Lecture 1: Fundamentals

Question 1

What is 1st law of thermodynamics?

Answer 1

Energy is neither created nor destroyed; however energy can change form

Question 2

Heat is defined as:

Answer 2

How quickly molecules are moving (kinetics)

Question 3

What is potential energy?

Answer 3

Stored energy (eg. high energy bonds in ATP); energy that will be released when a process occurs

Question 4

The EXTENT of the reaction is described by ______ and the RATE of the reaction is described by _______

Answer 4

Equilibrium; Kinetics

Question 5

What is enthalpy? What is it called when H is < 0 or > 0?

Answer 5

The heat of the reaction. When energy is released or consumed in a chemical reaction, this energy is manifested in form of heat. Exothermic (negative number = gives off heat); Endothermic (positive number = absorbs heat)

Question 6

What is the 2nd law of thermodynamics?

Answer 6

Entropy (S) is always increasing (overall/universal entropy)

Question 7

What does it mean when Entropy (S) is > 0? When S is < 0?

Answer 7

S > 0 (positive number) is favorable; S < 0 (negative) is unfavorable

Question 8

Is binding of a flexible ligand entropically favorable or unfavorable and why?

Answer 8

Unfavorable. A flexible peptide can have many different conformations and the receptor can only accept one conformation. The statistical likelihood for getting the right conformation is low. Also, a bound ligand is locked into one conformation (decr entropy). Even though the local entropy is low, the overall system entropy may still be high.

Question 9

______ determines whether a process/reaction is favorable or will occur spontaneously

Answer 9

Free energy (G)

Question 10

What is the Free energy equation?

Answer 10

G = H - TS

Question 11

What does it mean if Free energy (G) is < 0 or > 0?

Answer 11

G < 0 (negative) means a reaction is favorable, spontaneous and exergonic; G > 0 means a reaction is unfavorable, not spontaneous and endergonic

Question 12

What is G (Free energy) at equilibrium?

Answer 12

Zero

Question 13

What does it mean for reactions be thermodynamically coupled?

Answer 13

The overall G for a series of reactions equals the sum of the G’s of the individual steps; i.e. a thermodynamically unfavorable reaction can be driven by a thermodynamically favorable one

Question 14

What is kinetic energy? How does heat affect kinetic energy?

Answer 14

Molecular motion ; Increased heat = increased motion

Question 15

What kinds of energy do we encounter in biochemical systems?

Answer 15

Kinetic energy and potential energy

Question 16

What is Entropy?

Answer 16

A measure of the randomness or disorder of a system (S); it is a reflection of statistical probability

Question 17

What is Entropy?

Answer 17

A measure of the randomness or disorder of a system (S); it is a reflection of statistical probability

Question 18

Describe the equation for the equilibrium constant (K) and how this relates to reactions.

Answer 18

K = [C][D] / [A][B]
Reactions aren’t all or none and will go back and forth; the concentrations in this expression are at equilibrium not at starting

Question 19

Describe the equation that relates equilibrium constant to free energy equation.

Answer 19

G = G* + RTlnK (G* is the free energy change under standard conditions; R is the gas constant; T is absolute temperature). At equilibrium, G is 0, so the equation is rearranged as such: G* = -RTlnK

Question 20

G* = -RTlnK describes what?

Answer 20

It is the link between equilibrium constant and free energy; it describes the extent of the reaction (not the rate)

Question 21

What does a high equilibrium constant (K) mean?

Answer 21

That G will be more negative and the molecules wants to spend more time in products

Question 22

Describe first order rates of reactions.

Answer 22

A –> P Rate = k1 [A] Rate is proportional to the concentration of A raised to the first power

Question 23

Describe second order rates of reations

Answer 23

A + A –> A2 Rate = k2 [A]^2

A + B –> C + D Rate = k3 [A] [B]

Question 24

Describe psuedo-first order rates of reactions

Answer 24

A + H2O –> X Rate = k4 [A] {H2O]
Water is constant (bc there is so much of it and little is consumed) so equation can be rewritten as first order even though it is second order : Rate = k5 [A]
This applies to situations where concentrations of one of the reactants doesn’t change much during rxn

Question 25

How is rate of reaction related to equilibrium?

