogenous bases are purines?

A

Adenine
Guanine

***PUre As Gold

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114
Q

Which nitrogenous bases are pyrimidines?

A

Cytosine
Thymine
Uracil

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115
Q

Uracil is only present in (RNA/DNA) and takes the place of (CYTOSINE/THYMINE).

A

RNA

Thymine

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116
Q

In DNA, purines ALWAYS base-pair with pyrimidines. Which nitrogenous bases pair with which?

A

A - T

G - C

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117
Q

How many hydrogen bonds are there between A - T?

How many between G - C?

A

2 hydrogen bonds

3 hydrogen bonds

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118
Q

DNA is an _______ double helix running in the 5’ to 3’ direction.

A

Antiparallel

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119
Q

In vitro oligonucleotide synthesis proceeds in what direction?

A

3’ to 5’

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120
Q

Whether a nitrogenous base is _____ or _____ means that is faces inward or outward.

A

Syn

Anti

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121
Q

This double helix structure is right-handed, has a wide and deep major groove, and narrow and shallow minor groove.

A

B-form

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122
Q

The B-from helix has a ______ sugar pucker and _____ nitrogenous base orientation.

A

C2’-endo

Anti

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123
Q

This double helix structure is right-handed, has a narrow and deep major groove, and wide and shallow minor groove.

A

A-form

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124
Q

The A-form helix has a ______ sugar pucker and ______ nitrogenous base orientation.

A

C3’-endo

Anti

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125
Q

This double helix structure is left-handed, has a flat major groove, and a narrow and deep minor groove.

A

Z-form

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126
Q

The Z-form helix has a _____ (pur) and _____ (pyr) sugar pucker and _____ (pur) and _____ (pyr) nitrogenous base orientation.

A

C2’-exo
C2’-endo
Syn
Anti

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127
Q

What helical structure is the physiological DNA form?

A

B-form

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128
Q

What helical structure is primarily seen in RNA?

***RNA can be double stranded if it folds back on itself

A

A-form

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129
Q

What are the 3 possible models for DNA replication?

A

Conservative
Semi-conservative
Dispersive

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130
Q

Hairpins and cruciforms require a ________ sequence (inverted repeat).

A

Palindromic

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131
Q

Hairpins and cruciforms are created by superhelical _____.

A

Strain

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132
Q

A triplex is a 3-stranded DNA that may or may not occur in nature. It requires a ________-_______ duplex and uses Hoogsteen hydrogen bonds.

A

Homopurine

Homopyrimidine

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133
Q

Quadriplexes are 4-stranded DNA that consist of _______ only.

A

Guanine

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134
Q

Quadriplexes occur at what 2 places?

A

Telomeres

Promoters

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135
Q

The melting temperature (Tm) = temperature at which –

  1. Delta G (ds – ss) = 0 (at equilibrium)
  2. Half of sample is ________ (ss)
A

Denatured

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136
Q

How does DNA go from 2 strands to 1?

A

Like a zipper

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137
Q

In tautomers, what is being moved?

A

Hydrogen

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138
Q

DNA has to be (SS/DS) to make tautomers/isomers.

A

SS

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139
Q

Other examples of isomers are the ______ and ______ conformation of nucleic acids.

A

Syn

Anti

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140
Q

Do we prefer syn or anti?

A

Anti

***We don’t like syn but it’s better than having tautomer

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141
Q

How many chances do we have to make a syn/anti isomer?

A

One (Replication fork)

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142
Q

How many chances do we have to make a tautomer?

A

Two (Replication fork and mismatch repair)

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143
Q

What is a transition mutation?

A

Swapping a purine for purine OR pyrimidine for pyrimidine (Still Pur - Pyr pairing)

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144
Q

In a transition mutation, what must one of the BP have?

A

Unfavored tautomer conformation

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145
Q

What is a transversion mutation?

A

Swapping a pyrimidine for purine OR purine for pyrimidine (Now Pur - Pur or Pyr - Pyr)

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146
Q

In a transversion mutation, what do the BP look like?

A

1 is unfavored tautomer and the other is in syn conformation

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147
Q

What is the mutation rate for transitions without proofreading? With proofreading?

A

1x10(-4)

5x10(-9)

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148
Q

What is the mutation rate for transversions without proofreading? With proofreading?

A

2.5-5x10(-6)

1-2.5x10(-10)

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149
Q

What base pair changes to cause sickle cell?

A

A to T (Glu to Val)

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150
Q

Sickle cell is due to _________ of the A.

A

Self-depurination

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151
Q

In the Beta-Globin gene, the self-depurination occurs in codon ______.

A

6

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152
Q

This type of induced mutation, for example, can occur when BrdU pairs with either A or G depending on its chemical state.

A

Base analogs

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153
Q

This type of induced mutation includes mustard gases.

A

Alkylating agents

***Carbons and hydrogens (alkyne, alkene, etc.)

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154
Q

This type of induced mutation is when an agent inserts itself between base pairs in DNA and can cause frameshift mutations.

A

Intercalating agents

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155
Q

This type of induced mutation is when, often a carcinogen, bonds to the DNA through covalent bonds.

A

Adduct-forming agents

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156
Q

________ are intercalating agents that upon activation with UV light form adducts with neighboring pyrimidine residues.

A

Psoralens

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157
Q

Exposure to _______ forms T-T dimers (causes cancer).

A

UV light

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158
Q

In this type of induced mutation, its mutagenic properties are actually a secondary effect: betas, gammas, and x-rays cause electrons to be ejected from an atom, leaving a free radical (free radicals are harmful to the body).

A

Ionizing radiation

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159
Q

List the hydrophobic amino acids.

A
Valine
Alanine
Glycine
Leucine
Isoleucine
Proline
Methionine 
Tryptophan
Phenylalanine
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160
Q

List the polar amino acids.

A
Cysteine
Serine
Tyrosine
Threonine
Asparagine 
Glutamine
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161
Q

List the charged (-) amino acids.

A

Glutamate (Glutamic acid)

Aspartate (Aspartic acid)

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162
Q

List the charged (+) amino acids.

A

Lysine
Arginine
Histidine

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163
Q

What amino acids are tiny?

A

AGCS

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164
Q

What amino acids are small?

A

PNTD

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165
Q

What amino acids are medium?

A

HEVQ

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166
Q

What amino acids are large?

A

MILRK

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167
Q

What amino acids are very large?

A

WFY

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168
Q

What amino acids are very large?

