Chapter 1 Flashcards
1
Q
Amino Acid
A
- Have two functional groups: Amino group and carboxyl group
- a-amino acids: amino group and carboxyl group are bonded to same carbon (alpha carbon)
- Alpha carbon also has a Hydron atom attached and a R group (specific to amino acid)
- AAMC focuses on proteinogenic amino acids (20 a- amino acids)
- amphoteric: can accept a proton/donate a proton
- Reaction depends on pH of environment
2
Q
Amino Acid Stereochemistry
A
- In most amino acids, a-carbon is chiral center (four groups attached to it, THEREFORE most amino acids are optically active
- Exception: glycine (hydrogen atom as R group, therefore achiral)
- All chiral amino acids in eukaryotes are L-amino acids (amino group drawn of left in Fischer projection)
- All have absolute configuration (S)
- Exception: cysteine (L-amino acid with R absolute configuration because -CH2SH group takes priority over -COOH group)
3
Q
Amino Acids with Nonpolar, Nonaromatic Side Chains
A
- Glycine
- Alanine
- Valine
- Leucine
- Isoleucine
- Methionine
- Proline
4
Q
Alkyl Side Chains (1 to 4 C)
A
- Glycine
* One H as side chain, therefore achiral - Alanine
- Valine
- Leucine
- Isoleucine
* Has chiral carbon in side chain
1 to 4 has alkyl side chains containing 1 to 4 C
5
Q
Methionine
A
- Contains S atom in side chain
- Sulfar has methyl group attached
- Makes relatively nonpolar
6
Q
Proline
A
- Forms cyclic amino acid
- Amino N becomes part of side chain, forming 5 membered ring
- Ring limits where it can appear in protein and role in secondary structure
7
Q
Uncharged Aromatic Side Chains
A
- Tryptophan
* Double-ring containing N
* largest - Phenylalanine
* Benzyle side chain (Benzene ring plus -CH2 group)
* smallest
* Nonpolar - Tyrosine
* OH group added to phenylalanine
* Polar
8
Q
Polar Side Chains (NOT aromatic)
A
- Serine & Threonine
* OH groups in side chains
* Highly polar
* Threonine has chiral carbon in side chain - Asparagine & Glutamine
* Amide side chains
* Amide N doesn’t gain/lose protons with changes in pH
* Don’t become charged - Cysteine
* Thiol (SH) group in side chain
* S is larger and less electronegative than O, so S-H bond is weaker than O-H bond
* Thiol group is prone to oxidation
9
Q
Negatively Charged (Acidic) Side Chains
A
At pH of 7.4
1. Aspartic Acid (Aspartate)
* Related to Asparagine
2. Glutamic Acid (Glutamate)
* Related to glutamine
Aspartate and Glutamate have carboxylate (COO-) groups in side chains NOT amides
Aspartate and Glutamate are deprotonated form of acids
10
Q
Positively Charged (Basic) Side Chains
A
Side chains with positively charged nitrogen atoms
1. Lysine
* Terminal primary amino group
2. Arginine
* 3 N atoms in side chain
* Positive charge delocalized over all 3 N atoms
3. Histidine
* Aromatic ring (imidazole) with 2 N atoms
* One N is protonated and other isn’t
* Under acidic conditions, second N can be protonated giving side chain + charge
11
Q
Hydrophobic & Hydrophilic Amino Acids
A
- Hydrophobic
* Long alkyl side chains
* Ex: Alanine, isoleucine, leucine, valine, phenylalanine
* Found in interior of protein - Hydrophilic
* Charged side chains (positive and negative)
* Ex: Histidine, arginine, lysine, glutamate, aspartate, glutamine, asparagine
* Found on surface of protein
All others are in the middle and not particularly hydrophobic or hydrophilic
12
Q
Alanine
A
Ala
A
13
Q
Arginine
A
Arg
R
14
Q
Asparagine
A
Asn
N
15
Q
Aspartic Acid
A
Asp
D
16
Q
Cysteine
A
Cys
C
17
Q
Glutamic Acid
A
Glu
E
18
Q
Glutamine
A
Gln
Q
19
Q
Glycine
A
Gly
G
20
Q
Histidine
A
His
H
21
Q
Isoleucine
A
Ile
I
22
Q
Leucine
A
Leu
L
23
Q
Lysine
A
Lys
K
24
Q
Methionine
A
Met
M
25
Phenylalanine
Phe
F
26
Proline
Pro
P
27
Serine
Ser
S
28
Threonine
Thr
T
29
Tryptophan
Trp
W
30
Tyrosine
Tyr
Y
31
Valine
Val
V
32
Amino Acid Behavior
* Ioniable group usually gain protons under **acidic** and lose protons under **basic**
* pKa of group is pH where, usually half of molecules are deprotonated
Protonated version of ionizable group = deprotonated version of ionizable group
* If pH < pKa majority will be protonated
* If pH > pKa majority will be deprotonated
33
Amino Acid pKa
Have at least two groups that can be deprotonated so have two pKas
1. pKa 1: Carboxyl group
* Usually ~ 2
2. pKa 2: Amino group
* Usually ~ 9 - 10
For amino acids with ionizable side will have 3 pKa values
34
Positively Charged under Acidic Conditions
At pH 1: lots of protons
* Below pKa of amino group, so amino group becomes fully protonated THEREFORE + charged
* Below pKa of carboxylic acid group, so COOH is fully protonated THEREFORE neutral
35
Zwitterions at Intermediate (Blood, 7.4) pH
At pH 7.4: above pKa of carboxyl below pKa of amino group
* Carboxyl group will deprotonate becoming COO-
* Amino group will protonate becoming NH3+
**Dipolar Ions/Zwitterions:** Molecule that has both positive and negative charge, overall neutral
36
Negatively Charged under Basic Conditions
At pH 10.5: above pKa of both groups
* Carboxylate group already deprotonated, so remains as COO-
* Amino deprotonates becoming -NH2
37
Isoelectric Point (pI)