Answer 25

``` A + B C + D Rate (forward) = k1 [A] [B] Rate (back) = k-1 [C] [D] At equilibrium there is no net change so forward and back are equal: k1 [A] [B] = k-1 [C] [D] K = [C][D]/[A][B] = k1/k-1 ```

Question 26

What determines the rate constants?

Answer 26

Activation energy (G++)

Question 27

What is activation energy (G++)?

Answer 27

A measure of energy required to excite molecules into a transition state that is capable of progressing into products. The higher the barrier (transition state), the slower the reaction and the more kinetic energy is needed or a catalyst

Question 28

What can lower the transition state?

Answer 28

A catalyst like an enzyme

Question 29

The large difference in ______ between oxygen and hydrogen means that water is a _____ molecule

Answer 29

electronegativity; polar

Question 30

How do the polar interactions of water affect the physical properties compared to CH4, NH3, H2S?

Answer 30

It greatly increases boiling and melting point compared to other liquids because of high hydrogen bonding

Question 31

What are hydrogen bonds?

Answer 31

Noncovalent electrostatic interactions in which the electrons on oxygen interact with a hydrogen on another molecule. These are seen in both solid and liquid water and stabilize water immensely.

Question 32

Besides hydrogen bonds, what are other examples of electrostatic noncovalent bonding?

Answer 32

charge-charge; charge-dipole; dipole-dipole; charge-induced dipole; dispersion

Question 33

Why are weak interactions important?

Answer 33

The sum of the weak interactions stabilizes molecules; contributes to protein folding, DNA shape and transcription

Question 34

The ________ can drive self-assembly in biological systems

Answer 34

hydrophobic effect

Question 35

Describe the hydrophobic effect

Answer 35

nonpolar substances in water can't interact with water and, at an entropic cost, water must surround the nonpolar substance in an ordered fashion (unfavorable). Water is not repelled by nonpolar substance but will form cages around them. Ampipathic molecules will self-assemble into layers or micelles (or proteins must fold to hide nonpolar portions) to increase the entropy of water

Question 36

Molecules that have both polar and nonpolar regions are known as _______

Answer 36

amphipathic

Question 37

Is the hydrophobic effect spontaneous or not spontaneous?

Answer 37

spontaneous

Question 38

What is the Bronsted-Lowry definition of Acid and Base?

Answer 38

Acid is a proton donor and Base is a proton acceptor.

Question 39

Water can dissociate into ____ and ____ ions.

Answer 39

Protons and hydroxyl ions

Question 40

The equilibrium of water dissociation is described by the ______

Answer 40

Product of water (Kw) | Kw = [H+] [OH-] = 1 x 10^-14

Question 41

The concentration of protons is usually expressed as ___

Answer 41

pH | pH = -log [H+]

Question 42

When an acid dissociates, it produces a _____ and a _____.

Answer 42

Proton and an anion (conjugate base)

Question 43

The acid and the corresponding anion (conjugate base) are known as the _________

Answer 43

Conjugate pair

Question 44

Bases join with protons to make a _____.

Answer 44

Conjugate acid.

Question 45

The STRENGTH of an acid (its tendency to give up its proton) is expressed by the ________

Answer 45

Acid dissociation constant (Ka);

Question 46

What is the Ka in a strong acid vs. a weak acid?

Answer 46

Strong acids have high Ka values vs. weak acids have small Ka values

Question 47

What is the equation for the acid dissociation constant (Ka)?

Answer 47

For the acid HA, HA H+ + A- | Ka = [H+] [A-] / [HA]

Question 48

Define pKa

Answer 48

The pH of the solution when the molar concentrations of the acid and its conjugate base are equal. It is the -logKa which is log(1/Ka)

Question 49

What is the purpose of the Henderson-Hasselbach equation and what is the actual equation?

Answer 49

Useful for estimating the pH of a buffer solution and finding the equilibrium pH in an acid-base reaction. The equation is derived from taking the acid dissociation constant equation (Ka) and rearranging it, then taking the logarithms of that equation: pH = pKa + log ([A-]/[HA])

Question 50

Some acids carry __________ which can dissociate sequentially at different pKa.

Answer 50

Multiple protons; The first proton dissociates more readily than the second.

Question 51

What is the pKa for a strong and weak acid (high or low)?

Answer 51

Strong acid (low pKa); Weak acid (high pKa)

Question 52

True or false: water is capable of dissociating

Answer 52

True

Question 53

What is a buffer and when is the buffering capacity at its best.

Answer 53

Buffers are composed of weak acids and their conjugate bases (or weak bases and their conjugate acids) used to make systems less sensitive to the addition of strong acids or bases. They function greatest when they are at the pKa of the acid or base (no more than +/- 1 pH unit away from the pKa value.

Question 54

_______ are the building blocks of proteins.

Answer 54

Amino acids

Question 55

What are some functions of amino acids?

Answer 55

Precursors for biologically important compounds (heme, purines, pyrimidines, neurotransmitters, hormones); utilized as fuel for metabolism

Question 56

What is the general structure of an amino acid

Answer 56

