Midterm Flashcards
(150 cards)
1
Q
Define: biochemistry
A
The study of life at the molecular level
2
Q
Characteristics of living things:
A
Chemical complexity and microscopic organization, systems for using energy, defined functions and regulated interactions between components of the organism, responding to environment, self-replication and -assembly, evolution
3
Q
Biochem is __ not __ life exists.
A
how, why
4
Q
Fundamental features of cells:
A
Plasma membrane, cytoplasm, nucleic acid
5
Q
How big are prokaryotic cells?
A
~1 micrometer in diameter
6
Q
How big are eukaryotic cells?
A
~100 micrometers in diameter
7
Q
What percent of macromolecules are which?
A
15% protein
7% nucleic acid
3% polysaccharides
2% lipids
8
Q
In vivo vs in vitro:
A
In vivo is reductionist and success does not translate to in vitro.
In vitro success in a mouse does not translate to success in a human.
9
Q
Chemical foundations of life - what %?
A
CHONPS - 97%
10
Q
Bulk elements (structural):
A
CHONPS Cl Na Ca K
11
Q
Trace elements (co-factors):
A
Mg, V-Zn, Se, Mo, I
12
Q
Define: configuration
A
Flexible spatial arrangement of atoms within a molecule - can be changed without breaking bonds
13
Q
Define: conformation
A
Fixed spatial arrangement of atoms within a molecule - cannot be changed without breaking bonds
14
Q
Geometric isomer:
A
Same formula but different arrangement of groups with respect to a double bond (can’t rotate)
15
Q
Define: stereoisomers
A
Non-superimposable molecules that differ in configuration at a chiral centre.
Ex: shaking hands - they look the same but interact with others differently
16
Q
Enantiomer vs diasteromer
A
Mirror images; not.
17
Q
How many stereoisomers can be made about n chiral centres?
A
2^n
18
Q
First law of therm:
A
Energy cannot be created or destroyed or whatever
19
Q
Gibbs free energy:
A
Enthalpy (number and kinds of bonds), entropy (randomness); G = H - TS
20
Q
Endergonic vs exergonic:
A
Ender - nonspon, positive delta G
Exer - spon, negative delta G
21
Q
Energy-coupling:
A
Coupling endergonic reactions with exergonic ones can drive thermodynamically unfavourable reactions, giving overall exergonic reactions
22
Q
ATP and metabolism:
A
Anabolic: ATP to ADP
Catabolic: ADP to ATP
23
Q
Cost to fuel body:
A
150 pound person consumes 2800 Calories/day; 50% efficiency so 1400 Calories of ATP; 65 kg of ATP; $10/gram
24
Q
Perpetuation of biology requires that genetic information be:
A
Stably stored, expressed accurately in gene products, reproduce accurately
DNA is v stable because it’s missing a something group
25
How DNA encodes proteins:
Nucleotide sequence -> mRNA -> AAs sequence -> structure of protein -> biological function of protein
26
Water's passive role in biological systems:
Structures of biomolecules are formed in response to interaction with water
27
Water's active role in biological systems:
Participant in many biochemical reactions
28
Define: hydrogen bond
An electrostatic non-covalent interaction between an electronegative atom with a hydrogen linked to it and another electronegative atom with a free electron pair
29
How does a hydrogen bond compare to a covalent bond?
Twice as long, 5% as strong
30
Strength of hydrogen bonds:
Depends on geometry - a straight one is stronger than a bent one
31
Unusual properties of water:
High internal cohesion, heat of vap, specific heat capacity, melting/boiling points; the low density of ice
32
Biological significance of the high specific heat capacity of water:
Most animals are isothermic (need to regulate and maintain temp)
Metabolic processes give off heat
33
Reasons water rocks at hydrogen bonding:
Can be an acceptor or a donor; it's little for optimal positioning
34
Hydrophobic effect:
Water excludes nonpolar substances, and nonpolar substances group together to interact with each other rather than with water
35
Micelle structure (and example):
Shape: Hydrocarbon tails are in the middle with a shell of heads surrounding them in a sphere.
