MGD 1-3 Flashcards
Describe the structure of an amino acid
chiral carbon (Ca) attached to H, NH3+. COO-, R
R group determines AA properties
L-isomer in humans (left)
what are polar bonds in AA?
C=O, N-H, S-H
non polar bonds in AA?
C-H, C-S
what types of bonds are intermolecular bonds?
hydrophobic (come together to exclude water)
hydrogen
van der Waals
ionic
what are the different classifications of AA?
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)
What are zwitterions?
a molecule which contains both a positive and negative group, but holds no net charge i.e. AA in neutral state
when does a zwitterion exist?
at a pH equivalent to the isoelectric point (same as it’s pH)
what is pKa?
1/2 dissociation constant
when is a molecule protonated in terms of pH and pKa
pH
When is a molecule deprotonated in terms of pH and pKa
pH > pKa = net negative charge
pH higher than 1/2 dissociation constant (low dissociation constant - H+ don’t come off easily - alkali)
how to you work out pH and or [H+] when you have 1 value and not the other?
pH = -log[H+] [H+] = 10^(-pH)
what is the primary sequence of AA?
1 basic polypeptide chain of AA - peptide bond (covalent)
what is secondary structure of AA?
when the helix forms through hydrogen bonds - right handed (local spatial arrangement)
what is tertiary structure of AA?
3D folding of the polypeptide chain - including ionic bond, ionic, H-bonds, Van der Waals, hydrophobic
what is quaternary structure of AA?
multiple peptide chains - including non-haem groups coming together (3D structure): ionic, covalent (disulphide), H, van der Waals, hydrophobic bonds
what forms the structure of a a-helix?
hydrogen bonding between C=O and N-H groups stabilise the polypeptide into a helical shape
what are helix breakers and formers?
pro and gly break
ala and leu form
what are key facts (numbers) about a-helix?
3.6AA per turn
0.54nm pitch (steepness of helix)
right handed helix
what forms a ß-sheet and how does it differ from a-helix?
hydrogen bonding between C=O and N-H groups give rise to fully extended parallel or anti-parallel sheets
what are key facts about ß-sheet?
R groups alternate above and below chain
0.35nm between amino acids
which rotation are peptide bonds in? why?
in trans formation as it will clash in R formation
what is the isoelectric point (pI) of a protein?
the pH at which there is no overall net charge
what is the importance of amino acids in proteins?
they determine the way in which polypeptide chain folds
the physical characteristics of the protein
what are fibrous proteins? role, shape, type, example?
role: support, shape, protect
long strands / sheets
single type of repeating secondary structure
e.g. collagen
what are globular proteins?
role: catalysis, regulation
compact shape
several types of secondary structure
e.g. haemoglobin
what is the structure of collagen?
triple helical arrangement of collagen chains (left handed)
contains Gly-X-Y repeating structure
hydrogen bonds stabilise interactions between chains
what are collagen fibrils formed from?
covalently cross-linked collagen molecules
what are motifs in globular proteins?
folding PATTERNs containing 1 or more elements of secondary structure
what are domains in globular proteins?
part of a polypeptide chain that fold into a DISTINCT SHAPE
often has a specific functional role
how do polypeptide chain folds - function?
hydrophobic side chains are buried and polar, charged chains are on the surface
what is protein denaturation?
proteins aren’t v stable
disruption of protein structure
caused by breaking of forces that hold proteins together
how can protein be denatured?
heat & pH: changes ionic / H bonds
detergents / organic solvents: disrupts hydrophobic interactions
what do some proteins require to fold?
chaperones to prevent misfolding and forming the wrong shape - holds onto protein whilst it’s folding
what can misfolding of proteins cause? what is an example?
cause disease - amyloidoses
how do amyloid fibres form?
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)
what are the key features of a peptide bond?
rigid, planar, trans orientation
C=O - N-H
what are misfolded proteins called? what happens to misfolded proteins? what does the cell try to do?
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
what does haem consist of?
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
how is the Fe2+ atom bound to the haemoglobin protein?
via histidine residue on other side of ring that oxygen isn’t bound to
(proximal histidine)
structure of myoglobin?
3 alpha helix (75%)
153 AA
histidine linked to Fe2+ covalently (His 93)
which curves do haemoglobin and myoglobin binding have respectively to oxygen?
myoglobin: hyperbolic - bind to 1 oxygen
haemoglobin: sigmoidal - affinity increased with 1st oxygen bound (cooperative binding)
what is the features of haemoglobin structure?
2 polypeptide chains (a2 & ß2 tetramer)
each chain has essential haem prosthetic group
conformation of each polypeptide chain is v similar to myoglobin
what happens to haemoglobin when it binds to oxygen?
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)
what happens in RBC with 2,3-BPG?
moves curve to right - lowers haemoglobin’s affinity for oxygen
how many 2,3-BPG bind per haemoglobin tetramer?
1 per tetramer (so per 4 polypeptide chains)
when does BPG concentration increase?
at high altitudes - so oxygen is released to respiring tissues quickly
what is the Bohr effect? what does it ensure?
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
Carbon monoxide poising - what happens?
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
how does foetal haemoglobin differ from maternal?
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
what is the molecular change which causes sickle cell anaemia?
mutation of Glutamate to Valine in ß globin
sticky hydrophobic pockets formed by Val instead of hydrophilic by glu - allowing deoxygenated HbS to polymerise
what are sickle cells prone to?
more prone to lyse (anaemia) - premature lysis - to spleen - jaundice more rigid (block microvasculature)
what are thalassaemias?
a group of genetic disorders where there is an imbalance between the number of a & ß globin chains
what is ß-thalassaemia
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
what is a-thalassaemias?
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)