A

WFY

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169
Q

What are the essential amino acids (meaning humans cannot synthesize them)?

A

PVT TIM HALL
(FVW TIM HRKL)

The other 10 humans can synthesize de novo (nonessential amino acids)

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170
Q

_________ amino acids are incorporated into proteins during translation. It includes the 20 usual amino acids, plus 2 more we have to use stop codons to get.

A

Proteinogenic

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171
Q

What is the 21st amino acid and uses the UGA/opal codon?

A

Selenocysteine (Sec, U)

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172
Q

Selenoproteins are important for good health. They reduce ______ _____ in conjunction with Vitamin E. They are required in _______ neurons (growth and coordination), and they moderate _______ responses.

A

Oxidative stress
Cerebellum
Inflammatory

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173
Q

Selenium deficiency results in myopathies, including _______ disease (cardiomyopathy) and ______ intolerance (rhabdomyolysis).

A

Keshan

Statin

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174
Q

If there is too much __________, then you can have hair and nail brittleness, “garlic breath”, gastrointestinal/neurological lesions, myopathies, renal failure, and death.

A

Selenocysteine

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175
Q

What is the 22nd amino acid and uses the UAG/amber codon (present only in some prokaryotes)?

A

Pyrrolysine (Pyl, O)

176
Q

Several members of the intestinal microbiome make/use _____, including types of Archaea and Eubacteria.

A

Pyl

177
Q

__________ amino acids can be used during non-ribosomal protein synthesis (NRPS).

A

Nonproteinogenic

178
Q

Nonproteinogenic amino acids can also be used for ________ (activate carboxyl), _______ (elongation intermediate), ________ (peptide bond formation), and ________ (release or cyclization).

A

Adenylation
Peptidyl Carrier Protein (Thiolation)
Condensation
Thioesterase

179
Q

Nonproteinogenic amino acids can be used to _______ like penicillin or Odilorhabdins.

A

Antibiotics

180
Q

Nonproteinogenic amino acids (ARE/ARE NOT) used to make proteins.

A

Are not

181
Q

The _______ structure of proteins is a chain of amino acids.

A

Primary

182
Q

The _______ structure of proteins is a local folding of the polypeptide chain.

A

Secondary

183
Q

The _______ structure of proteins is folding of the secondary structure.

A

Tertiary

184
Q

The _______ structure of proteins is the interaction of multiple peptides.

A

Quaternary

185
Q

What is the bond name between proteins?

A

Peptide bonds

186
Q

Is a peptide bond a single bond? Can it rotate?

A

Yes, it can rotate because of this

187
Q

The peptide results in a ______ chain with side chains alternating up and down.

A

Planar

188
Q

The ________ interaction is a major factor in the folding and stability of proteins.

A

Hydrophobic

189
Q

Hydrogen bonds are (STRONGER/WEAKER) than covalent bonds and are somehow (LONGER/SHORTER) than covalent bonds. They have energies ranging from 1-5 kcal/mol.

A

Weaker

Longer

190
Q

What are possible secondary structures for proteins?

A

Alpha-helix

Beta-sheet

191
Q

A-helices are stabilized by hydrogen bonds between the ____ and ____ groups. This hydrogen bonds form four amino acid residues ahead in the sequence.

A

NH

C=O

192
Q

In an alpha-helix each aa residue is related to the next one by:

  • A rise of ____ angstroms along the helix axis
  • A ____ degree rotation
  • A ____ aa residue per turn of helix
A

1.5
100
3.6

193
Q

The screw sense of an alpha-helix can be _____-handed (clockwise) or _____-handed (counterclockwise).

A

Right

Left

194
Q

Alpha-helices found in proteins are (LEFT/RIGHT)-handed because they are energetically more favorable.

A

Right

195
Q

Beta-sheets are composed of two or more polypeptide chains, called ______ ______.

A

Beta-strands

196
Q

Beta-sheets are fully extended and the distance between adjacent amino acids along a Beta-strand is about ___ angstroms.

A

3.5

197
Q

A Beta-sheet is formed by linking two or more Beta-strands via ________ bonds.

A

Hydrogen

198
Q

Beta-sheets can run ________ or ________ directions.

A

Parallel

Antiparallel

199
Q

Most Beta-sheets are found in ________ proteins (i.e., hair).

A

Structural

200
Q

Reversal directions provide compact and globular shapes for polypeptide chains. These are called…

A

Reverse turns
Beta-turns
Hairpin turns

201
Q

In many reverse turns, _____ groups and ____ groups form hydrogen bonds for stability.

A

C=O

N-H

202
Q

Loops (i.e., Omega loops) do not have regular periodic structures. They are often well defined and rigid, and positioned on the surface of the protein. They participate in _______-______ interactions and interactions with other ________.

A

Protein-protein

Molecules

203
Q

An alpha-helical coiled coil is called a ________.

A

Superhelix

204
Q

A superhelix provides proteins long fibers. They serve as a ________ role (i.e., alpha-keratin, collagen cell cytoskeleton, muscle proteins) and are involved in _________ functions (i.e., regulation of genes expression, oncoproteins).

A

Structural

Biological

205
Q

The two helices in alpha-keratin (superhelix) associate with each other by weak interactions such as…

A

Van der Waals forces

Ionic interactions

206
Q

A superhelix is characterized by a central region of _____ amino acids that contain heptad repeats. This provides two alpha-helices interact with one another.

A

300

207
Q

Protein folding is a highly _________ process.

A

Cooperative

208
Q

Bovine insulin consists of 2 chains (alpha-chain and beta-chain), linked by 2 interchain ______ bonds. The alpha-chain also has an intra-chain ______ bond.

A

Disulfide

Disulfide

209
Q

Extracellular proteins often have several _______ bonds.

Intracellular proteins usually lack _______ bonds.

A

Disulfide

Disulfide

210
Q

The ______ ______ refers to –

1) Rapid formation of secondary structure
2) Formation of domains through cooperative aggregation
3) Formation of assembled domains (‘molten globule’)
4) Adjustment of conformation
5) More rigid structure

A

Folding funnel

211
Q

Is the entropy higher at the denatured or native state of proteins?

A

Denatured

212
Q

Is energy higher at the denatured or native state of proteins?

A

Denatured

213
Q

There can be repeating motifs in a protein chain, an example being ________, a calcium sensor that contains four similar units in a single polypeptide chain.