Soap functions like this, allowing greases to come hang out in these hydrophobic centres.
36
Amphipathic molecules:
Contain both hydrophobic and hydrophilic portions (ex: fatty acids)
37
Solubility:
Depends on ratio of polar to nonpolar groups - the larger the nonpolar portion, the less soluble
38
Effects of weak interactions:
Formation and stabilization of structures, recognition interactions of one biomolecule with another, and binding of reactants to enzymes - PASSIVE
39
Important non-covalent interactions:
Hydrogen bonding; ionic, hydrophobic, van der Waals interactions - ACTIVE
40
Hydrogen bonding in nucleotides:
A and T form two; C and G form three
41
Hydrogen bonds and formation of biomolecules:
Not a force for the formation of structures but determinants of specificity
42
Ionic interactions vs water:
Contribution to biomolecular structures is reduced by shielding from water molecules
43
Van der Waals interactions:
Electron clouds of two uncharged atoms interacting
Abundant in core of proteins due to close packing
When two atoms are separated by the sum of their van der Waals radii, attraction is greatest
44
Ionization of water:
```
Keq = [H+][OH-]/[H2O] = 1.8*10^-16M
[H2O] = 55.5 M, constant
```
45
Titration curves of weak acids: *
When pH = pKa, [A-] = [HA]
46
Buffering region: *
When solution is best able to resist changes in pH. Extends one pH unit to either side of the pKa. On a graph, midpoint of the buffer region is pKa.
47
Protonated vs unprotonated:
pH > pKa, unprotonated.
| pH
48
Ideal buffer:
pKa matches the pH you want
49
Henderson-Hasselbalch:
Describes the relationship between pH of solution, pKa of weak acid, and the relative concentrations of the weak acid and conjugate base.
pH = pKa + log ( [A-] / [HA] )
50
Physiological pH:
pH = 7.4
| Changes of 0.05 pH are dangerous (alkalosis, acidosis)
51
Triprotics:
Life Always Has A Goal plus Cysteine and Tyrosine
| Lysine, arginine, histidine, aspartate, glutamate, cysteine, tyrosine
52
When does a polypeptide become a protein? Why?
51 AAs. It was decided that insulin was the shortest protein, and it has 51 AAs.
53
AAs are "bifunctional" which means hecking what?
Have acid and amino groups
54
Stereoisomers of AAs:
All AAs except for glycine have chiral carbons (enantiomers). Typically only L stereoisomers are found in proteins.
55
All AAs have:
Carboxyl group, amino group, alpha carbon, R group
56
Phosphorylation of AAs:
Take an AA that has a hydroxyl group. Add a phosphoryl group by kinase or remove it by phosphatase. Modifies behaviour in a de/activate kind of way.
57
Zwitterion:
The dipolar ion of an AA (ionized in aq)
58
Lecture 8, 42 minutes – exam question????? Fuck
check this out i guess
59
Peptide bonds:
Condensation reactions between carboxyl and amino groups - usually dehydration
60
Orientation of R groups around peptide bonds:
R groups tend to be in trans config
61
How are peptide chains numbered?
From N (amino) to C (carboxyl) termini
62
I literally have no idea what this sentence means
Formation of peptide bonds eliminates the ionisable alpha-carboxyl and alpha-amino groups of the free amino acids
63
Host Defence Peptides:
Naturally occurring antibiotics that can be used as treatment (adaptive immune system) AND as signalling molecules in the innate immune system -- EXPENSIVE
64
Retro-inverse peptides:
Isomers of natural peptides in which the sequence is reversed and D-AAs are used; they keep the topology of the regular peptide but are more resistant to proteolytic degradation. They usually work better than just D-isomers.
65
yeah this makes sense i guess
Reverse (321 rather than 123) and change chiral conformation so that the peptide residues are in the right place, but the carbonyl and amino groups are in different places and it uses D-AAs, so it’s harder to break down
66
How many unique proteins do bacteria/fruit flies/humans have?
