Download MBBS (Bachelor of Medicine, Bachelor of Surgery) 1st year (First Year) Biochemistry ppt lectures Topic 13 Hemoglobin Structure And Function Notes. - biochemistry notes pdf, biochemistry mbbs 1st year notes pdf, biochemistry mbbs notes pdf, biochemistry lecture notes, paramedical biochemistry notes, medical biochemistry pdf, biochemistry lecture notes 2022 ppt, biochemistry pdf.
HEMOGLOBIN:
STRUCTURE AND
FUNCTION
Case 1
A 11-year-old male child was admitted with a history of
having been found unconscious in the bathroom by the elder
brother of the patient.
There was no evidence of associated tonic-clonic
movements, tongue bite, frothing from mouth, vomiting,
bladder, and bowel incontinence or trauma. There was no
history of fever, seizures, headache, vomiting, and substance
abuse prior to this episode.
At the time of admission, patient was unresponsive. Pupils
were normal size and well reacting to light, and plantar reflex
was extensor bilaterally and systemic examination was
normal.
Patient was intubated, mechanically ventilated, and was
started on antiedema measures and other supportive
treatment
MRI: bilateral gyral swelling of the frontal and parietal lobes.
Patient improved and was extubated on the fourth day of
admission and was discharged in satisfactory condition after
seven days without any neurological sequelae.
Ref: Sharma S, Gupta R, Paul BS, et al: Accidental carbon monoxide poisoning in our homes.
Indian J Crit Care Med 2009;13:169-170.
Case 2
A 25-year-old male was found lying unconscious and brought
out after breaking open the bathroom door after one hour.
Similar Examination and MRI like Case 1
He had residual hypoxic damage in the form of persistent
vegetative state and was discharged to a domiciliary care on
request.
Discussion
Gas geysers have emerged as a cost-effective efficient
method for heating water at homes. Gas geysers run on
LPG, the combustion of which leads to generation of CO,
hydrocarbons, and nitrogen oxides.
CO toxicity occurs by competitive binding of CO to the
hemoglobin heme groups shifting the oxygen-
hemoglobin dissociation curve to the left.
The predilection for the globus pallidus may relate to
hypotensive effect of CO poisoning in the watershed territory
of the arterial supply.
Treatment: ??
Hints:
Competitive Inhibitor
Affects oxygen dissociation curve
Learning objectives
Structure of Hemoglobin
Binding of oxygen to Hemoglobin
Binding of CO to hemoglobin
Importance of Oxygen
Why these many symptoms by inhaling a
gas?
ANOXIA
Oxygen needs to be transported from lungs to tissues
efficiently to protect against anoxic episodes
What is the mechanism for this efficient transport?
What is the biomolecule responsible and its characteristics
that supports this function?
Hemoglobin(Hb)
Hemoglobin
Quaternary structure
Hemoglobin
Heme(4)
Globin(4)
Heme : Prosthetic group
Globin: Protein part
Protoporphyrin
ring
HbA: 2, 2
Fe2+
Structure of Heme
Iron containing pigment heme is attached to protein globin
Heme is iron porphyrin complex
called Iron protoporphyrin IX
Conjugated double bonds
Red color to Heme.
Functional form Iron in Heme is-
Ferrous form(Fe++)
Reduced state
Structure of Globin
Adult Hemoglobin has 4 Polypeptide chains : 2 and 2
Heme Pocket
Heme Pocket is a crevice/
hol ow hydrophobic area
Formed in the interior of
Globin subunits
Heme group is tucked
between E and F helices
of Globin subunit.
Amino acids in Globin chain are identified by Helix name
and Position of a.a in that helix.
E7 His ( Distal His), F8 His ( Proximal His)
Oxygen binding of Hemoglobin
Iron has 4 covalent bonds
with pyrrole rings, Fifth
coordination bond with
proximal histidine(F8),
Sixth coordination bond
with divalent oxygen
Divalent oxygen is linked to
Fe++ of Heme and
imidazole group of Distal
histidine(E7)
Where did CO bind in Case 1 and 2??