A

Calmodulin

214
Q

There can be alternative conformations of peptide sequence. Many sequences can adopt alternative conformations in different proteins. For example, the sequence VDLLKN could an _______ in one protein and a _______ in another.

A

Alpha-helix

Beta-strand

215
Q

________ exists in two conformations, which are in equilibrium (the Chemokine structure and the Glycosaminoglycan-binding structure).

A

Lymphotactin

216
Q

The ______ ______ state is an intermediate conformational state between the native and the fully unfolded states of a globular protein.

A

Molten globule

217
Q

Globular are more (ALPHA/BETA) and molten are more (ALPHA/BETA).

A

Alpha

Beta

218
Q

Molten globule state characteristics include:

1) The presence of a native-like content of _______ structure.
2) The absence of a specific _______ structure produced by the tight packing of amino acid side chains.
3) Compactness in the overall shape of the protein molecule, with a _______ 10 to 30% larger than that of the native state (not packed so tightly).
4) The presence of a loosely packed ________ core that increases the hydrophobic surface area accessible to solvent.
5) It is not specific and occurs in early stage of protein folding.

A

Secondary
Tertiary
Radius
Hydrophobic

219
Q

The molten globule is a compact globule with a “molten” side-chain structure that is primarily stabilized by nonspecific ________ interactions.

A

Hydrophobic

220
Q

What is the equation to calculate the frequency of aa residues in secondary structures?

A

f = aa in a-helix
—————–
All aa

221
Q

What is the equation for the propensity/natural inclination (P) to predict secondary structures in proteins?

A

P = f
———-
All aa

222
Q

A ________ structure is the spatial arrangement of amino acid residues that are far apart in the sequence and to the pattern of disulfide (S-S) bonds.

A

Tertiary

223
Q

What is an example of a tertiary structure?

A

Myoglobin (heme group)

224
Q

______ ______ ______ rearranges the polypeptide’s non-native S-S bonds.

A

Protein disulfide isomerase (PDI)

225
Q

Proteins can be can be denatured by several treatments to disrupt the tertiary structure. The protein folding and unfolding is an “________” process.

A

All-or-none

226
Q

The molten globule stage is intermediate and very ______.

A

Short

227
Q

A partial loss of folding ________ the remainder of the structure. The structural properties of proteins provide a clear rationale for the cooperative transition.

A

Destabilizes

228
Q

A ________ structure is the spatial arrangement of subunits and nature of their interaction.

A

Quaternary

229
Q

What is an example of a quaternary structure?

A

Hemoglobin (2 alpha-subunits, 2 beta-subunits)

230
Q

This accessory protein interconverts cis and trans isomers of peptide bonds with the aa proline.

A

PPI (peptidyl prolyl cis-trans isomerases)

231
Q

HSP 70 (HSP 40) are a type of _________ that are ATP-driven and function to reverse misfolds, check newly synthesized proteins, and unfold/refold trafficked proteins.

A

Chaperones

232
Q

This type of accessory protein is a type of chaperone and provides favorable conditions for correct folding of proteins, a protein folding container.

A

Chaperonins

233
Q

These were the 1st ever discovered chaperones in the nucleosome.

A

Nucleoplasmins

234
Q

This type of chaperone is for signal transduction proteins.

A

HSP 90

235
Q

Protein denaturation can be caused by certain conditions, including…

A

Heat
pH (extremes)
Agitation (forms precipitate)

236
Q

Protein denaturation can be caused by certain chemicals, including…

A

Detergents (SDS) **Breaks disulfide bridges

Chaotropic agents (urea, guanidine hydrochloride **which disturbs hydrogen bonds)

Organic solvents (TCA) [Trichloroacetic acid] **Disturbs hydrogen bonds

237
Q

What are 5 methods of analysis of protein denaturation?

A
Turbidity (cloudiness)
Circular Dichroism (CD) 
UV absorption
Fluorescence
Biological activity (such as receptors, i.e., insulin)
238
Q

This is a differential absorption of right-hand and left-hand circularly polarized light resulting from molecular asymmetry involving a chromophore group. It’s used to study the conformation of proteins in solution.

A

Circular dichroism (CD)

239
Q

Molecure _______ are essential proteins that bind to unfolded and partially folded polypeptide chains. They prevent the improper association of exposed hydrophobic segments. Non-native folding, polypeptide aggregation, and precipitation will not occur.

A

Chaperons

240
Q

These allow misfolded proteins to refold into their native conformation.

A

Chaperons

241
Q

There are 2 major classes of chaperons, which are…

A

Heat Shock Proteins (HSP)

Chaperonins

242
Q

This family of HSP coordinates cellular function by directing substrates for unfolding, disaggregation, refolding or degradation.

A

HSP 70

243
Q

This family of HSP integrates signaling functions, acting at a late stage of folding of substrates.

A

HSP 90

244
Q

These proteins are types of chaperonins (protein folding containers).

A
HSP 60 (GroEL)
HSP 10 (GroES) (co-chaperone)
245
Q

Protein turnover is tightly regulated. They can either be stable (long life) like _______ (120 days) or be short-lived (participates in metabolic regulation) like ______ ______ (11 minutes).

A

Hemoglobin

Ornithine carboxylase

246
Q

Cells must remove aged proteins as well as damaged proteins. A number of pathological diseases are associated with protein ________.

A

Aggregation

247
Q

This is a protein degradation machine, a large protease complex. It’s part of the protein homeostasis system.

A

Proteasome

248
Q

Proteasomes digest _________ proteins.

A

Ubiquinated

249
Q

A _____ proteasome has 2 _____ regulatory unites and one _____ catalytic core.

A

26S
19S
20S

250
Q

In the 26S proteasome, this part recognizes ubiquinated proteins. Isopeptidase cleaves off the ubiquitin, and it directs the protein into the catalytic core.

A

19S regulatory unit

251
Q

In the 26S proteasome, this part is composed of 28 subunits. It is a catalytic core composed of a sealed barrel. Access is controlled by 19S.

A

20S catalytic core

252
Q

The proteasome and other proteases generated _____ amino acids. Ubiquinated proteins are processed to peptide fragments. Peptide fragments are further digested to yield _____ amino acids. These can be used for biosynthetic reaction.

A

Free

Free

253
Q

The _______ method is an empirical technique for the prediction of secondary structures in proteins.

A

Chou-Fasman

254
Q

Cellular quality control systems include…

A

Proteasomes
Autophagy
ERAD (ER-Associated Degradation)

255
Q

Maintenance of protein homeostasis is _______.

