Proteins & Oxygen Transport

Question 1

Define pH

Answer 1

Measurement of Proton concentration

Question 2

What does pKa show? What does a low pKa mean?

Answer 2

The stronger the tendency of an acid to disassociate, the lower the pKa.

Question 3

When pH > pKa, which form of the amino acid dominates?

Answer 3

Deprotonated

Question 4

What is the isoelectric point?

Answer 4

pI is the point at which the protein has no overall charge

Question 5

Acidic proteins have many positively or negatively charged amino acids?

Answer 5

Negative. Acidic proteins have a low pI

Question 6

What are the differences between globular and fibrous proteins?

Answer 6

Globular- several types of secondary structure

Fibrous- 1 repeating primary structure

Question 7

Which amino acid is a helix former? Which ones are helix breakers?

Answer 7

Helix former = alanine, leucine (small, hydrophobic residues)
Helix breaker = proline/glycine (rotation impossible around bond/tiny R group supports other conformations)

Question 8

Describe myoglobin structure

Answer 8

-single subunit with 1 haem group

Question 9

Describe haemoglobin structure

Answer 9

• tetra metric
• 2 alpha/ 2 beta
• 4 haem groups
• Each subunit like a myoglobin molecule

Question 10

Describe differences in haemoglobin and myoglobin binding

Answer 10

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

Question 11

Describe the effects of 2,3-biphosphoglycerate on haemoglobin. Where is 2,3-bpg released in the body?

Answer 11

• oxygen affinity lowered, curve shifts right

- metabolically active tissue which promotes oxygen release and carbon dioxide uptake (for release)

Question 12

What is the inheritance pattern for sickle cell anaemia?

Answer 12

Autosomal recessive, 25% chance of inheriting from two carriers

Question 13

What is the mutation that causes sickle cell anaemia?

Answer 13

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.

Question 14

What is a sickle cell crisis? How does it happen?

Answer 14

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

Question 15

What are thalassemias?

Answer 15

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

Question 16

What are the essential amino acids?

Answer 16

Isoleucine, Leucine, Threonine, Lysine, Methionine, Phenylalanine, Tryptophan, Valine, Histidine

Question 17

What are the four levels of protein structure?

Answer 17

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

Question 18

What is protein denaturation?

Answer 18

disruption of protein structure due to breaking of forces by heat or pH, or organic solvents which disrupt hydrophobic interactions

Question 19

How do proteins fold?

Answer 19

Ordered folding driven by need to find most stable conformation at each step

Question 20

What are amyloidosis?

Answer 20

abnormal protein structures that can cause cell death

Question 21

How does oxygen binding change haemoglobin structure?

Answer 21

oxygen binding promotes the exposure of more haem groups

Question 22

What mediates the change of structure of myoglobin and haemoglobin on binding oxygen?

Answer 22

Fe atom lies outside plane of the ring until oxygen binding. Histidine residue movies in response to this which modifies the structure

Question 23

What is the Bohr effect?

Answer 23

Metabolically active tissue releases H+ and C02 which lowers oxygen affinity. It ensures demand is coupled with supply.

Question 24

How does carbon monoxide affect oxygen binding?

Answer 24

combined with ferromyoglobin and ferrohaemoglobin with high affinity to block oxygen transport, it also acts to increase oxygen affinity for remaining subunits