Hint :
Competitive binding
Affects Mitochondrial ETC
(Respiratory Chain/
Cellular respiration)
To generate AT P
(Oxidative Phosphorylation)
Treatment for CO Poisoning
Treatment includes immediate removal of the victim from the
exposure and administration of high-flow or 100% oxygen by
a non-rebreather reservoir oxygen mask
Prevention: The geyser should not be switched on after
locking the door from inside, ventilation should be kept open
Gas geyser unit should be placed outside the bathroom with
a hose of hot water going inside.
References
1. Victor W. Rodwell, David A. Bender, Kathleen M. Botham, Peter J. Kennel y, P. Anthony Weil.
Harper's Illustrated Biochemistry, 30th Edition
2. Denise R. Ferrier; Lippincott Illustrated Reviews Biochemistry, 7th Edition
3. Kasper, Fauci, Hauser et al., Harrison's Principles of Internal Medicine, 19th Edition
Why 2,3 BPG reduces in stored blood?
During storage of RBCs, large amounts of lactate are formed
and blood pH drops rapidly.
When the pH falls below 7.2, the bisphosphoglycerate
phosphatase wil be activated and the normally high
concentration of 2,3-DPG is rapidly depleted
Duhm J, Gehrlach E. Metabolism and function of 2,3- diphosphoglycreate in red blood cells.
Greenwalt TJ, Jamieson GA, editors. The human red cell in vitro. New York: Grune & Stratton; 1974. p. 111-48.
Where was 2,3 BPG in Glycolysis?
Was it 1,3 BPG or 2,3 BPG?
What do 2,3 BPG has to do with
Oxygenation and Oxygen transport??
In Hb 4 polypeptide chains
are visualized as two
identical dimers, ()1
and ()2 held by
Ionic bonds and
Hydrophobic interactions,
Two dimers are linked to
each other by weak polar
bonds.
Taut and Relaxed forms of Hb
T Form of Hb
R Form Of Hb
Deoxy Hb is in T form
Oxy Hb is in R form binds
binds with CO2,H+ and
only with Oxygen
2,3BPG
T form has salt bridges
Salt bridges are broken in
linked in between the dimer between the dimer subunits
subunits
during oxygenation of Hb.
More constrained form
Less constrained form
T form has low affinity for R form has higher affinity
Oxygen
for Oxygen
T form of Hb predominates R form of Hb predominates
in low pO2
at high pO2
How does these bonds break on
Oxygenation?
Changes in Hb on oxygenation
Fe moves into plane of of heme
22 moves 150 relative to 11
(0.3A0 to 0.1A0 )
Features of oxygenation of Hb
Oxygen links to Ferrous form of Iron, of Heme ( Reversible,
non-enzymatic, no oxidation of Ferrous)
One Hb molecule with 4 Heme can bind to four O2
molecules
Shows c operative binding like allosteric regulatio
Fol ows Hil s equation
Due to tetrametric structure o Hb
Makes it efficient in oxygen transport
How cooperative binding mechanism
makes Hb efficient in oxygen transport
Allows 100% saturation at pO2 much lower than
what it actually requires
Hemoglobin picks up the largest possible load of
Oxygen in the lungs, and delivers the Oxygen
where and when needed.
Role of 2,3 BPG in release of oxygen
One molecule of 2,3-BPG binds
to a pocket, formed by the two -
globin chains, in the center of
the deoxyhemoglobin tetramer
This pocket contains several
positively charged amino
acids(lysine, valine) that form
ionic bonds with the
negatively charged
phosphate groups of 2,3-
BPG.
Stabilizes T form of deoxyHb
Consequence of Transfusing stored blood
Hemoglobin deficient in 2,3-BPG thus acts as an oxygen
"trap" rather than as an oxygen transport system.
Transfused RBCs are able to restore their depleted supplies
of 2,3-BPG in 6?24 hours.
However, severely il patients may be compromised if
transfused with large quantities of such 2,3-BPG?"stripped"
blood
The maximum storage time for red cells has been
doubled (21 to 42 days, with median time of 15 days)
by changes in H+, phosphate and hexose sugar
concentration
Response of 2,3-BPG levels to chronic
hypoxia or anemia
Al osteric effect of 2,3 BPG
on oxygen affinity
2,3 BPG concentration
increases in RBC in
hypoxia/ anemia
HbF: Low affinity for 2,3
BPG
Thank You!
This post was last modified on 05 April 2022