An alpha (central) carbon surrounded by four substituents: Amino group (NH2), Carboxylic acid (COOH), Side chain (R), Hydrogen

Question 57

Since there are four different substituents attached to the alpha carbon, this carbon is _______. This means two different versions of any amino acid are possible. These are called ______ or _____ and are mirror images of one another also called ______

Answer 57

asymmetric; optical isomers or stereoisomers; enantiomers

Question 58

True or false: only D-amino acids are found in proteins.

Answer 58

False; only L-amino acids are found in proteins. D-amino acids are found in nature (bacterial cell walls) but are not incorporated into proteins.

Question 59

How do the 20 amino acids side chains differ and what determines how a protein will fold and function?

Answer 59

Side chains differ in size, polarity and charge. The proteins amino acid sequence determines how it will fold and function.

Question 60

The 20 amino acids based on side chain structure can be classified as _____ or ______

Answer 60

apolar or polar

Question 61

What is a characteristic about the apolar (nonpolar) side chains and name all of the apolar amino acids.

Answer 61

Hydrocarbons; Glycine, Alanine, Valine, Leucine, Isoleucine, Methionine, Phenylalanine, Tryptophan, Proline

Question 62

Which amino acid is achiral? Why?

Answer 62

Glycine; Its side chain is a single hydrogen

Question 63

_____ is an apolar amino acid in which the side chain is covalently linked to the amino group forming a cyclic structure.

Answer 63

Proline

Question 64

Polar amino acids can be subdivided based upon _____ exhibited by their side chains at physiologic pH. The three groups are: ____, ____ and _____.

Answer 64

Charge; neutral, basic, acidic

Question 65

Which amino acids contain hydroxyl groups in their side chains? Why are hydroxyl groups important?

Answer 65

Serine, threonine, tyrosine; They can serve as phosphorylation sites for kinases or attachment points for other modifiers (sugars)

Question 66

What are the polar neutral amino acids?

Answer 66

Serine, Threonine, Tyrosine, Asparagine, Glutamine, Cysteine

Question 67

The side chains of cysteine contains a ______ group that is quite reactive. These groups of two cysteine residues can be oxidized to form a covalent ______.

Answer 67

sulfhydryl (thiol) group; disulfide bond

Question 68

Two covalently bonded cysteines form a species known as ______

Answer 68

Cystine

Question 69

What are the polar basic amino acids? Which are strongly basic and weakly basic

Answer 69

Lysine, Arginine, Histidine Lysine and Arginine are strongly basic. Histidine's side chain contains the weak base imidazole and is close to physiological pH. Small changes in pH will change the histidine side chain's protonation state from uncharged to charged and vice versa.

Question 70

What are the polar acidic amino acids?

Answer 70

aspartate and glutamate; they readily donate protons leaving them with net negative charge as physiological pH. The uncharged forms (protonated) are known as aspartic acid and glutamic acid

Question 71

What is the difference between aspartic acid and asparagine?

Answer 71

They are different amino acids. Aspartic acid contains a carboxylic acid, asparagine contains an amide.

Question 72

What part of the amino acids are peptide bonds formed?

Answer 72

The hydroxyl group on the carboxylic acid covalently bonds to the amino group on another amino acid (condensation reaction; loses H2O)

Question 73

Peptides and pH: what happens when you link amino acids together into a peptide?

Answer 73

You lose the acidic or basic groups (ionizable groups)

Question 74

What is the "net charge" of the peptide?

Answer 74

The SUM of the charge states of ALL ionizable groups

Question 75

What is Isoelectric point (pI)?

Answer 75

The pH value at which all positive and negatively charged groups of a protein are balanced, yielding a net charge of zero.

Question 76

What charge does the protein have if the pH < pI; when the pH > pI?

Answer 76

pH < pI: protein has a net positive charge | pH > pI: protein has a net negative charge

Question 77

How many ionizable groups does an amino acid have?

Answer 77

Two or three. At least two (amino group and carboxylic acid); three if the side chain is ionizable as well

Question 78

What is the pKa for the carboxylic acid group and the amino group? What kind of graph or curve does this create?

Answer 78

carboxylic acid (2-3); amino group (9-10); biphasic titration curve.

Question 79

True or false: the peptide bond is readily ionizable

Answer 79

False; formation of the peptide bond makes it not easily ionizable compared to the separate amino acids

Question 80

When basic groups on amino acids with a pKa of 9-12 are placed into solution of pH 7.5, will the groups be protonated or deprotonated and what will their charge be?

Answer 80

Protonated; positively charged.

Question 81

When acidic groups on amino acids with pKa of 2-4 are placed into a solution of pH 7.5, will the groups be protonated or deprotonated and what will their charge be?

Answer 81

deprotonated; negatively charged

Question 82

Below its pI, a protein will have a net ____ charge, above its pI, a protein carries a net _____ charge.

Answer 82

Positive, negative

Question 83

At its pI value, a protein will typically be at its _______(lowest/highest) solubility in aqueous solution

Answer 83

Lowest (no net charge)