A

Critical

256
Q

This is what occurs when mutant CFTR (in cystic fibrosis) and Beta-glucosidase (in Gaucher’s disease) are degraded through ERAD (endoplasmic reticulum associated degradation). These mutant proteins still retain partial functionality, which is still better than no protein at all. So the degradation is harmful.

A

Improper degradation

257
Q

This is what occurs when AAT (alpha1-antitrypsin) does not fold properly. Normally, it is produced in the liver and gets transported to the lungs. When it is mutated the AAT is not transported to the lungs, causing the lungs to not do their job. This is called a ______ _____ ______. Since AAT cannot be moved to the lungs, it stays in the liver and aggregates. This is called a ______ _____ ______ _______.

A

Improper localization
Loss-of-function
Gain-of-function toxicity

258
Q

This is a type of mutation that occurs when a mutant protein antagonizes the function of the WT protein. There is a loss of protein activity and the mutant protein presence interferes with the function of the WT protein at the cellular and structural levels. The examples used were keratin and p53. Each one have multiple subunits. If one subunit was mutated and the rest were normal, that mutant would take dominance and effect the whole structure.

A

Dominant Negative Mutations

259
Q

This occurs when a protein conformational change can cause a dominant phenotype. Proteins become toxic. For example, APOE4 is a variant of APOE in Alzheimer’s disease. This one change can cause mitochondrial disfunction and impair neurite outgrowth. Another example is Src kinases in cancer.

A

Gain-of-Toxic Function

260
Q

These are insoluble protein aggregates.

A

Amyloid fibers

261
Q

Amyloidogenic proteins have a _______ sequence, which can cause amyloid-related diseases.

A

VQIVY

262
Q

Several amyloidogenic proteins form a pore-like structure and can disrupt the _____ _____ integrity.

A

Cell membrane

263
Q

Misfiled forms of the protein are frequently observed in the elderly, as part of the natural aging process, and individuals with mutations in the protein early in life. A common result of amyloid fiber production are _______ in elderly (usually).

A

Cataracts

264
Q

How does the amyloid progress to amyloid plaques?

A

Seeding (nucleation)
Fibril formation
Deposit

265
Q

________ modifications enhances the formation of amyloid fibers.

A

Covalent

266
Q

Understanding more about how misfolded proteins contribute to disease opens new avenues for drug discovery. For example, TTR (transthyretin protein) has four identical polypeptides. It is a primary carrier of hormone thyroxine and a retinol transporter, and is also amyloidogenic. We could block the aggregate formation by:

1) Using small molecules, such as ________
2) _____-_____ ______ (these recognized conformational changes and are sequence specific, such as VQIVY)

A

Stabilizer

Site-specific antibodies

267
Q

The organism maintains its capacity to grow and reproduce. Keystones for environmental stressors are…

A

To detect
To respond
To adopt
(DRA)

268
Q

Intrinsic induction of stress defense programs and resulting adaptation can (INCREASE/DECREASE) life expectancy.

A

Increase

269
Q

Applying moderate levels of stress could trigger beneficial and adaptive stress defense pathways, allowing a (LONGER/SHORTER) life.

A

Longer

270
Q

_______ restriction prolongs the lifespan.

A

Caloric

271
Q

This is the term used for the maintenance of “protein homeostasis”.

A

Proteostasis

272
Q

Cellular and organismal functionality requires protein protein _______, _______, and _______.

A

Production
Folding
Degradation

273
Q

_____ _____ _____ are complex pathways to ensure proteostasis in different compartments such as the cytosol (HSR), the ER (UPRer), and mitochondria (UPRmt).

A

Unfolded protein responses (UPR)

274
Q

Cellular proteins are folded by _______.

A

Chaperones

275
Q

Membrane and secreted proteins fold and mature in the _____.

A

ER

276
Q

A specific response helps to cope with misfolded protein accumulation. The _______ pathway is the last line of defense.

A

Apoptotic

277
Q

This manages denatured proteins in the cytosol (HSF1).

A

Heat Shock Response (HSR)

278
Q

This is the ER stress initiated signal pathway.

A

UPRer

279
Q

This is the mitochondria initiated signal pathway.

A

UPRmt

280
Q

If unfolded or misfolded proteins accumulate in the ER, it causes ER stress. ER stress imitates a signal pathway called unfolded protein response (UPR). This pathway is intended to save the cell. UPR tries to do this by:

1) Increase protein ________
2) Increase rate of ______
3) Decrease _______ production
4) ________ as a last resort when other methods of reducing ER stress fail

A

Chaperones
ERAD
Protein
Apoptosis

281
Q

______ _____ _____ proteases are specific for each mitochondrial compartment. They recognize and degrade the proteins that don’t fold and properly assemble. ______ sense the overload of this system’s capacity and activates the transcription of nuclear encoded protective genes. This reestablishes the mitochondrial homeostasis.

A

Protein quality control (PQC)

UPRmt

282
Q

This is the term for an interdisciplinary field that set computational tools for understanding biological data. It combines biology, computer science, information engineering, mathematics and statistics to analyze and interpret biological data.

A

Bioinformatics

283
Q

This is the term for the study of proteins.

A

Proteomics

284
Q

This is the term for the entire set of proteins produced by an organism.

A

Proteome

285
Q

______ are two molecules that are derived from a common ancestor.

A

Homologs

286
Q

______ are homologs present within one species that have a common origin (a duplication event) but may have evolved different functions.

A

Paralogs

287
Q

______ are homologs that are present in different species and that have similar functions.

A

Orthologs

288
Q

Sequence comparisons must rule out the possibility that the similarities are due to chance. Sequences are systematically aligned to search for similarities, a process called ______ ______. The similarity of alpha-hemoglobin and myoglobin can be compared.

A

Sequence alignment

289
Q

Sequence identities can be established by sliding one sequence past the other and counting the number of ______. The two alignments with the largest number of matches are shown (slide 8). This plots the alignment with the greatest number of matches across all of the potential alignments.

A

Matches

290
Q

Searching for sequence identities sometimes yields multiple alignments that display a large number of matches. Introduction of a _____ into one of the sequences may allow identities found in the different alignments to be represented in one alignment. However, the use of _____ may generate artificial similarities.

A

Gap

Gaps

291
Q

Scoring systems facilitate the use of gaps. For instance, 10 points are assigned for a match and 25 points are _______ for a gap.