5k, 16k, 25k
67
Protein size:
Typically 100-1000 AAs - insulin is shortest with 51, titin is longest with 34 350
68
Estimate protein size:
Divide molecular weight of the protein by 110 (the average weight of an AA)
69
The three-dimensional (secondary/tertiary) structure of proteins is determined by...?
AA sequence
70
The most important forces stabilizing the specific structures of proteins are...?
Non-covalent
71
Protein folding:
Rapid step-wise process. Some can fold into the native conformation without help; some need chaperone/heatshock proteins. Driven by hydrophobic interactions etc.
72
Chaperone proteins:
Help the protein adapt to gradual changes in temperature or other stressors.
73
What does it mean that protein folding is a cooperative process?
If it starts to fold, the whole thing folds. If it starts to fall apart, the whole thing falls apart.
74
Primary structure:
Main chain has NCCNCC pattern with side groups coming off
75
Rules of secondary structure:
Optimize hydrogen bonding potential of main-chain carbonyl and amide groups; represent a favoured conformation
76
Configuration of secondary structure:
Rotation around the C-N bond is restricted due to its partial double-bond nature. Side chains are in trans (except for PRO). Oxygen of carbonyl and hydrogen of amine nitrogen are trans to each other
77
Conformation of secondary structure:
Each alpha-carbon is held in the chain by single bonds, about which there is complete freedom of rotation.
78
Phi and psi angles: *
```
Phi = C-alpha-N
Psi = C-alpha C
```
79
Ramachandran plots:
Show every possible combination of phi and psi angles and highlights actually observed combinations.
80
Steric interference (secondary structures):
Where the polypeptide is running into itself
81
Alpha-helix:
Right-handed helix with 3.6 residues per turn. Each C=O (residue #n) forms a hydrogen bond with the amide hydrogen of residue #n+4. The bonds are almost parallel, which stabilizes the protein.
82
AAs that like helical structures:
MALEK (methionine, alanine, leucine, glutamate, lysine)
83
Tell me something about the phi and psi angles of each residue in an alpha-helix.
They're all pretty similar I guess.
84
AA sequence affects helix stability.
No proline or glycine.
No stretches of similarly charged AAs to minimize repulsion.
Positives and negatives are often 3-4 away from each other in the primary structure so they can be close in the secondary structure.
Aromatics are often 3-4 away to enable hydrophobic interactions.
85
Tell me some things about the dipoles of alpha helices.
Result of C=O groups pointing toward C-terminus; +N, -C. Stabilized by putting an oppositely charged AA at each end (negative at the N terminus, positive at the C).
86
Tell me something about the amphipathic nature of alpha helices.
By placing hydrophobic/philic AAs 3-4 residues apart, you can create a helix with one face all philic and the other face all phobic.
87
Beta sheets and strands:
Almost fully extended polypeptides arranged side by side. Side groups alternately stick out above/below the plane of the sheet.
88
Pauling was the coolest.
Concur.
89
Amphipathic beta sheets:
The whole sheet may be amphipathic, with hydrophobic side chains on one face and hydrophilic side chains on the other.
90
Hydrogen bonds stabilize beta strands.
Bonding between C=O and -NH on adjacent strands.
91
Parallel vs anti-parallel beta strands:
Anti-parallel - strands run in opposite N to C direction. This is more stable due to better hydrogen bonding geometry. A beta sheet can be a mix of parallel and anti-parallel.
92
How are the subunits of quaternary structure held together?
Non-covalent interactions. As per usual?
93
Advantages of quaternary structures:
Stabilizes subunits and prolongs protein life.
Unique active sites are produced at the interface between subunits.
Helps facilitate unique and dynamic combinations of structure/function through physiological changes in tertiary and quaternary structures.
Conserving functional subunits is more efficient than selecting new proteins with ideal functions.
94
What's keratin part of?
Hair and fingernails.
95
Primary structure of keratin:
Pseudo-seven repeat. A and D are hydrophobic.
