Proteins & Oxygen Transport Flashcards
Define pH
Measurement of Proton concentration
What does pKa show? What does a low pKa mean?
The stronger the tendency of an acid to disassociate, the lower the pKa.
When pH > pKa, which form of the amino acid dominates?
Deprotonated
What is the isoelectric point?
pI is the point at which the protein has no overall charge
Acidic proteins have many positively or negatively charged amino acids?
Negative. Acidic proteins have a low pI
What are the differences between globular and fibrous proteins?
Globular- several types of secondary structure
Fibrous- 1 repeating primary structure
Which amino acid is a helix former? Which ones are helix breakers?
Helix former = alanine, leucine (small, hydrophobic residues)
Helix breaker = proline/glycine (rotation impossible around bond/tiny R group supports other conformations)
Describe myoglobin structure
-single subunit with 1 haem group
Describe haemoglobin structure
- tetra metric
- 2 alpha/ 2 beta
- 4 haem groups
- Each subunit like a myoglobin molecule
Describe differences in haemoglobin and myoglobin binding
Myoglobin- hyperbolic binding, high affinity, oxygen released when partial pressure low
Haemoglobin- sigmoidal binding curve, cooperative binding, binding of oxygen promotes stable high affinity R-state
Describe the effects of 2,3-biphosphoglycerate on haemoglobin. Where is 2,3-bpg released in the body?
- oxygen affinity lowered, curve shifts right
- metabolically active tissue which promotes oxygen release and carbon dioxide uptake (for release)
What is the inheritance pattern for sickle cell anaemia?
Autosomal recessive, 25% chance of inheriting from two carriers
What is the mutation that causes sickle cell anaemia?
Hydrophilic glutamate substituted for hydrophobic valine. Hydrophobic pocket formed that causes haemoglobin to polymerise and distort red blood cell shape. Causes premature death, 30 days.
What is a sickle cell crisis? How does it happen?
In tense state, terminal valine exposed. Red blood cells polymerise. They can’t get through microvasculature due to lower flexibility and size. Causes ischemia, pain, necrosis and often organ damage
What are thalassemias?
Imbalance in beta and alpha subunits.
Beta subunit deficiency- alpha chains unable to form stable tetramers. Symptoms appear after birth because the predominant hemoglobin at birth is still fetal hemoglobin (HbF). HbF has two alpha chains (like Hb A) and two gamma chains (unlike Hb A). It has no beta chains so the baby is protected
Alpha subunit deficiency- severity depends on the extent of mutation (several genes for alpha subunits). Beta sheets can form stable tetramers with increased affinity for oxygen. Symptoms appear before birth
What are the essential amino acids?
Isoleucine, Leucine, Threonine, Lysine, Methionine, Phenylalanine, Tryptophan, Valine, Histidine
What are the four levels of protein structure?
Primary- linear amino acid sequence
Secondary- local spatial arrangement of polypeptide backbone (alpha helixes and beta sheets)
Tertiary- The overall 3D configuration of the protein
Quaternary- association between different polypeptides
What is protein denaturation?
disruption of protein structure due to breaking of forces by heat or pH, or organic solvents which disrupt hydrophobic interactions
How do proteins fold?
Ordered folding driven by need to find most stable conformation at each step
What are amyloidosis?
abnormal protein structures that can cause cell death
How does oxygen binding change haemoglobin structure?
oxygen binding promotes the exposure of more haem groups
What mediates the change of structure of myoglobin and haemoglobin on binding oxygen?
Fe atom lies outside plane of the ring until oxygen binding. Histidine residue movies in response to this which modifies the structure
What is the Bohr effect?
Metabolically active tissue releases H+ and C02 which lowers oxygen affinity. It ensures demand is coupled with supply.
How does carbon monoxide affect oxygen binding?
combined with ferromyoglobin and ferrohaemoglobin with high affinity to block oxygen transport, it also acts to increase oxygen affinity for remaining subunits