A

Deducted

292
Q

Myoglobin and alpha-hemoglobin are 25.9% identical with a score of 355. The score is (LOW/HIGH), this means we know their origin is similar.

A

High

293
Q

The significance of an alignment can be assessed by randomly rearranging the sequence of one of the sequences being compared. The _______ sequences are used in the sequence alignment process and the alignment scores are determined. If the original score is not sufficiently different from the randomized score, the original alignment could be a result of ______.

A

Shuffled

Chance

294
Q

Alignment scores are calculated for many shuffled sequences, and the number of sequences generating a particular score is plotted agains the score. The resulting plot is a distribution of alignment scores occurring by chance. The alignment score for unshuffled alpha-hemoglobin and myoglobin is substantially greater than any of these scores, strongly suggesting that the sequence similarity (IS/IS NOT) significant.

A

Is

**See slide 12

295
Q

A more sensitive scoring system takes into account the degree of similarity of amino acids. A ________ substitution replaces one amino acid with a similar one. A ________ substitution replaces one amino acid with one with different chemical properties.

A

Conservative

Nonconservative

296
Q

Amino acid substitutions can also be classified by the fewest number of ________ changes to achieve the amino acid substitution.

A

Nucleotide

297
Q

A substitution matrix, such as _______, is a scoring system that awards points for substitutions that are commonly found in nature and subtracts points for substitutions that only rarely occur. The substitution matrix shows that many of the differences between alpha-hemoglobin and myoglobin are conservative.

A

Blosum-62 (Blocks Substitution Matrix)

298
Q

Substitution matrices can reveal ________ not identified by sequence alignments only.

A

Homologies

299
Q

The Blosum-62 indicates that a conservative substitution (i.e., lysine for arginine) receives a (POSITIVE/NEGATIVE) score, whereas a nonconservative substitution (i.e., lysine for tryptophan) is scored (POSITIVE/NEGATIVE).

A

Positive

Negative

300
Q

The use of Blosum-62 yields the alignment shown between human myoglobin and lupine leghemoglobin illustrating _______ and _______ substitutions. These sequences are 23% identical. Leghemoglobin is an oxygen carrier and hemoprotein found in the nitrogen-fixing root nodules of leguminous plants.

A

Identities

Conservative

301
Q

In order to detect sequence similarities between proteins or nucleic acids, ______ searches are performed. The sequence under investigation is entered into the database, and a ______ search yields a list of sequence alignments accompanied by an estimate that the alignments occurred by chance.

A

BLAST
BLAST

**(Basic Local Alignment Search Tool)

302
Q

Tertiary structure is more closely associated with function than is primary structure. Plant leghemoglobin shows little sequence homology with other globins but is remarkably similar in ______.

A

Structure

303
Q

On the basis of three-dimensional structure, actin and Hsp70, proteins with different biological functions, are _______.

A

Paralogs

304
Q

Knowledge of 3D structures can aid in the evaluation of sequence alignments. A _______ _______, a map of conserved sequences that are structurally and functionally important and are common to a particular family of proteins, allows the detection of homologs that may not be apparent with other techniques.

A

Sequence template

305
Q

T/F. Repeated motifs can be detected by aligning sequences with themselves. Many proteins have domains that are similar to one another. Such repeats are detected by performing sequence alignments with the protein itself.

A

True

306
Q

_______ evolution is an example of proteins from different evolutionary pathways arriving at the same solution to a biochemical problem. Some proteins have common structural and functional features but do not share a common ancestor. An example of this evolution are serine proteases.

A

Convergent

307
Q

Proteins derived from a common ancestor are a result of ________ evolution.

A

Divergent

308
Q

Comparison of RNA sequences can be a source of insight into RNA ________ structures.

A

Secondary

309
Q

The lengths of the branches of _______ ______ connecting two proteins are proportional to the number of differences in the amino acid sequences of the two proteins. For example, Hemoglobin form lamprey (whose ancestors diverged from bony fish approx. 400 million years ago) consists of only a single type of subunit.

A

Evolutionary trees

310
Q

_____ _____ _____ is the exchange of DNA between species that confers selective advantage on the recipient. It is common among prokaryotes. This may explain unexpected branches of the evolutionary tree.

A

Horizontal gene transfer

311
Q

The polymerase chain reaction and DNA sequencing technology make it possible to determine the sequence of _______ DNA. Comparison of DNA sequences revealed that neither Neanderthals nor Denisovans are on the line of direct descent leading to Homo sapiens but, instead, branched off earlier and then became extinct.

A

Ancient

312
Q

The use of ________ chemistry makes it possible to observe molecular evolution in laboratory.

A

Combinatorial

313
Q

Three criteria are required to mimic evolution –

1) A ______ population.
2) Selective pressure to allow ______ to be evident.
3) ________ that permits the enrichment of fit individual molecules.

A

Diverse
Fitness
Reproduction

314
Q

This is an interdisciplinary field that uses computers and information technology to gain, store, analyze, communicate and display medical information and knowledge. This aids the understanding and evaluation of clinical information and improves accuracy, quickness and reliability of decision making. The main aims are to reduce medical risks, improve patient care and cut costs of treatment.

A

Medical bioinformatics

315
Q

______ facilitates access to and communication about the relationships asserted between human variation and observed health status, and the history of that interpretation.

A

ClinVar

316
Q

One component used to evaluate the potential significance of a nucleotide or amino acid variant is to examine its ________ over evolutionary history.

A

Conservation

317
Q

______ extracts and prioritizes patient phenotypes directly from medical records to expedite genetic disease diagnosis.

A

ClinPhen

318
Q

_____ _____ is a general term that implies the use of a computer to model intelligent behavior with minimal human intervention. In medicine, it has two main branches: ______ and _______.

A

Artificial intelligence (AI)
Virtual
Physical

319
Q

The (PHYSICAL/VIRTUAL) branch of AI includes informatics approaches from deep learning information management to control of health management systems, including electronic health records, and active guidance of physicians in their treatment decisions.

A

Virtual

320
Q

The (PHYSICAL/VIRTUAL) branch of AI is best represented by robots used to assist the elderly patient or the attending surgeon.

A

Physical

321
Q

This type of enzyme moves electrons (redox reactions). Examples of activated carriers include: NADH, NADPH, FADH2, and FMNH2.

A

Oxidoreductases

322
Q

This type of enzyme moves a functional group (group transfer). Activated carriers include: ATP, pyridoxal phosphate, SAM, Tetrahydrofolate, and 5’-deoxyadenosylcobalamin.

