Hb structure and globular proteins

Question 1

def of the heme

Answer 1

ferrous iron ( Fe +2) can bind to O2 reversibly + protoporphyrin IX

Question 2

heme is positioned in ………….( why ? )

Answer 2

• in adeep hydrophobic pocket
  -to protect it from being oxidized to ferric ( Fe +3 ) which can’t bind O2

Question 3

illustrate the structure of porphyrin

Answer 3

• 4 pyrrole rings linked by methenyl bridge ( -CH)
• conjugated doudle bonds absorb light and colored
• form complex with metal iron ( Fe or Mg )
• conjugate with protein to form hemoprotein
• iron form 5 or 6 coordination bond :
  4 bonds with N of pyrrole ring
  5th with proximal histidine
  6th with O2
  ( 5th , 6th are perpendicular to the porphyrin ring “ one on each side of the planar porphyrin ring “ )

Question 4

when O2 bind to iron , cange the color from ……. of the ……form to the ……of the ……form .

Answer 4

dark purple - deoxy
bright red - oxy

Question 5

def of hemin ( hematin , oxidized heme )

Answer 5

ferric iron ( Fe+3 ) + protoporphyrin

Question 6

def of porphyrinogen

Answer 6

reduced ( hydrogenated ) porphyrin contain methylene ( CH2) not methenyl .
- can’t absorb light and colorless

Question 7

illustrate the structure of myoglobin

Answer 7

conjugated protein : monomeric
one globin cahin + one heme containing
- 1ry structure :
globin chain 153AA
-2ry structure :
globin chain 8 α helices ( ABCDEFGH)
terminated by proline or β bend and loops stabilized by hydrogen bond and ionic bond
-3ry structure : globular
surface AA prevent association of Mb
nonpolar AA in the interior except :
* proximal histidine F8 bind directly to the Fe+2
* the distal histidine E7 stabilize the binding of O2 to Fe+2
-4ry structure: no 4ry structure

Question 8

illustrate the structure of Hb

Answer 8

hetero tetramer
4 globin chain 2 α and 2 non α chain + 4 heme groups
- 1ry structure :
α chain = 144 AA
β chain = 146 AA
- 2ry structure :
α chain = 7α helices
β chain = 8 α helices
- 3ry structure : globular
polar AA surface ( except His F8 = 93 , His E7 =64 on the interior )
surface AA of Hb provide hydrogen bonds and non polar interaction with other subunits
non polar in the interior
- 4ry structure :
in Hb 2 identical dimer ( αβ )1 and ( αβ )2
multiple interchain hydrophobic interaction form strong associations between α subunits and β subunits in the dimer .
in contrast the two dimer are held together by weaker polar bond . which allow presence of relative different positions in deoxyhemoglobin as compared to oxyhemoglobin

Question 9

list difference of location between myoglobin and Hb

Answer 9

myoglobin : cardiac and skeletal ms
Hb : RBCs

Question 10

what’s the function of myoglobin ?

Answer 10

• it can store O2 in ms
• facilitate movement of O2 in ms

Question 11

what’s the function of Hb ?

Answer 11

• transport O2 from the lung to all tissue
• transport 15% of Co2 from the tissue to the lung to be expired
• it has buffering effect in blood

Question 12

list the type of :
myoglobin
Hb

Answer 12

myoglobin = one type
Hb =
Hb A ( adult Hb ) α2,β2
Hb A1c ( α2 , β2 - glucose )
Hb F ( fetal Hb ) α2 γ2
Hb E ( embryonic ) 2α 2ε

Question 13

list Hb A ( adult Hb ) α2,β2

Answer 13

• the majority 98% of normal adult Hb A is Hb A1 formed of globin made of 2α and 2β subunits
• the minority 2% is Hb A2 contain globin subunits 2α & 2δ subunits

Question 14

list Hb A1c ( α2 , β2 - glucose )

Answer 14

form 4 - 6.5 % of Hb A1
conjugation of glucose with N terminal of β chain .
naming derives from Hb A being separate on cation exchange chromatography.

Question 15

what’s the relation between Hb A1c and DM?

Answer 15

-RBCs life span = 120 days
-measuring conc of Hb A1c indicate the state of patient blood glucose for 4 months
- long term screening to avoid complication of DM

Question 16

list Hb F ( fetal Hb ) α2 γ2

Answer 16

• only in the fetal blood
• replaced by Hb A1 during 1st 6 months after birth
• it’s higher affinity to O2 from adult

Question 17

list Hb E ( embryonic ) 2α 2ε

Answer 17

converted to fetal after 6 months of gestation

Question 18

def of oxygen dissociation curve

Answer 18

a plot of percentage saturation measured at different O2 partial pressures (PO2)

Question 19

……..higher affinity to O2 at all PO2 than Hb

Answer 19

myoglobin

Question 20

PO2 ( of myoglobin ) needed to achieve half saturation of binding site is …….. while to achieve 100% saturation is …….

Answer 20

P50 is 5 mm Hg
20 mm Hg

Question 21

myoglobin dissociation curve is a ……..shape

Answer 21

hyperbolic ( Mb bind to single O2)

Question 22

PO2 ( of Hb ) needed to achieve P50 is ……
while to achieve 100% saturation is ……..

Answer 22

26 mm Hg
100 mm Hg

Question 23

hemoglobin dissociation curve is a ……..shape

Answer 23

sigmoidal

Question 24

subunits cooperate in binding O2 =

Answer 24

the binding of an Oxygen molecule at one subunit increase the oxygen affinity of the remaining subunits in the same Hb tetramer