Hb

Question 1

Where is Hb found

Answer 1

Only in rbc

Question 2

2 functions of Hb

Answer 2

1. Transports O2 to tissues (main function)
2. Transports CO2 and protons to lungs

Question 3

Describe structure of Hb

Answer 3

Tetrameric protein – 4 subunits (a1,2 & B1,2)
2 identical dimers

Question 4

Hb molecular weight

Answer 4

64500

Question 5

2 Parts of Hb and makeup

Answer 5

• Two parts
haem (prosthetic group)
Globin

haem + globin = Hb

Prosthetic Apo. Holo
Group + Protein = Protein

Question 6

Describe Mb and B globin chains of Hb

Answer 6

• 8 α helical regions
• Similar II ry and III ry structures -
• But differ in I ry structure,

Question 7

a globin chains

Answer 7

• 7 α helical regions

Question 8

• Where is haem found ?

Answer 8

• in a hydrophobic pocket found between E & F helices of the globin.

Question 9

Describe structure of Haem

Answer 9

. 4 pyrrole rings linked together thru methenyl bridges to make cyclic molecule porphyrin ( protoporphyrin IX)

. Protoporphyrin IX binds to Fe2+ to make Haem
. Fe2+ can form five or 6 covalent bonds depending on whether or not oxygen is bound to it

Question 10

Describe bonds in Hb quartenary structure

Answer 10

• Weak ionic and
  H bonds between the dimers

-Mainly strong hydrophobic interactions in between the members of the dimer ( B2-a2 and a1-B1)

Question 11

Oxygenation of Hb leading to conformational changes

Answer 11

Iron moves towards the plane of haem when O2 is bound

Iron moves towards the plane of haem
Movement of the globin chains
Rupture of ionic and H bonds between 2 dimers

In R form ( Relaxed form = O2 bound ), rotation of αβ dimers
Changes in tertiary, quaternary structures
Increase affinity for O2 in other deoxygenated haem

Question 12

4 things that affect ability of Hb to reversible bind to to O2

Answer 12

1. pO2 (through haem-haem interactions)
2. pH (of the environment)
3. pCO2
4. 2,3-bisphosphoglycerate (availability)

Question 13

What is Cooperative oxygen binding ( haem-haem interaction)

Answer 13

Binding of 1 O2 to 1 haem group
Inc. O2 affinity other haem groups in Hb.
Affinity for the last O2 is 300 times more than for 1st.

Question 14

What is 2,3 - bisphosphoglycerate ? How is it synthesised ? 3 functions ?

Answer 14

• Most abundant organic phosphate in RBC
• Synthesized from an intermediate of glycolytic
pathway

• Decreases oxygen affinity to Hb by binding to deoxyHb
• 2,3 BPG promotes efficient release of O2 by stabilizing T form of Hb
• Facilitates release of O2

Question 15

How does 2,3- BPG (a.k.a 2,3 - DPG)modulate O2 release ?

Answer 15

1.when O2 is unloaded (deoxy Hb) b Chains pulled apart 2,3-BPG fits into the central pocket = Since pocket has positively charged amino acids and 2,3 BPG has negatively charged phosphate groups, ionic bond formed
2. Stabilize T form of Hb
3. Reduce O2 affinity

• When oxygenated
2,3-BPG is pushed out

• Presence of 2,3 BPG reduces the affinity of Hb for O2 and shifts the oxygen dissociation curve to the right

Question 16

Describe co2 transport by Hb

Answer 16

Most of CO2 is transported as bicarbonate
15% transported as carbamino- hemoglobin
Hb-NH2 + CO2 reversibly change Hb-NH-COO- + H+
CO2 stabilizes deoxy form of Hb

Question 17

Describe binding of CO to Haem

Answer 17

CO binds tightly but reversibly to haem (forms carbon monoxyhaemoglobin)

Cause Hb to become R form

Increases oxygen affinity

Shifts the oxygen saturation curve to left

Hb is unable to release O2 to tissues Affinity of CO is greater (about 200x) than O2

Affected HB is unable to release O2 to tissues

Question 18

Described globulin chains found In Hb?