A

Transferases

**ATP and pyridoxal phosphate transfer phosphate groups

**SAM, Tetrahydrofolate, and 5’-deoxyadenosylcobalamin transfer methyl groups

323
Q

This type of enzyme breaks a chemical bond by adding water across it (hydrolysis).

A

Hydrolases

324
Q

This type of enzyme rearranges the order of atoms in a molecule (isomerization).

A

Isomerases

325
Q

This type of enzyme breaks a chemical bond without using water.

A

Lyases

326
Q

This type of enzyme pastes two pieces together (make a chemical bond), uses ATP.

A

Ligases

327
Q

For ligases and lyases, TPP can be an activated carrier because it adds or subtracts an _______ group.

A

Aldehyde (-COH)

328
Q

For ligases and lyases, CoASH and lipoamide can be activated carriers because they either add or subtract ______ groups.

A

Acyl (-COR)

329
Q

For ligases and lyases, biotin can be an activated carrier because it adds or subtracts a _____ group.

A

CO2

330
Q

In a nucleophilic substitution reaction we swap…

A

Functional groups

331
Q

In a nucleophilic addition reaction we add…

A

Functional groups

332
Q

In a carbonyl condensation reaction we change the number of…

A

Carbons

333
Q

In an elimination reaction we increase the ______ order.

A

Bond

334
Q

In an oxidation-reduction reaction we move…

A

Electrons

335
Q

This is a site on a protein that is only a few residues. It is a 3D cleft/crevice/pocket, creating a unique environment. It determines substrate specificity by size and charge complementarity and contact with the substrate through non covalent interactions.

A

Active site

336
Q

This type of binding does NOT occur at the binding site, but follows the same interaction rules. It involves a second substrate, which can be an activator or an inhibitor.

A

Allosteric binding

337
Q

This type of inhibition occurs when an inhibitor binds to the active site, keeping the other substrates from getting to it.

A

Competitive inhibitor

338
Q

This type of inhibition occurs when a substrate binds to another site on the enzyme, changing the shape of the active site. This now keeps the substrate from binding to the active site.

A

Allosteric inhibitor

339
Q

This type of activator binds to another site on the enzyme, which causes the enzyme to change shape to fit the wanted substrate or become more desirable to that substrate.

A

Allosteric activator

340
Q

T/F. Competitive activation exists.

A

False. Not a thing!

341
Q

This type of enzyme is incomplete, inactive, and lacks a cofactor/coenzyme.

A

Apoenzymes

342
Q

This type of enzyme is whole, active, and contains a cofactor/coenzyme. It requires allosteric activation!

A

Holoenzymes

343
Q

If an enzyme has more than one binding site, the sites can be –

  • _____ equivalent _____ independent
  • _____ equivalent _____ independent
  • _____ equivalent _____ independent
A

All; And
Either; Or
Neither; Nor

344
Q

Kd is the dissociation constants for ExSn complexes. It is equal to the concentration of ligand where half the available binding sites are full OR you can say it is when the ______ is half-saturated.

A

Receptor

345
Q

For n=1, when Y (fractional saturation) equals 0 that means No ligand is bound. When Y=1 it means the receptors is saturated. When Y=0.5 it means the receptor is _______.

A

Half-saturated

346
Q

This is the term for when the binding of each subsequent ligand influences the affinity (strength of interaction) of the next ligand to bind an active site.

A

Cooperativity

347
Q

In terms of cooperativity, we interpret Hill Coefficients in the following way:

  • nH=1 means NO cooperativity (sites are independent)
  • nH > 1 means (POSITIVE/NEGATIVE) cooperativity (affinity increases)
  • 0 < nH < 1 means (POSITIVE/NEGATIVE) cooperativity (affinity decreases)
A

Positive

Negative

348
Q

The function of _______ are to transport oxygen from the lungs to the tissue. Hemoglobin occupies 33% of the volume of these.

A

Erythrocytes

349
Q

65% of hemoglobin is synthesized before extrusion of the nucleus. _______ makes the remaining 35% of Hb required for the RBC.

A

Reticulocytes

350
Q

There is a ______ phenomenon as to where red blood cells are made during development.

A

Switch

351
Q

Hemoglobin is a multi-subunit protein (tetramer). It contains 2 _____ globin chains and 2 _____ globin chains.

A

Alpha

Beta

352
Q

There is one of these per subunit of hemoglobin. It has the iron atom that carries oxygen.

A

Heme

353
Q

Hemoglobin also has four _________ IX rings.

A

Protoporphyrin

354
Q

There are 3 types of hemoglobin in humans, including…

A

Embryonic
Fetal
Adult

355
Q

There are 4 types of globin chains in the normal adult, including…

A

Alpha
Beta
Delta
Gamma

356
Q

The predominant form of Hb in the human adult is _____ which has 2 alpha and 2 beta subunits.

A

HbA

357
Q

In the adult about 97% is HbA, about 3% is another Hb called HbA2 composed of 2 _____ and 2 _____ subunits. Another 0.5% is fetal hemoglobin (HbF).

A

Alpha

Delta

358
Q

Fetal Hb is composed of 2 _____ and 2 _____ subunits.

A

Alpha

Gamma

359
Q

The globin proteins have alpha-like chains and beta-like chains. What falls under alpha-like chains? Beta-like chains?

A

Zeta (embryonic)
Alpha

Epsilon (embryonic)
Gamma (fetal)
Delta
Beta

360
Q

Chromosome ____ has Beta globin genes (epsilon, gamma with glycine, gamma with alanine, delta, beta) and chromosome ____ has alpha globin genes (zeta, alpha 1, alpha 2).

A

11

16

361
Q

Embryonic Hb is expressed in the ____ ____ but not after 8 weeks gestation. Embryonic Hb is 2 _____ and 2 _____ subunits.

A

Yolk sac
Zeta
Epsilon

362
Q

Fetal Hb is made predominantly in the ______ (and ____ ____). In the fetus, HbF is 90-95% total Hb production until 34-36 weeks gestation.

A

Liver

Bone marrow

363
Q

After birth, adult Hb production starts. In a newborn 50-85% Hb is still HbF, and at _____ of life HbA reaches adult levels.

A

1 year

364
Q

At amino acid position #6 in Beta globin there is a substitution of valine for glutamic acid, this is called ______. It causes polymerization of Hb.

