(4) biokimia sistem hematologi english

8/10/2019 (4) Biokimia Sistem Hematologi English

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Department of Biochemistry

Faculty of Medicine UNHAS

Biomedical Science 2

Makassar, 9thMarch 2011


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Introduction

Plasma proteins Membrane of erythrocytes

Structure and function of Hemoglobin

Metabolism of Erythrocytes

Metabolism of LeukocytesClinical correlations


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Human blood constitutes about 8% of the

bodysweight

Consists of cellsand cell fragments in anaqueous medium, the blood plasma

The proportion of cellular elements, known

as hematocrit, in the total volume isapproximately 45%


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The blood plasma is an aqueous solution

of electrolytes, nutrients, metabolites,

proteins, vitamins, trace elements, andsignaling substances

The fluid phase of coagulated blood is

known as blood serum It differs from the plasma in that it lacks

fibrin and other coagulation proteins


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Quantitatively, proteinsare the most

important partof the soluble components

of the blood plasmaWith concentrations of between 60 and 80

g/L, they constitute approximately 4% of

the bodys total protein


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Some 100 different proteins occur in

human blood plasma.

Based on their behavior duringelectrophoresis they are broadly dividedinto five fractions: albuminsand 1, 2,

and-globulins


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Under the microscope, the red blood cell appears

to be a red disc with a pale central area (biconcave

disc)

The biconcave disc shape serves to facilitate gasexchange across the cell membrane

The membrane proteins: maintain the shape of the red blood cell

allow the red blood cell to traverse the capillaries with very

small luminal diameters to deliver oxygen to the tissues


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The interior diameters of many capillariesare smaller than the approximately 7.5m

diameter of the red cell

The spleen is the organ responsible for

determining the viability of the red blood

cells

Erythrocytes pass through the spleen 120times per day


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The elliptical passageways through thespleen are approximately 3m in diameter,

and normal red cells traverse them in

approximately 30 seconds

Damaged red cells that are no longer

deformable become trapped in the

passages in the spleen, where they aredestroyed by macrophages


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On the cytoplasmic side of the membrane,

proteins form a two-dimensional lattice that

gives the red cell its flexibility

The major proteins are spectrin, actin,

band 4.1, band 4.2, and ankyrin.


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The most important task of the red blood

cells (erythrocytes) is to transport

molecular oxygen (O2) from the lungs intothe tissues, and carbon dioxide (CO2) from

the tissues back into the lungs

To achieve this, the higher organisms

require a special transport system, since

O2 is poorly soluble in water


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Only around 3.2 mL O2 is soluble in 1 L

blood plasma. By contrast, the protein

hemoglobin (Hb), contained in theerythrocytes, can bind a maximum of 220

mL O2 per liter70 times the physically

soluble amountThe Hb content of blood:

140180 g/L in men

120160 g/L in women


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Adult hemoglobin is a tetrameric

hemeprotein (quartenery structure) found

in erythrocytes where it is responsible for

binding oxygen in the lung andtransporting the bound oxygen throughout

the body where it is used in aerobic

metabolic pathwaysThe tetramers are composed of pairs of

two different polypeptide subunits

The subunits are -, -, -, -chain


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The haemoglobin molecule is a tetramer consisting of 4 polypeptide

chains, known as globins, which are usually:

2 alpha chains that are each 141 amino acids long

2 beta chains that are each 146 amino acids long

Attached to each chain is an iron-containing molecule known as haem


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Adult hemoglobin is a tetrameric hemeprotein(HbA1, 22, 97%), (HbA2, 22, 2-3%)

Two other forms occur during embryonic and

fetal development the first three months, embryonic hemoglobins

are formed, with the 22and 22

up to the time of birth, fetal hemoglobin then

predominates (HbF, 22)

during the first few months of life, it is replaced

gradually by HbA


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Oxygenated dan Deoksigenated Hemoglobin The subunit of deoxyhemoglobin are held

together by salt bonds between the

polypeptide Upon oxygenation the salt bonds break

and a new set of hydrogen bonds form

The interactions between the subunits areweaker in oxyhemoglobin than in

deoxyhemoglobin


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Methemoglobin

The heme iron is ferric rather than ferrous Can neither bind nor transport O2

Normally, the enzyme methemoglobin reductasereduces the Fe3+of methemoglobin to Fe2+

Methemoglobin can arise by oxidation of Fe2+to

Fe3+as a side effect of agents such as

sulfonamides, from hereditary hemoglobin M, orconsequent to reduced activity of the enzyme

methemoglobin reductase


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Erythrocytes can only generate adenosine

triphosphate (ATP) by glycolysis

The ATP is used for:

ion transport across the cell membrane (primarilyNa+, K+, and Ca2+)

the phosphorylation of membrane proteins

the priming reactions of glycolysis

Erythrocyte glycolysis also uses the

Rapaport-Luebering shunt to generate 2,3-

bisphosphoglycerate (2,3-BPG).


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The Respiratory Burst

When neutrophils and other phagocytic cellsengulf bacteria, they exhibit a rapid increase

in oxygen consumption known as the

respiratory burst

This phenomenon reflects the rapid utilization

of oxygen and production from it of large

amounts of reactive derivatives, such as

O2, H2O2, OH, and OCl(hypochlorite

ion)

Some of these products are potent icrobicidal

agents.


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The mutated

hemoglobin tends to

aggregate in the

deoxygenated form

This leads to sickle-

shaped distortion of the

erythrocytes anddisturbances

of O2 transport (sickle-

cell anemia)


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(4) biokimia sistem hematologi english

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