Answer 18

• Hb has 2 identical dimers – Eg : (αβ)1 and (αβ)2
α like =α ,ζ
β like = β , γ , δ , ε
(ζ= zeta, γ= gamma, δ= delta, ε = epsilon )

Question 19

What embryonic Hb formed in 1st 3 months of Intra uterine life synthesised in yolk sac

Answer 19

Hb Gower 1 = ζ 2ε 2 (zeta , epsilon)
Hb Portland = ζ 2 γ 2 (zeta, gamma)

Question 20

What is fetal Hb

Answer 20

FetalHb=HbF
- α2 γ2
Main type in fetus and new born (60%)
Levels falls by 6-12 months after delivery
< 2% in normal adults
Synthesis occurs in the fetal liver

Question 21

What is Adult Hb and when is it formed

Answer 21

• HbA is formed from 8th month onwards in the bone marrow
• Gradually replace HbF
• HbA1 = α2 β 2 >90%
• HbA2 = α 2 δ 2 2 %
- HbA2 is the minor adult Hb type

Question 22

Sites of erythropoiesis preconceptual and postnatal

Answer 22

Yolk sac pre week 6
Liver starts ariund week 6 until 36
Spleen starts week 12 till birth
Bone marrow around week 18 onward

Question 23

Functional difference between HbA and HbF

Answer 23

γ chains of HbF lacks (+) vely charged amino acids
HbF binds weakly with 2,3 – BPG
HbF has higher affinity for oxygen

Question 24

What is Glycosylated/ glycated Hb = HbA1C ?

Answer 24

Glucose covalently binds to the β chains
non-enzymatically
Reflects blood glucose concentration over a period
HbA1c test normal - 4.5-5.6% , prediabetes 5.6-6.5, diabetes >6.5

Question 25

Where does Haem synthesis in adults occur

Answer 25

• In adults mainly occur in , Bone marrow –(85%) - at a constant rate Liver - (15%) – variable rate

Question 26

Synthesis of Hb

Answer 26

• Haem in mitochondria • Globin in polyribosomes • Mature RBC lacks mitochondria - unable to synthesize haem

Question 27

5 important points about Haem synthesis

Answer 27

• 8 enzymes • Are irreversible reactions • 1st step and last 3 steps in mitochondria • Rest in cytoplasm • Colourless intermediates are known as Porphyrinogens

Question 28

Steps of Haem synthesis

Answer 28

In mitochondria 1. Succinyl–CoA + Glycine To. ALA Synthase catalyst δ- Amino levulinic acid (ALA). • Committed step and rate limiting step in hepatic porphyrin synthesis • Coenzyme. Pyridoxal phosphate In cytoplasm 2 ALA TO Heavy metals (ex: Lead ) ALA dehydratase Porphobilinogen In cytoplasm 4 Porphobilinogen TO Hyroxymethylbilane TO Uroporphyrinogen III TO Coproprophyrinogen III In mitochondria Protoporphyrin IX Heavy To metals Ferrochelatase Fe2+ added haem

Question 29

What Control haem synthesis - In liver

Answer 29

Excess haem ( Fe 2+). To. Hemin/Hematin (Fe3+)

Question 30

Consequence of Haem synthesis

Answer 30

1. feedback inhibition 2. Repression of ALA synthase 3. Inhibition of transport of ALA synthase from cytosol to mitochondria

Question 31

3 Causes of extra Haem

Answer 31

Drugs (phenobarbital, insecticides, carcinogens)

Question 32

2 ways Control of haem synthesis - In bone marrow,

Answer 32

1. Erythropoietin 2. Availability of intracellular iron

Question 33

Iron-mediated regulation of ALAS mRNA translation

Answer 33

Adequate iron To Causes increased translation of ALA synthase mRNA To haem synthesis stimulated

Question 34

Importance of iron in Hb synthesis

Answer 34

• 2/3rd of body iron stores in Hb • Inadequate iron Iron deficiency anemia Small red cells with low amounts of Hb. Called “ Microcytic hypochromic anemia”

Question 35

What is Porphyrias

Answer 35

• Rare , inherited (or occasionally acquired) • Several types • Classified as hepatic or erythropoeitic porphyrias Deficiency of enzymes of haem synthesis Causes Accumulation and inc. excretion of porphyrins or porphyrin precursors.

Question 36

What causes symptoms vary in phorphyrias

Answer 36

Symptoms vary depending on Affected enzyme  Severity of deficiency  Type – hepatic / erythropoietic “Porphyria “ means purple colour caused by porphyrins in urine.

Question 37

3 clinical features of porphyrias

Answer 37

• Photosensitivity • Neurological symptoms • Urine darkens on exposure to light and air. (purple)