A

HbS (sickle cell)

365
Q

Research is ongoing to induce expression of ____ to help with sickle cell. We’re currently using hydroxyurea to induce it and address inflammation but this is a chemotherapeutic agent.

A

HbF

366
Q

Research is ongoing to induce expression of ____ to help with sickle cell. We’re currently using hydroxyurea to induce it and address inflammation but this is a chemotherapeutic agent.

A

HbF

367
Q

Globin genes are arranged in _______ fashion. Ordered in the 5’ to 3’ direction in the same sequence of activation and expression during embryonic, fetal and adult development.

A

Linear

368
Q

In hemoglobin, this is a prosthetic group and non-amino acid group of a protein.

A

Heme

369
Q

Heme gives blood its color, transports _______ and releases it where it is needed.

A

Oxygen

370
Q

The heme is nestled in a _______ crevice of the protein chain.

A

Hydrophobic

371
Q

75% of globin chain forms ______.

A

Alpha-helix

372
Q

The heme group consists of an organic component and a central ______ atom.

A

Iron

373
Q

The organic component of heme is called _________.

A

Protoporphyrin

374
Q

Protoporphyrin is made up of four ________ rings.

A

Pyrrole

375
Q

Pyrrole is characterized by a ring structure composed of four ______ atoms and one ______ atom.

A

Carbon

Nitrogen

376
Q

Four pyrrole rings form a _______ ring.

A

Tetrapyrrole

377
Q

In heme, four ______ groups, two ______ groups, and two _______ side chains are attached. The iron atom lies in the center of the protoporphyrin, bonded to the four pyrrole nitrogen atoms.

A

Methyl
Vinyl
Propionate

378
Q

There are 8 helical segments to a globin subunit and they are labeled ____ through ____.

A

A

H

379
Q

Amino acids are named according to the helical segment and # amino acid in that segment (i.e., F8 Histidine is the 8th residue in the F helix). What segment # is D in the globin subunit?

A

4th

380
Q

The F8 Histidine is called the (PROXIMAL/DISTAL) histidine which is bound to the heme group (6th segment in globin chain).

A

Proximal

381
Q

The E7 Histidine is called the (PROXIMAL/DISTAL) histidine and oxygen binds to the iron between the heme and distal histidine (5th segment in globin chain).

A

Distal

382
Q

A ______ bond donated by the histidine E7 residue to the bound oxygen molecule helps stabilize oxyhemoglobin.

A

Hydrogen

383
Q

In hemoglobin, oxygen binding changes the position of the ____ atom by 0.4 angstroms. This pulls the F8 proximal histidine which is attached to the globin chain and moves into the plane of the heme.

A

Iron

384
Q

Upon _______, the iron atom moves into the plane of the heme and pulls the proximal F8 histidine residue of hemoglobin. This is incredibly important for the function of hemoglobin.

A

Oxygenation

385
Q

Myoglobin is a _______ encoded by a different gene than the globin genes (Chr 22).

A

Monomer

386
Q

Myoglobin has _____ heme-Fe2+ group.

A

One

387
Q

Myoglobin is an oxygen (STORAGE/TRANSPORTER) protein and hemoglobin is an oxygen (STORAGE/TRANSPORTER) protein.

A

Storage

Transporter

388
Q

Myoglobin is very common in ______ cells. Its job is to store oxygen, for use when ______ are hard at work.

A

Muscle

Muscles

389
Q

Hb function is to transport oxygen from the ______ to the tissues via ______.

A

Lungs

Blood

390
Q

4 heme molecules can carry ______ O2 (oxygen).

A

4

391
Q

Myoglobin has (LOW/HIGH) affinity for oxygen. It holds onto it tightly, hence why it’s a storage protein.

A

High

392
Q

T/F. The 0.4 angstrom change induced by binding of oxygen to Fe and pulling down of F8 histidine means little for myoglobin. It’s important to hemoglobin.

A

True

393
Q

Oxygen _______ ______ presents saturation of myoglobin with oxygen at different concentrations of oxygen (measured in Torr-mmHg)

A

Dissociation curve

394
Q

Half the myoglobin molecules have bound oxygen when the oxygen partial pressure is ____ torr.

A

2

395
Q

In RBC the Hb curve is shaped like an “S”, or sigmoid shape. Hb switches between 2 states of affinity, _____ and _____.

A

High

Low

396
Q

Binding to oxygen must be _______. Hb is the ultimate “switch hitter”, it can bind oxygen with high affinity and let go with low affinity.

A

Reversible

397
Q

Hb picks up oxygen in the lungs at a pressure of 100 mmHg and is _____ saturated. Hb drops oxygen off in the tissues at about 10 to 20 mmHg and is only about _____ saturated. Sigmoidal shape is the result of interactions between the globin subunits.

A

100%

20%

398
Q

Myoglobin has high affinity for oxygen and doesn’t release oxygen until pressure in tissues is very (HIGH/LOW).

A

Low (close to 0 Torr)

399
Q

P50 is the oxygen partial pressure at which molecule is half saturated with oxygen. P50 Myoglobin = ______ and P50 Hb = _____.

A

2.8 Torr

26 Torr

400
Q

Hb binds oxygen in a _______ fashion, meaning as soon as one molecule of oxygen binds to one heme, it facilitates the binding of an oxygen to another heme.

A

Cooperative

401
Q

T/F. Conformational change in one globin subunit induces a conformational change in another subunit in Hb. Hb’s conformation, hence its oxygen affinity, changes as each successive molecule of oxygen is bound.

A

True

402
Q

The binding of oxygen to iron of a globin subunit pulls the proximal F8 histidine. This pulls on the globin alpha-helix chain and changes the interaction with the other globin chains in Hb. This changes the organization of other globin chain and their affinity for oxygen. ________ occurs.

A

Cooperativity

403
Q

Hypothetically if there was no cooperativity, Hb would not be a good _______ carrier.

A

Oxygen

404
Q

T/F. As Hb loses oxygen in the tissue, the loss of an oxygen molecule by a globin subunit makes it more likely the next subunit will lose its oxygen molecule.

A

True

405
Q

Hb is an allosteric protein. Structure and function are influenced by other molecules: ______, _____, (HbF).

A

2,3-BPG

H+

406
Q

A major modulator of Hb is 2,3-BPG. It is an intermediate by-product of glycolysis. In active tissues there is lots of 2,3-BPG made, it signals to Hb to let go of _______.

A

Oxygen

407
Q

2,3-BPG is present in RBCs at approximately the same concentrations as Hb. Without 2,3-BPG, Hb would be an extremely inefficient ______ transporter.

