MGD 1-3

Question 1

Describe the structure of an amino acid

Answer 1

chiral carbon (Ca) attached to H, NH3+. COO-, R
R group determines AA properties
L-isomer in humans (left)

Question 2

what are polar bonds in AA?

Answer 2

C=O, N-H, S-H

Question 3

non polar bonds in AA?

Answer 3

C-H, C-S

Question 4

what types of bonds are intermolecular bonds?

Answer 4

hydrophobic (come together to exclude water)
hydrogen
van der Waals
ionic

Question 5

what are the different classifications of AA?

Answer 5

polar, uncharged (anything with additional charge on top of AA)
polar, charged (has OH group - polar)
non-polar AA (mainly C-H bonds attached to AA)

Question 6

What are zwitterions?

Answer 6

a molecule which contains both a positive and negative group, but holds no net charge i.e. AA in neutral state

Question 7

when does a zwitterion exist?

Answer 7

at a pH equivalent to the isoelectric point (same as it’s pH)

Question 8

what is pKa?

Answer 8

1/2 dissociation constant

Question 9

when is a molecule protonated in terms of pH and pKa

Answer 9

pH

Question 10

When is a molecule deprotonated in terms of pH and pKa

Answer 10

pH > pKa = net negative charge

pH higher than 1/2 dissociation constant (low dissociation constant - H+ don’t come off easily - alkali)

Question 11

how to you work out pH and or [H+] when you have 1 value and not the other?

Answer 11

pH = -log[H+]
[H+] = 10^(-pH)

Question 12

what is the primary sequence of AA?

Answer 12

1 basic polypeptide chain of AA - peptide bond (covalent)

Question 13

what is secondary structure of AA?

Answer 13

when the helix forms through hydrogen bonds - right handed (local spatial arrangement)

Question 14

what is tertiary structure of AA?

Answer 14

3D folding of the polypeptide chain - including ionic bond, ionic, H-bonds, Van der Waals, hydrophobic

Question 15

what is quaternary structure of AA?

Answer 15

multiple peptide chains - including non-haem groups coming together (3D structure): ionic, covalent (disulphide), H, van der Waals, hydrophobic bonds

Question 16

what forms the structure of a a-helix?

Answer 16

hydrogen bonding between C=O and N-H groups stabilise the polypeptide into a helical shape

Question 17

what are helix breakers and formers?

Answer 17

pro and gly break

ala and leu form

Question 18

what are key facts (numbers) about a-helix?

Answer 18

3.6AA per turn
0.54nm pitch (steepness of helix)
right handed helix

Question 19

what forms a ß-sheet and how does it differ from a-helix?

Answer 19

hydrogen bonding between C=O and N-H groups give rise to fully extended parallel or anti-parallel sheets

Question 20

what are key facts about ß-sheet?

Answer 20

R groups alternate above and below chain

0.35nm between amino acids

Question 21

which rotation are peptide bonds in? why?

Answer 21

in trans formation as it will clash in R formation

Question 22

what is the isoelectric point (pI) of a protein?

Answer 22

the pH at which there is no overall net charge

Question 23

what is the importance of amino acids in proteins?

Answer 23

they determine the way in which polypeptide chain folds

the physical characteristics of the protein

Question 24

what are fibrous proteins? role, shape, type, example?

Answer 24

role: support, shape, protect
long strands / sheets
single type of repeating secondary structure
e.g. collagen

Question 25

what are globular proteins?

Answer 25

role: catalysis, regulation compact shape several types of secondary structure e.g. haemoglobin

Question 26

what is the structure of collagen?

Answer 26

triple helical arrangement of collagen chains (left handed) contains Gly-X-Y repeating structure hydrogen bonds stabilise interactions between chains

Question 27

what are collagen fibrils formed from?

Answer 27

covalently cross-linked collagen molecules

Question 28

what are motifs in globular proteins?

Answer 28

folding PATTERNs containing 1 or more elements of secondary structure

Question 29

what are domains in globular proteins?

Answer 29

part of a polypeptide chain that fold into a DISTINCT SHAPE | often has a specific functional role

Question 30

how do polypeptide chain folds - function?

Answer 30

hydrophobic side chains are buried and polar, charged chains are on the surface

Question 31

what is protein denaturation?

Answer 31

proteins aren't v stable disruption of protein structure caused by breaking of forces that hold proteins together

Question 32

how can protein be denatured?

Answer 32

heat & pH: changes ionic / H bonds | detergents / organic solvents: disrupts hydrophobic interactions

Question 33

what do some proteins require to fold?

