CGIER 37 - Haemoproteins III: Molecular diseases and mutant haemoglobins

Question 1

desferal functional group

Answer 1

hydroxylic acid

Question 2

2 major functions of haemoglobin

Answer 2

transport of oxygen to tissues

transport of CO2 and protons away from tissues

Question 3

carbamate

Answer 3

when CO2 combines with amino acid residue in globin chain of haemoglin it DOES NOT compete with O2

Question 4

haemoglobin variants

Answer 4

HbA Adult a2β2
HbF Foetal a2γ2 (alpha2 gamma2)
HbA2 Minor adult form a2δ2 (alpha2 delta 2)
HbS Sickle-cell anaemia a2 βS2

Question 5

where are alpha globin genes located on human chromosomes

Answer 5

chromosome 16

2 gene copies per chromosomes

Question 6

where are beta globin genes on human chromosome

Answer 6

chromosome 11

1 gene copy per chromosome

Question 7

what does P50 value measure

Answer 7

measures strength of binding to oxygen

the pO2 at which % saturation is 50%

Question 8

Mb P50

Answer 8

1 Torr

Question 9

Why is foetal haemoglobin different to adult haemoglobin

Answer 9

Gets O2 from mother and not environment directly

Must have a higher affinity for oxygen than adult as it must receive O2 from mother’s blood

Question 10

HbA: P50

Answer 10

26.8 Torr in normal red blood cells

Question 11

HbF P50

Answer 11

19 Torr

Question 12

what causes mutant haemoglobins

Answer 12

change in DNA base sequence of one of the globin genes
change in amino acid sequence of globin
change in protein structure and function -> an inherited disease

Question 13

classification of globin defects

Answer 13

HAEMOGLOBINOPATHIES

THALASSAEMIAS

Question 14

HAEMOGLOBINOPATHIES

Answer 14

Normal amounts of defective globin subunits (qualitative defects)

Question 15

THALASSAEMIAS

Answer 15

Abnormal amounts of normal globin subunits

quantitative defects

Question 16

haemoglobinopathy - hameoglobin M

Answer 16

The proximal Histidine residue is replaced by Tyrosine in either the α or β subunit
In the presence of O2 and proximal tyrosine oxidation of the haem iron from the +II (ferrous) to the +III (ferric) state occurs
Result: As iron(III) cannot bind O2 transport of O2 is impaired.

Question 17

Haemoglobinopathy - Haemoglobin S

Answer 17

An amino acid substitution occurs on the exterior of the β globin subunit
Glutamate CH2CH2COO- is replaced by Valine
- CH(CH3)2
In deoxyhaemoglobin S, Valine is exposed on the
surface of the molecule and creates a ‘sticky patch’
HbS molecules can aggregate to form insoluble fibres within the erythrocyte
The erythrocytes deform into ‘sickle cells’
Sickle cells get stuck in small capillary beds
Polar to hydrophobic interactions
superpolymer
precipitates out

Question 18

short term consequences of haemoglobin S

Answer 18

Bone pain due to sickle cells stuck in capillary beds

Question 19

long term consequences of haemoglobin S

Answer 19

Chronic anaemia due to destruction of erythrocytes 
Organ damage (kidneys, heart & lungs) 
Cerebrovascular accidents

Question 20

diagnosis of haemoglobin. S

Answer 20

Protein or DNA analysis

Question 21

Haemoglobin S treatment

Answer 21

Repeated blood transfusion

Question 22

a thalassaemia

Answer 22

has too little a globin chains

Question 23

β thalassaemia

Answer 23

has too little β globin chains

Question 24

causes of thalassaemia

Answer 24

Thalassemia is a disorder caused by the weakening and destruction of red blood cells.
Thalassemia is caused by variant or missing genes that affect how the body makes hemoglobin

Question 25

is thalassaemia quantitative or qualitative

Answer 25

quantitative

Question 26

where is thalassaemia common in the world

Answer 26

Common in Mediterranean areas, parts of Africa and South East Asia

Question 27

what does each Hb subunit contain

Answer 27

Each protein subunit contains a haem prosthetic group Fe(II)- protoporphyrin IX