A

Oxygen

408
Q

Pure Hb (no 2,3-BPG) has a curve that is hyperbolic, like _______. Hb in RBCs with 2,3-BPG has a sigmoid curve that shifts to the right. At 20 Torr pure Hb only gives up 8% oxygen, but Hb gives up 66%.

A

Myoglobin

409
Q

In active tissues there is lots of 2,3-BPG made, which signals to Hb to let go of oxygen. It reduces oxygen affinity so Hb gives up more oxygen to tissues. Cells actively perspiring are metabolizing _______ and will produce this molecule.

A

Glucose

410
Q

In highly metabolizing tissue, you do not want Hb to hold onto oxygen, you want Hb to release oxygen. 2,3-BPG binds to the central pore of deoxyhemoglobin (interacts with 3 positively charged groups). NO 2,3-BPG (lungs) means (LOW/HIGH) affinity for oxygen. High 2,3-BPG (tissues) means (LOW/HIGH) affinity for oxygen.

A

High

Low

411
Q

The ______ or tight form of Hb means low affinity for oxygen.

A

Tense (“T”)

412
Q

The ______ form of Hb means high affinity for oxygen.

A

Relaxed (“R”)

413
Q

In non-oxygenated Hb, beta chains are farther apart. This is the (TENSE/RELAXED) form.

A

Tense

414
Q

In oxygenated Hb, beta chains are closer together. This is the (TENSE/RELAXED) form.

A

Relaxed

415
Q

High 2,3-BPG stabilizes the T form of Hb, (LOW/HIGH) affinity and releases oxygen.

A

Low

416
Q

Low 2,3-BPG in lungs leads to R form, (LOW/HIGH) affinity for oxygen.

A

High

417
Q

2,3-BPG is (HIGHER/LOWER) in smokers. Meaning oxygen carrying capacity is reduced in smokers.

A

Higher

418
Q

The pH of actively respiring tissues is lower, it drops from pH of 7.4 to 7.2. The binding affinity of Hb for oxygen (INCREASES/DECREASES) as the pH decreases. An amino acid picks up H+ from tissue. It changes the conformation of Hb and favors the release of oxygen.

A

Decreases

419
Q

The fetus needs Hb that has a (LOWER/HIGHER) affinity for oxygen than mother’s Hb.

A

Higher

420
Q

Oxygen flows from mother to fetus because HbF does not bind well to _______, therefore it has a higher affinity for oxygen.

A

2,3-BPG

421
Q

HbF is mostly locked in the (TENSE/RELAXED) form because it does not bind well to 2,3-BPG. This signifies a high affinity of oxygen.

A

Relaxed

422
Q

The _______ model of cooperativity is when each level of oxygen loading causes an adjacent globin chain to change from the T to R or vice versa state (One at a time).

A

Sequential

423
Q

The _______ model is when ALL Hb tetramers exist in either the T state or R state (All or nothing).

A

Concerted

424
Q

Carboxyhemoglobin occurs when heme is combined with ______ ______. The bond with this is 210 times stronger than the bond with oxygen. Transport of oxygen to tissues is impaired. Death can occur from overexposure (suffocation).

A

Carbon monoxide

425
Q

______ occurs when a post translational modification of the N-terminus of the Beta-Globin chain occurs. This modification is glycosylation ( addition of glucose) that is irreversible. Usually there is 3% in a normal person but it varies with the level of blood glucose concentration to which RBCs have been exposed to in their 120 day lifespan. It is increased in diabetes by 2x to 3x (6% to 9%) and reflects the control of glucose levels for the last 120 days.

A

HbA1c

426
Q

Hemoglobinopathies include two major types, which are…

A

Structural

Quantitative

427
Q

Structural hemoglobinopathies includes ______ ______ disease. There is a non-functioning globin protein and Beta globin chain defect.

A

Sickle cell

428
Q

Quantitative hemoglobinopathies include ________. This occurs when insufficient globin chains are produced. There is an alpha and beta form, where alpha globin chains are affected or beta globin chains are affected.

A

Thalassemias

429
Q

In alpha-Thalassemia, it involves both alpha globin genes. There is a deletion of 1, 2, 3, or 4 alpha globin genes. If only 1 is deleted then you are a _______. Deficiency of alpha globin chains affects Hb production in both fetal and adult life.

A

Carrier

alpha+-Thalassemia

430
Q

In fetal life, excess zeta globin chains (due to less alpha chains from thalassemia) form zeta 4 tetramers or Hb ______. This variant of Hb is so called as it was discovered at St. Bartholomew’s Hospital in London.

In adults, excess Beta globin chains form Beta4 tetramers or _____. These tetramers precipitate slowly as red cells mature and age. Precipitate forms inclusion bodies (Heinz bodies) which lead to hemolytic anemia.

A

Bart’s

Hb H

431
Q

Traits of alpha-thalassemia includes ________ (low MCV: mean cell volume) and _______ (low MCH: mean cell Hb), and normal percentages of HbA2 and HbF.

A

Microcytosis
Hypochromia

***Occurs when 2 genes are deleted

432
Q

In alpha-thalassemia, _____ disease occurs when 3 alpha genes are affected. This disease is characterized by moderately severe anemia, microcytic, hyochromic hemolytic anemia, hepatosplenomegaly, mild jaundice.

A

Hb H

433
Q

In alpha-thalassemia, _____ _____ with Hb Bart’s occurs when all 4 alpha genes are completely inactivated. This is severe, stillborn or die few hours after birth. Few are saved by exchange transfusion. Fetal onset of generalized edema and severe hypochromic anemia.

A

Hydrops fetalis

434
Q

Hb Bart’s has high affinity for ______. It binds oxygen delivered by mother but releases almost none to fetal tissues. Severe hypoxia occurs and leads to profound edema (hydrops) due to congestive heart failure.

A

Oxygen

435
Q

In beta-thalamessia causes reduced beta chain synthesis and excess alpha chains. These alpha chains precipitate as inclusions and cause damage to red cell precursors and red cells. Leads to profound _______.

A

Anemia

436
Q

There are 2 main varieties of beta-thalamessia. Thalamessia ______ form has no beta-chain expression, severe homozygous condition. Thalamessia _____ form has partial deficiency beta-chains, heterozygous condition with milder anemia.

A

Major

Minor

437
Q

What do the cells look like with severe anemia?

A

Tear drops

Targets