Answer 33

chaperones to prevent misfolding and forming the wrong shape - holds onto protein whilst it's folding

Question 34

what can misfolding of proteins cause? what is an example?

Answer 34

cause disease - amyloidoses

Question 35

how do amyloid fibres form?

Answer 35

amyloid fibres - misfolded, insoluble form of a normally soluble protein highly ordered with lots of ß-sheets core ß-sheet forms before the rest of the protein inter-chain assembly stabilised by hydrophobic interactions between aromatic AA (overtime, more and more of the misfolded protein causes the disease)

Question 36

what are the key features of a peptide bond?

Answer 36

rigid, planar, trans orientation | C=O - N-H

Question 37

what are misfolded proteins called? what happens to misfolded proteins? what does the cell try to do?

Answer 37

prions marked for destruction (ubiquinalation) or they may accumulate intracellularly if misfolding occurs, cell upregulates the chaperone proteins to try and rescue the misfolded proteins

Question 38

what does haem consist of?

Answer 38

a protoporphyrin ring (Fe centre attached to 4 N on the sides) Fe2+ can make 2 additional bonds to oxygen - one on top and one below on plane

Question 39

how is the Fe2+ atom bound to the haemoglobin protein?

Answer 39

via histidine residue on other side of ring that oxygen isn't bound to (proximal histidine)

Question 40

structure of myoglobin?

Answer 40

3 alpha helix (75%) 153 AA histidine linked to Fe2+ covalently (His 93)

Question 41

which curves do haemoglobin and myoglobin binding have respectively to oxygen?

Answer 41

myoglobin: hyperbolic - bind to 1 oxygen haemoglobin: sigmoidal - affinity increased with 1st oxygen bound (cooperative binding)

Question 42

what is the features of haemoglobin structure?

Answer 42

2 polypeptide chains (a2 & ß2 tetramer) each chain has essential haem prosthetic group conformation of each polypeptide chain is v similar to myoglobin

Question 43

what happens to haemoglobin when it binds to oxygen?

Answer 43

undergoes conformational change (rotate 15 degrees due to neg charged group) oxygen binding promotes R state (binds easily, less go less easily - to the left) deoxyhaemoglobin can exist in R or T state (to the right - pick up O2 less easily - 2,3-BPG)

Question 44

what happens in RBC with 2,3-BPG?

Answer 44

moves curve to right - lowers haemoglobin's affinity for oxygen

Question 45

how many 2,3-BPG bind per haemoglobin tetramer?

Answer 45

1 per tetramer (so per 4 polypeptide chains)

Question 46

when does BPG concentration increase?

Answer 46

at high altitudes - so oxygen is released to respiring tissues quickly

Question 47

what is the Bohr effect? what does it ensure?

Answer 47

binding of H+ and CO2 lowers affinity of haemoglobin for oxygen - curve shifts to right metabolically active tissues produce large amounts of H+ and CO2 Bohr effect ensures the delivery of O2 is coupled to demand

Question 48

Carbon monoxide poising - what happens?

Answer 48

CO combines with FERROmyoglobin and FERROhaemoglobin and blocks oxygen transport (binds with higher afifnity, irreversibly) it also changes the affinity of haemoglobin to higher for oxygen - means less readily drop off to tissues

Question 49

how does foetal haemoglobin differ from maternal?

Answer 49

foetal haemoglobin has higher affinity for oxygen than maternal red cells (shift to the left), allows transfer of O2 to foetal blood supply from mother readily picks up oxygen from mother by the time the blood gets round to the foetus, must have higher affinity to pick up O2

Question 50

what is the molecular change which causes sickle cell anaemia?

Answer 50

mutation of Glutamate to Valine in ß globin | sticky hydrophobic pockets formed by Val instead of hydrophilic by glu - allowing deoxygenated HbS to polymerise

Question 51

what are sickle cells prone to?

Answer 51

``` more prone to lyse (anaemia) - premature lysis - to spleen - jaundice more rigid (block microvasculature) ```

Question 52

what are thalassaemias?

Answer 52

a group of genetic disorders where there is an imbalance between the number of a & ß globin chains

Question 53

what is ß-thalassaemia

Answer 53

decreased or absent ß-globin chain production a-chains unable to form stable tetramers - no ß to form with symptoms appear AFTER birth - before birth no ß chains, only a and gamma

Question 54

what is a-thalassaemias?

Answer 54

decreased / abscent a-globin chain production ß-chains CAN form stable tetramers with increased affinity for oxygen onset before birth (excess of ß-chains bind to oxygen more tightly - so doesn't readily release oxygen)