Download What makes up our blood?

Chapter 19
blood biochemistry
What makes up our blood?
What makes up our blood?
• PLASMA – This is the yellowish liquid portion of blood
that contains electrolytes, nutrients and vitamins,
hormones, clotting factors, and proteins such as
antibodies to fight infection.
• RED BLOOD CELLS (Erythrocytes) – The most
abundant cells in our blood; they are produced in the
bone marrow and contain a protein called hemoglobin
that carries oxygen to our cells.
• WHITE BLOOD CELLS (Leukocytes) – They are part of
the immune system and destroy infectious agents called
pathogens.
• PLATELETS (Thrombocytes) – The clotting factors that
are carried in the plasma; they clot together in a process
called coagulation to seal a wound and prevent a loss of
blood.
We will learn:
- Composition of plasma
- Metabolism of Red blood cells
Section 1
Composition of plasma
• Composition
• Non-protein nitrogen (NPN)
• Plasma proteins
Components of Plasma
• Liquid part of blood, made up of 92% water, 8%
soluble substances.
• soluble substances include organic compounds
and inorganic compounds.
• Electrolyses are the major inorganic compounds
including Na+, K+, Ca2+, Mg2+ and Cl-, HCO3- etc,
which are responsible for maintain of crystal
osmotic pressure, acid-base balance, and normal
neuromuscular excitability.
Components of Plasma
• Organic compounds include proteins,
organic nutrients, hormones and waste
products.
• NPN (non-protein nitrogen): It includes
urea, uric acid, creatinine, creatine,
bilirubin and ammonia, the nitrogen in
which is termed NPN.
• 50% of NPN is blood urea nitrogen (BUN).
Significance of NPN
• NPN has little nutrition and is transported to the
kidneys for excretion from the urine.
• NPN is an index of renal function.
• 50% of NPN is blood urea nitrogen (BUN),
clinically, determinate BUN rather than NPN to
reflect renal function.
Difference between plasma and serum
• Serum: After blood clotting, the liquid
separated from the clot.
No fibrinogen
• Serum has the same composition as
plasma except for fibrinogens, which are
used up during clotting.
Classes of Plasma Proteins
• Plasma proteins are very complicated mixture
• Main protein can be divided into:
-Albumins (60%)
-Globulins (35%)
-Fibrinogen (4%)
Separation of plasma protein
• The plasma proteins are usually classified
according to the source, separation methods
and physiological functions.
• The general methods of proteins separation
are electrophoresis and ultracentrifugation.
Separation of plasma protein
electrophoresis
• It is the most common method to separate
plasma proteins.
• Separate proteins based on their physical
characteristics, such as pI (Isoelectric point),
molecular weight and size.
Separation of plasma protein
electrophoresis
- Using cellulose acetate electrophoresis, plasma
protein can be separated into six groups.
anode
cathode
Albumin α1globulin α2globulin βglobulin fibrinogen γglobulin
If serum is separated using this method, how
many bands will be appear ? What are they?
Section 2
Metabolism of red blood cells
Structure of RBC
-Small and highly specialized disc
-Thin in middle and thicker at edge
Red blood cells (erythrocytes)
• They are the most important cells in blood, formed
through direct differentiation of haemopoietic stem
cells in marrow.
• Erythropoiesis refers to as the production of
erythrocytes.
• The procedure of cell transformation: proerythroblast,
erythroblast, intermediate erythroblast, later
erythroblast, reticulocyte.
• The overall transformation from the proerythroblast to
reticulocyte involves a reduction in cell size, an
increase in cell number and the synthesis of
hemoglobin.
Metabolic characteristics of
mature erythrocytes
• Mature erythrocyte does not possess other
organelles, except plasma membrane and
cytoplasma.
• Its metabolism is simpler and only contains four
basic classical pathways: glycolysis, pentose
phosphate pathway, adenine nucleotide
metabolism and 2, 3-BPG shunt.
• The task of these metabolisms is to produce the
necessary cofactors ( ATP, NADPH and NADH) for
maintaining its osmotic balance and
electroneutrality and fighting oxidative stresses.
Metabolic characteristics of
mature erythrocytes
glycolysis
• Erythrocytes consume about 30g glucose each day,
of which 90-95% enter into glycolysis and 2, 3-BPG
shunt, 5%-10% through pentose phosphate pathway.
• Mature erythrocytes depend on glycolysis for ATP
production.
• ATP is used to maintain the biconcave disk shape,
ion balance, and so on.