96
Secondary/tertiary structure of keratin:
Right-handed, amphipathic alpha-helices. A and D residues form a hydrophobic strip.
(Secondary and tertiary are the same I guess.)
97
Quaternary structure of keratin:
Two hydrophobic strips put together to form a coiled-coil, two right-handed helices wrapping around each other in a left-handed fashion.
98
Disulfide bonding in keratin:
Individual units are linked together by cysteine's disulfide bonds. The more bonds there are, the stronger the substance will be (horn vs hair).
99
What's collagen part of?
Tendons, skin, holding the vascular system together. 25% of proteins in the body.
100
Primary structure of collagen:
Gly-X-Y where X is usually proline and Y is usually hydroxyproline, a post-translational modification of proline.
101
Secondary structure of collagen:
Left-handed helices of 3 residues per turn.
102
Tertiary structure of collagen:
The whole thing is a helix okay just accept it
103
Quaternary structure of collagen:
Coiled-coils with three left-handed helices wrapping around each other in a right-handed fashion
104
Strength of collagen comes from...?
Successive linking of individual units into higher order structures. Post-translational modifications (hydroxyproline, hydroxylysine) provide covalent linkages.
105
Collagen and age:
More cross links occur with age, resulting in brittle skin and tougher meat
106
Collagen and post-translational modifications:
The enzymes that perform these reactions require vit C to function. Scurvy happens.
107
Symptoms of scurvy:
Bruising, tooth loss, poor wound healing, bone pain, eventual heart failure.
Milder symptoms include fatigue, irritability, susceptibility to respiratory infections
108
Vit C deficiency: (not scurvy though we already talked about that)
Vit C deficiency leads to defective triple helix (skin lesions, fragile blood vessels, bleeding gums)
109
Genetic diseases involving collagen:
Osteogensis imperfecta, Marfan’s syndrome (Paganini violinist), Stickler syndrome, Ehlers-Danlos syndrome
Associated with brittle and abnormal bone structure, weakened cardiovascular capabilities, abnormal facial features, loose skin/joints, hyperflexibility
110
Primary structure of silk:
Six-residue repeat that is rich in small AAs.
| GSGAGA)(GSGAGA
111
Secondary structure of silk:
Composed primarily of beta-sheets. The extendedness gives strength; the hydrogen bonds between strands and the van der Waals between sheets give flexibility.
112
Uses of genetically engineered silk:
Sutures, artificial ligaments, body armour
113
Where do prion diseases hang out?
Tend to be localized in brain and spinal cord.
114
TSEs:
Transmissible spongiform encephalopathies - proteins misfolding into a pathological, infectious conformation. Progressive and fatal neurodegenerative diseases.
Ex: mad cow, chronic wasting, kuru.
115
PRPCs:
Proteins involved in memory formation. Can misfold into PRPSC, which is pathological (kills neurons) and infectious.
116
Prions are super stable.
They can survive in dirt for decades.
117
Define: ligand
A molecule that is reversibly bound by a protein
118
Ligands and binding sites are complimentary in:
Size, shape, charge, hydrophobicity, electronegativity, hydrogen bonding tendency
119
Myoglobin:
Monomeric protein that facilitates oxygen storage in peripheral tissue. Consists of a polypeptide of 153 residues arranged in eight alpha-helices, and a heme prosthetic group.
120
Hemoglobin:
Tetrameric protein found in erythrocytes that transports oxygen from the lungs to the periphery
121
Heme:
A photopophryn ring system bound to a single Fe2+ atom, to use its oxygen affinity in a controlled way (no free radicals pls).
122
Fe2+ vs Fe3+
2+ binds reversibly; 3+ does not.
123
Heme's interaction with Fe2+:
The ring provides four coordinating interactions with the iron. N acts as an electron donor to stop Fe2+ from becoming Fe3+.
124
Fe2+ needs six coordinating interactions.
Four from heme, one from a histidine imidazole group, and one for oxygen. A distal histidine stabilizes the bound oxygen.
125
How are heme groups bound to Mb or Hb?
