haemoglobin

Question 1

primary function of red blood cells

Answer 1

carry oxygen from lungs to tissues

Question 2

other function of red blood cells

Answer 2

transfer CO2 from tissues to lungs

Question 3

3 features of mature red cells

Answer 3

no nucleus, no mitochondria, contains haemoglobin (exclusive; if free in plasma has oxidative properties -> toxic)

Question 4

when does haemoglobin synthesis occur

Answer 4

during development of red blood cells before extrude nucleus, beginning in pro-erythroblast: 65% erythroblast stage, 35% reticulocyte stage

Question 5

structure of haemoglobin, and where these are synthesised

Answer 5

consists of 4 haem groups (synthesised in mitochondria) and 4 globin chains (synthesised in ribosomes)

Question 6

how is iron transported into the cell for haem

Answer 6

iron binds to transferrin -> transferrin iron complex endocytosed through vesicles, then transported to mitochondria -> transferrin released

Question 7

what other proteins is haem present in

Answer 7

myoglobin, cytochromes, peroxidases, catalases, tryptophan

Question 8

what is haem a combination of

Answer 8

protoporphyrin ring with central iron atom (ferroprotoporphyrin)

Question 9

what form is iron usually in in haem, and significance

Answer 9

ferrous form (Fe2+), combine reversibly with O2

Question 10

where is haem mainly synthesised and by which enzyme; significance of stage

Answer 10

mitochondria, which contain enzyme ALAS; d-ALA negative feedback so regulatory step

Question 11

how many functional globin chains, and the 2 clusters

Answer 11

8, arranged in B- and a-clusters

Question 12

what globin genes are present in B-cluster, and where are they (location on chromosome)

Answer 12

b, g, d and e globin genes on short arm of chromosome 11

Question 13

what globin genes are present in a-cluster, and where are they (location on chromosome)

Answer 13

a and z globin genes on short arm of chromosome 16

Question 14

globin gene clusters: chromosome 16 embryo

Answer 14

Gower 1 and 2, Portland

Question 15

globin gene clusters: chromosome 11 foetus

Answer 15

HbF

Question 16

globin gene clusters: chromosome 11 adult

Answer 16

HbF, HbA2, HbA

Question 17

globin gene expression and switching: when are z-, a-, y- and B-globin chains synthesised, and significance on disorders

Answer 17

z-globin chains first to be produced in embryogenesis, but stop early on after 6-7 weeks of gestation; a-globin chains takes over as predominant chain in foetal and adult life; if defect in a-globin chain production, affects embryo very early on in development, causing in-utero death; y-globin chains form foetal Hb so during embryonic development and foetal life, produces these chains for 3-6 months; B-globin chains produced during embryonic development but not in large quantities until after birth; if disorder with B-globin chains, will present later on as still producing y-chains for HbF

Question 18

3 haemoglobins present in normal adults

Answer 18

HbA, HbA2, HbF

Question 19

normal adult haemoglobins: structure and % of HbA

Answer 19

a2B2, 96-98%

Question 20

normal adult haemoglobins: structure and % of HbA2

Answer 20

a2d2, 1.5-3.2%

Question 21

normal adult haemoglobins: structure and % of HbF

Answer 21

a2y2, 0.5-0.8%

Question 22

Hb glycated fraction on HPLC chromatagram

Answer 22

different peaks for different Hb variant masses; HbA peak highest, with HbA2 on right and HbF on left

Question 23

primary globin structure

Answer 23

a 141 AA; non-a 146 AA

Question 24

secondary globin structure

Answer 24

75% a and B chains - helical arrangement

Question 25

tertiary globin structure

Answer 25

approximate sphere, hydrophilic surface (charged polar side chains), hydrophobic core, haem pocket

Question 26

oxyhaemoglobin vs deoxyhaemoglobin

Answer 26

in deoxyhaemoglobin, 2,3-DPG allows binding to haem pocket; more on this and slide 15