pH where a molecule is electrically neutral
* When molecule is neutral titration curve will be vertical
Amino acids with acidic side chains have low pI
Amino acids with basic side chains have high pI
38
pI Acidic Amino Acid
Amino acids with charged side chains
* Ex: Glutamic acid, lysine
* Titration curve has extra step
* First deprotonating: proton from main carboxyl group
* Second deprotonating: side chain carboxyl group
39
pI Basic Amino Acid
Two amino groups one carboxyl group
* Ex: lysine
* Loses carboxyl proton
* Loses proton from main amino group
* Loses proton on amino group in side chain
40
Peptide Bond Formation
Condensation/Dehydration Reaction
* Removal of water molecule
* OR acyl substitution reaction (can occur in all carboxylic acid derivatives)
41
Peptide Bond Resonance
* Due to amide groups delocalizable pi electrons they can exhibit resonance
* Resonance restricts rotation of protein backbone around C-N amide bonds THEREFORE more rigid protein
**Amino Terminus/N-Terminus:** Free amino end
**Carboxy Terminus/C-Terminus:** Free carboxyl end
N-terminus drawn on left and C-terminus drawn on right
42
Peptide Bond Hydrolysis
Break apart amide bond by adding H to amide N and an OH to carbonyl C
* Catalyzed by hydrotic enzymes (trypsin and chymotrypsin)
* Only cleave at certain points in peptide chain (trypsin cleaves at carboxyl end of arginine and lysine, chymotrypsin cleaves at the carboxyl end of penylalanine, tryptophan, and tryosine)
43
Residues
Amino acid subunits that makeup peptides
44
Dipeptides
Two amino acid residues
45
Tripeptides
Three amino acid residues
46
Olgiopeptide
Small peptides with up to 20 residues
47
Polypeptides
Longer chains of greater than 20 residues
48
Peptide Bond
Special amide bond between -COO- group of an amino acid and NH3+ of another amino acid
49
Proteins
Polypeptides that are a few up to thousands of amino acids in length
Four levels of structure:
1. Primary (1˚)
2. Secondary (2˚)
3. Tertiary (3˚)
4. Quaternary (4˚)
50
Primary Structure (1˚)
Linear arrangement of amino acids
* Listed from N-terminus (amino end) to C-terminus (carboxyl end)
* Stabilized by covalent peptide bonds between adjacent amino acids
* Encodes all information needed for folding
* Can be determine via sequencin (easiest way is using DNA tha coded for the protein, also possible from protien)
51
Secondary Structure (2˚)
Local structure of neighboring amino acids
* Result of hydrogen bonding between close amino acids
Two common types:
1. a-helices
2. B-pleated sheets
Stability for these structures comes from formation of intramolecular H bonds between different residues
52
a-Helices
Rodlike structure where a peptide chain coils clockwise
* Stabilized by intramolecular H bonds between carbonyl O and amide H four resides down the chain
* Side chain point away from helix core
* Important in **keratin** (structural protein in skin, hair, and fingernails)
53
B-Pleated Sheets
Peptide chains lie along side each other forming rows/strands
* Parallel or antiparallel
* Held together by intramolecular hydrogen bonds between carbonyl O one one chain and amid H in adjacent chain
* Have pleated sheet to have as many hydrogen bonds as possible
* Side chains point above/below plane
54
Proline
* Rigid cyclic structure
* Rarely found in a-helices except when crossing cell membrane
* Rarely found in B-pleated sheets
* Usually found in **turns** between chains of B-pleated sheet and **kinks** at start of a-helix
55
Tertiary Structure (3˚)
**Secondary structures form first and then hydrophobic interactions and hydrogen bonds cause the protein to collapse into proper 3D structure**
* Determined mainly by hydrophilic/hydrophobic interactions between R groups of amino acids
* Hydrophobic wants to be on interior of protein
* Hydrophilic bonds in polypeptide chain pulled in by hydrophobic residues
* Hydrogen bonds stabilize from inside
* Never found on surface of protein
Subtypes:
1. Hydrophobic interactions
2. Acid-base/salt bridges
3. Disulfide links
56
Disulfide Bonds
Bonds that form when two cysteine molecules become oxidized forming cystine
* Requires loss of two protons and two electrons (oxidation)
57
Denaturation
When a protein loses its tertiary structure thus losing its function
* Occasionally reversible
* Unfolded, can't catalyze reactions
* Usuallly heat (increased kinetic energy enough to overcome hydrophobic interactions) and solutes (disrupting elements of 1˚/2˚/3˚/4˚ structure) caused
58
Entropy
Why hydrophobic residues occupy interior of a protein
* Moving to interior increases entropy by allowing water on the surface to have more possible positions/configurations
* + ∆S makes ∆G < 0
* Stabilizes protein
59
Quaternary Structure (4˚)
Interaction between seperate subunits of a multisubunit protein
* Only exist for proteins with more than one polypeptide chain
* Group of subunits
* Represents function form of protein
* Ex: hemoglobin (4 disgtinct subunit, that can each bind with an 0)
Purpose:
1. More stable
2. Reduce DNA needed to encode
3. Catalytic sites brought closer
4. **induce cooperativity/allosteric effects**