Metabolic characteristics of
mature erythrocytes
(1,3-BPG)
(2,3-BPG)
2,3-BPG pathway
Role of 2,3-bisphosphoglycerate (2,3-BPG)
• Activity of diphosphoglycerate mutase is much
high than that of diphosphoglycerate phosphatase,
so the concentration of 2,3-BPG is very high in
erythrocytes.
1 heme : 1 O2
Release
oxygen
T state
T state
R state
R state
Role of 2,3-bisphosphoglycerate (2,3-BPG)
• 2,3-BPG is a potent allosteric effector on the oxygen
binding properties of hemoglobin.
• In the deoxygenated T conformer, 2,3-BPG can
occupy a cavity which locate in the center of the
hemoglobin.
• 2,3-BPG stabilizes the T state of hemoglobin,
causes the release of more oxygen
• Its main function is regulating the ability of
transporting oxygen of hemoglobin.
Biochemical features of RBC
•
•
•
•
Lifespan is about 120 days
Lack nuclei, mitochondria, and ribosomes
Essential component is hemoglobin
Function
-Transport oxygen from lungs to tissues
and carbon dioxide from tissues to lungs
Hemoglobin
• Consist of 4 globular protein subunits:
– each with 1 molecule of heme
– each heme contains 1 iron ion
– Each iron ion with 1 O2
• Iron ions easily:
1 Hb : ? O2
1 Hb : 4 O2
– associate with oxygen (oxyhemoglobin)
– or dissociate from oxygen (deoxyhemoglobin)
Hemoglobin
Biosynthesis of hemoglobin
Globin: The synthesis is similar to other
proteins
Consist of 4 subunits
(2+2 )
Heme: is not only the prosthetic group of
Hb, but also the prosthetic group of
myoglobin, cytochrome and
peroxydase.
Heme synthesis
• The principal sites of synthesis are erythroid
cells (~85%) and hepatocytes (accounting for
nearly all the rest of heme synthesis).
• Mitochondrion and cytoplasm are involved in
heme synthesis.
• Materials needed in synthesis are succinylCoA, glycine and Fe2+.
• Synthesis of heme can be divided into four
steps.
Heme synthesis pathway
Heme synthesis pathway
The First step
• take place in
mitochondria
-aminolevulinate
• ALA synthase
synthase
catalyze this reaction
• It is the rate-limiting
reaction in heme
synthesis
Regulation of heme biosynthesis
• Negative Feedback control: heme inhibit
synthesis and activity of ALA synthase.
• Erythropoietin(EPO): increase heme
synthesis to carry more oxygen.
EPO Scandal
• EPO is a hormone involved in red blood cell production
and increases the body's oxygen delivery. For this reason,
it's usually used in endurance sports like cycling,
distance running, and boxing.
• However, EPO is thought as a blood doping by the World
Anti-doping Agency. Although EPO has been banned
since the 1990s, the first screening test was used at the
2000 Summer Olympic Games in Sydney.
EPO Scandal
Lance Armstrong
•
He is an American former professional
road racing cyclist.
•
He had won the Tour de France a record
seven consecutive times between 1999 and
2005.
•
On August 24, 2012 it announced a lifetime
ban from competition, applicable to all
sports which follow the US Anti-Doping
Agency (USADA) code, as well as the
stripping of all titles won since August
1998.[ Because USADA detected EPO in
his urine samples which keeped before.
The formed elements in blood include
,
and
.
The nitrogen in ,
,
,
and
which is an index of
function.
is termed NPN,
Difference between plasma and serum is plasma
containing
, which is absent in serum.
The general methods of proteins separation
are
and
.
Using cellulose acetate electrophoresis, serum
protein can be separated into
,
,
cathode ).
and
groups, they are
respectively (from anode to
,
• Which the following statements about serum
protein separation by electrophoresis is not right?
A. It is the most common method to separate
plasma proteins.
B. It separate proteins based on their pI, molecular
weight and size.
C. After electrophoresis, there are six bands on
cellulose acetate membrane.
D. The band nearest to anode is albumin.
E. The migration speed of -globulin is slowest.
In mature RBC,
pathway produces ATP. Pentose
Phosphate pathway can provide
.
In mature RBC, there is a
shunt, the product of this
pathway can stimulate hemoglobin to release more
.
The function of hemoglobin is to Transport
to tissues and
from tissues to lungs .
from lungs
Heme synthesis mainly occurs in
and
of cells.
The synthesis Materials include ,
and
, the
rate-limiting enzyme is
.