Lecture 4 RBC metabolism & Hb synthesis.ppt

Lecture 4 RBC metabolism & Hb synthesis.ppt

1. Lecture 4
Red Cells metabolism
ElraziUniversity
Faculty of MLS
Dept of Haematology

2. Red Blood Cells function
The main function of red cells is to carry
O2 to the tissues and return CO2 from
tissues to the lungs
In order to achieve this gaseous exchange
they contain the specialized protein
“Haemoglobin”
Each red cell contains about 640 million
haemoglobin molecules

3. RBC delivering haemoglobin from the
lungs to the microcirculation and back
every 11 seconds, and keeping it in a
functioning state for 120 days
The total journey throughout its 120 days
lifespan has been estimated to be 300
mile
The red blood cell's major function is to
carry hemoglobin and protect it so it can
function as an oxygen transporter for a
prolonged period

4. Effective function of the red blood cell depends on:
-[1] its strongly negative surface charge (derived
from surface glycoproteins) which permits it to
repulse other circulating cells, thereby
preventing "clumping“
-[2] its unique biconcave shape, which is highly
flexible and permits rapid flow of the cells
through capillaries; and
-[3] its ability to prevent oxidative stress to the
hemoglobin molecule, thereby maintaining the
four iron atoms on each hemoglobin molecule in
the ferrous (Fe2+) state, in which they are able
to bind oxygen reversibly

5. Since the cell contains no nucleus and has
no capacity to synthesize proteins,
damaged molecules cannot be replaced
during the red blood cell's long lifespan.
The shapeof the cell is maintained, the
cell's volumeis regulated, and hemoglobin
and other important molecules in the cell
(such as membranelipids and structural
proteins) are protected from oxidation by
enzyme systems that are driven by
glucose metabolism

6. Glucose catabolism in the red cell, either
via the
1) Embden-Myerhof pathwayor the
2) hexose-monophosphate shunt
(Pentose Phosphate Pathway PPP)

7. Red Blood Cells Metabolism
Pathways & enzymes

8. Embden-Myerhof Pathway
inthe Red Blood Cell
As do most cells in the body, red blood cells
anaerobicallycatabolyzeglucose to lactic
acid via the Embden-Myerhof, or glycolytic,
pathway.
Since red blood cells do not store glycogen,
they must constantly catabolyzeglucose
from the bloodstream via this pathway and
the hexosemonophosphateshunt as a
source of energy

9. The Embden-Myerhofpathway serves
three functions in the RBC:
[1] ATP production; [Energy]
[2] 2,3 diphosphoglycerate(2,3 DPG)
production [regulation of O
2-Hb binding]
[3] NADH production. [reducing agent]

11. ATP:The glycolyticpathway produces the
red cell's major fuel source, ATP
(glucose + 2 ADP = 2 lactic acid + 2 ATP).
While several enzymes depend on ATP,
one in particular is critical to red blood cell
function: the Na
+
/K
+
pump.

12. The red blood cell's volume is maintained in
large part by the Na
+
/K
+
ATPasein its
plasma membrane, which extrudes Na+ from
the cell together with osmoticallyobligated
water molecules.
In the absence of ATP, Na
+
is retained and
the cell swells. Swollen red blood cells
cannot bend into the microcirculation and
are eliminated in the red pulp of the spleen.

13. 2,3 DPG. The glycolytic pathway produces an
intermediary compound, 2,3 DPG, which exerts
an important functional effect on hemoglobin's
affinity for oxygen.
In most cells, 2,3 DPG is a trace constituent,
but in the red cell, it accounts for about two
thirds of the total cell phosphorus.
The precursor to 2,3 DPG is 1,3 DPG, which in
most cells is quickly converted to 3
phosphoglycerate + ATP.


14. In the red blood cell, the enzyme DGP
synthase convert 1,3 diphosphoglycerate
to 2,3 diphosphoglycerate, which is then
converted to 3 phosphoglycerate
This alternative pathway is called the
Rapoport-Luebering shunt.
The rate of 2,3 diphosphoglycerate
production is controlled by the rate of
glycolysis.
2,3 DPGbind to the hemoglobin molecule
and favoring the low oxygen affinity state

15. NADH:During the course of glycosis, the
oxidized form of nicotinamide dinucleotide
(NAD+) is reduced to NADH.
NADHis an essential cofactor for the
enzyme methemoglobin reductase, which
provides one of the pathways by which
methemoglobinis reduced to native
hemoglobin.
(Methaemoglobin produced by oxidation of
approximately 3% of haemoglobin each day)

16. When ferrous(Fe
2+
) iron in hemoglobin is
oxidized to the ferric(Fe
3+
) state through
oxidative stresses on the molecule, it is
reconverted to the ferrous state by the
enzyme methemoglobin reductase.
NADH, which serves as an electron donor,
is an essential cofactor in this reaction.

17. Hexose-Monophosphate Shunt
Under homeostatic conditions, about 10%
of the glucose utilized by the red blood cell is
catabolizedvia the hexose-monophosphate
shunt, or ( pentose phospatepathway).
This pathway provides an additional critical
protection against oxidative damage to the
cell from toxic peroxideradicals. It does so
through the generation of the reduced form
of nicotinamideadenine dinucleotide
phosphate (NADPH).

18. The first enzyme in this pathway is glucose-6-
phosphate dehydrogenase(G6PD)which oxidizes
glucose-6-phosphate to 6-phosphogluconate.
NADP
+
, which serves as a cofactor in this reaction, is
reduced to NADPH.
NADPH is a cofactor for glutathione reductase,
which then reduces oxidized glutathione (GSSG) to
the reduced form (GSH).
GSH serves as a cofactor for the enzyme glutathione
peroxidase, which reduces various peroxidesto
water.

21. Methaemoglobinaemia
It is a state in which circulating Hbis present
with iron in the oxidized state (Fe
+3
) instead
of the usual Fe
+2
state.
It may arise because of hereditary
-deficiency of NADH
-Structurally abnormal haemoglobin (HbM)
If Methemoglobinlevel is above 10%, the
patient appear cyanotic, having a blue
color, especially in the lips and fingers

22. The End
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