In a specific and discrete pocket
126
Oxygen-saturation curve of myoglobin:
Hyperbolic, indicating a single O2 binding constant.
127
P50:
The amount of O2 required to half saturate the protein.
128
P50 of myoglobin:
0.26 kPa - pretty low
129
PO2 of lungs vs of periphery:
13.5 kPa in lungs and 4.0 kPa in periphery. (Myoglobin has a high affinity for O2 so it can grab it even when the PO2 is low.)
130
The fraction of myoglobin saturated with oxygen at a given partial pressure of oxygen:
(theta) = [pO2] / ([pO2] + [P50])
131
Oxygen's positive cooperativity:
The first O2 causes a conformational change that makes it easier to bind subsequent O2. O2 promotes and stabilizes the R state of hemoglobin, which has higher oxygen affinity.
132
A reaction equation concerning R and T states:
Deoxy-T + O2 oxy-R
133
Define: allosteric
"Other site" - allosteric modulators/effectors bind to allosteric proteins at sites separate from the functional binding site.
134
Homotropic vs heterotropic modulators:
Homo: when the modulator and normal ligand are the same.
Hetero: when the modulator is different from the normal ligand.
135
Allosteric activators/inhibitors:
Activators stabilize R state; inhibitors stabilize T state.
136
Structural/functional changes when Hb binds O2:
Iron atom moves into the plane of the ring, making it R state and causing massive changes in the quaternary structure.
137
Flat vs puckered cells:
Deoxygenated is flat; oxygenated is puckered.
138
Oxygen-binding curve of hemoglobin:
In the high PO2 of the lungs, Hb will completely saturate. In the periphery, Hb will release about half of its O2. It is most likely to give up O2 where PO2 is low and that body part needs it.
139
P50 of oxygen closely matches ... ?
Peripheral PO2
140
Oxygen and 2,3-BPG: allosterics
O2 is a homotropic allosteric activator. BPG is a heterotropic allosteric inhibitor.
141
BPG's role in hemoglobin function:
Decreases Hb's affinity for oxygen. Makes basketball stay away for longer.
142
Structure of BPG:
Carries five units of negative charge and binds to the positively charged pocket that is formed at the interface between the subunits of deoxyHb
143
How fetuses breathe:
Foetal Hb has one less unit of positive charge (AA) than adult Hb because it has to steal O2 from the mother’s blood. By having a less positive charge, it is less likely to bond with BPG, giving it a higher affinity for Hb.
144
BPG and high-altitude adaptation:
BPG increases (from 5 to 8 mM), lowering O2 affinity to ensure delivery to periphery.
145
Bohr effect:
pH dependence of hemoglobin's oxygen affinity - at lower pHs, affinity decreases. Active tissues have lower pHs, so Hb releases more oxygen there. During extreme exercise, muscles may produce lactic acid to further drop the pH.
146
Coordination of O2 delivery and CO2 removal - mechanism 1:
CO2 is taken up into red blood cells and converted to bicarbonate and a proton by the enzyme carbonic anhydrase.
CO2 + H2O ←→ H+ + HCO3
While CO2 is being taken up, the Bohr effect releases more O2.
147
Coordination of O2 delivery and CO2 removal - mechanism 2:
CO2 can form a covalent carbamate linkage to the N terminus of each chain of a hemoglobin chain to form carbaminohemoglobin.
Carbamino hemoglobin has a lower O2 affinity than Hb. Bohr effect releases more O2.
148
Sickle-cell anemia:
Results from a single amino acid change (Glu6Val – sixth spot turns from a glutamate to valine). Hydrophilic residue replaced with a hydrophobic. Fibres form at low PO2, blocking blood flow to the extremities.
149
How does SCA affect R/T states?
T state hemoglobin is rigid; R state is aight, still flexy
150
Malaria and SCA:
Malaria infects red blood cells and decreases their pH. The lower pH will cause the cell to dump its O2 and sickle. The malarial cells will be identified as sickled and will be destroyed by the spleen.
