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BIOCHEMICAL ASPECT OF BLOOD-a
BIOCHEMICAL ASPECT OF BLOOD-a
Sofro
Dept.of Biochemistry, Fac. of Medicine
YARSI University
Teaching aims
Reference:
Murray K et al. 2000. Harper’s Biochemistry, 25th ed &
other lecture sources
Core topics
Introduction
Composition and main functions of blood
Plasma and its proteins
Hemostasis and thrombosis
Introduction
Respiration
Nutrition
Excretion
Maintenance of normal acid-base balance
Regulation of water balance
Regulation of body temperature
Defense against infection by WBC &
circulating antibodies
Transport of hormones & regulation of
metabolism
Transport of metabolites
Coagulation
Composition
Solid elements : RBC, WBC, Platelets
Liquid medium : plasma consisting of water,
electrolytes, metabolites, nutrients, proteins,
hormones, etc.
Water & electrolyte composition of
plasma is practically the same as that of all
extracellular fluids
Once the blood has clotted (coagulated),
the remaining liquid phase (called serum)
lacks of the clotting factors (including
fibrinogen)
Composition of Blood
19-9
Red blood cells (erythrocytes)
A GAL
B
Precursor
B Gal substance
FUC
Genes & their product in ABO blood
group system
Gene H : fucosyltransferase
Gene A : N-acetylgalactosamine
glycosyltransferase
Gene B : galactosyltransferase
Gene O : inactive enzyme
Gene product Antigen Gene product
Antigen
H&A
Tr-A
Ps H
r u Tr-B
e b Tr-H H&B
c s O
u t
r a hh H
s n
o c Precursor
r e substance
RBC Precursor Structure
RBC
Glucose
Galactose
Precursor
Substance
(stays the N-acetylglucosamine
same)
Galactose
Source: cls.umc.edu/COURSES/.../ABOsystem.ppt
Formation of the H antigen
RBC
Glucose
H antigen Galactose
N-acetylglucosamine
Galactose
Fucose cls.umc.edu/COURSES/.../ABOsystem.ppt
Formation of the A antigen
RBC
cls.umc.edu/COURSES/.../ABOsystem.ppt
Glucose
Galactose
N-acetylglucosamine
Galactose
N-acetylgalactosamine
Fucose
Formation of the B antigen
RBC
cls.umc.edu/COURSES/.../ABOsystem.ppt
Glucose
Galactose
N-acetylglucosamine
Galactose
Galactose
Fucose
Genetics
Greatest Least
amount of H amount of H
O>A2>B>A2B>A1>A1B
cls.umc.edu/COURSES/.../ABOsystem.ppt
A A
A A
Group O Group A
Many H Fewer A
antigen sites H antigen
sites
cls.umc.edu/COURSES/.../ABOsystem.ppt
Plasma and its proteins
Plasma proteins
Total plasma protein approx. 7.0-7.5 g/dl
A complex mixture of simple & conjugated
proteins such as glycoproteins & various
types of lipoproteins, thousands of antibodies
Can be separated by:
sodium or amm. sulfate into three major
groups fibrinogen, albumin & globulins
electrophoresis using cellulose acetate into
five bands albumin, 1, 2, & globulin
Cont.
Concentration of plasma protein is important in
determining the distribution of fluid between
blood & tissues
Osmotic pressure (oncotic pressure) exerted by
plasma protein is approx. 25 mm Hg.
Hydrostatic pressure in arterioles is approx.
37 mm Hg a net outward force of about 11
mm Hg drives fluid out into interstitial spaces.
Hydrostatic pressure in venules is approx. 17
mm Hg a net force of about 9 mm Hg
attracts water back into circulation
Cont.
Antiprotease (antichymotrypsin, a1 –
antitrypsin, a2 macroglobulin,
antithrombin)
Blood clotting (various coagulation
factors, fibrinogen)
Hormones
Immune defence (Ig, complement
proteins, b2-microgloblin)
Involvement in inflammatory
responses (acute phase response
protein eg. C-reactive protein, a1-
acid glycoprotein
Oncofetal (a1-fetoprotein = AFP)
Transport or binding proteins such
as:
Cont.
albumin for bilirubin, FFA, ions, metals,
metheme, steroids, other hormones, variety
of drugs
Ceruloplasmin contains Cu but albumin is
more important in physiological transport of
Cu
Corticosteroid-binding globulin (transcortin)
Haptoglobin binds extracorpuscular Hb
Liproproteins (chylomicron, VLDL, LDL,
HDL)
Cont.
Hemopexin
Retinol-binding protein
Sex hormone-binding globulin
Thyroid-binding
Transferrin
Transthyretin (formerly pre albumin, binds
T4 & forms a complex with Retinol-binding
protein)
Detail functions of some plasma protein
Albumin:
Major protein of human plasma (3.4-4.7 g/dL)
Some 40% in plasma, 60% in extracellular space
Synthesized in liver as preproprotein, depressed in
a variety of diseases, particularly those of liver
(decreases albumin/globulin ratio)
Responsible for 75-80% of osmotic pressure of
human plasma
Ability to bind various ligands (include FFA, Ca,
certain steroid hormones, bilirubin etc.
Play an important role in transport of Cu, drugs
Cont.
Haptoglobin:
A plasma glycoprotein that binds
extracorpuscular Hb in a tight
noncovalent Hb-Hp complex
Prevent loss of free Hb into kidney
Its plasma levels are of some
diagnostic use low level in
hemolytic anemias
Cont.
Transferrin:
a 1-globulin, a glycoprotein, synthesized
in liver
Plays an important role in the body’s
metabolism of iron (two mol of Fe3+ per
mole of transferrin) diminishes potential
toxicity of free iron
Plasma concentration is approx. 300
mg/dL can bind 300 µg of iron per dL
(Total Iron Binding Capacity of plasma)
Ceruloplasmin (Cp)
2-globulin
Binds copper (Cu)
Exhibits a copper-dependent oxidase
activity
Low levels of Cp are associated with Wilson
disease
Tissue levels of Cu & certain other metals
are regulated in part by metallomethionins
(small protein found in the cytosol of cells
particularly liver, kidney & intestine)
1-Antiproteinase (1-antitrypsin)
Synthesized by hepatocytes &
macrophages
Principal serine protease inhibitor of
human plasma inhibits trypsin,
elastase & certain other proteases
Deficiency of this protein has a role in
certain cases (approx. 5%) of
emphysema
2-Macroglobulin
A large plasma glycoprotein
Comprises 8-10% of the total plasma
protein in human
Synthesized by a variety of cell types,
including monocytes, hepatocytes &
astrocytes.
Binds many proteinases (an important
panproteinase inhibitor)
Binds many cytokines
Immunoglobulin
Play a major role in the body’s
defence mechanism
Synthesized by B lymphocytes
Immunoglobulin (Ig)
IgD 2 2 22 18 %
XII XIIa
HK Extrinsic pathway
VII
Ca 2+
XI XIa
VIIa/Tissue factor
Ca 2+
IX IXa
VIII VIIIa Ca 2+
PL
X Xa X
V Va Ca 2+
PL
Prothrombin Thrombin
Prothrombin Thrombin
XIII
Fibrinogen
XIIIa
Fibrin monomer
Fibrin polymer
Cross-linked
Fibrin polymer
Extrinsic pathway