Materi Kul Biokimia Darah.blok 1.5. Des 2014

7/24/2019 Materi Kul Biokimia Darah.blok 1.5. Des 2014

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THE BLOODHAS MANY

FUNCTIONS

Biochemistry Department


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SPECIAL TOPICS

PLASMA PROTEINS ANDIMMUNO-GLOBULINS

RED AND WHITE BLOODCELL

HEMOSTASIS ANDTHROMBOSIS


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*Functions of Blood

Blood performs anumber of functions

dealing with:

Substance distributionRegulation of bloodlevels of particular

substancesBody protection


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*Disti!utionBloo

d

tra

nspor

ts:

Oxygen from the lungs andnutrients from the

digestive tract

Metabolic wastes from

cells to the lungs andkidneys for elimination

ormones from endocrine

glands to target organs


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*R"#ul$tion

Blood maintains:

!ppropriate body temperature byabsorbing and distributing heat

"ormal p in body tissues usingbuffer systems

!de#uate fluid volume in thecirculatory system


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*O%"%i"& of Blood Cicul$tion

Blood leaves theheart via arteries

that branchrepeatedly until

they becomecapillaries

Oxygen (O)* andnutrients diffuseacross capillarywalls and enter

tissues

'arbon dioxide('O)* and wastes

move from tissuesinto the blood


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*O%"%i"& of Blood Cicul$tion

Oxygen+deficient blood

leaves the capillaries andflows in veins to the heart

,his blood flows to thelungs where it releases

'O)and picks up O)

,he oxygen+rich bloodreturns to the heart


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*P'(sic$l C'$$ct"istics $nd )olu*"


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*Blood )olu*"


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*Co*+on"nts of W'ol" Blood

Figure 1

Withdraw blood and

place in tube1 2 Centrifuge

Plasma

(55% of whole blood)

Formed

elements

Buff coat!leu"occtes and platelets

(#1% of whole blood)

$rthroctes

(5% of whole blood)


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*Blood

Figure 10.12


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*Co*+osition of Blood


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*Co*+osition of Blood


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*Blood Pl$s*$


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*Pl$s*$


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*Ot'" co*+on"nts of +l$s*$


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*Fo*"d

"l"*"nts


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*Fo*"d El"*"nts


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*H"*o+oi"sis ,H"*$to+oi"sis


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*An Erythrocyte (RBC)


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* Erythrocyte Membrane Composition

http://www.ruf.rice.edu/~bioslabs/studies/sds-page/rbcmembrane.html

f l bi


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Structure of Hemoglobin

Red Blood Cells


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Red Blood Cells Found in higher concentration in ma

than in emale !la"ma

Biconca#e di"c"$ anucleate$e""entiall% no organelle"

&la"ma mem'rane contain" spectrina !rotein that gi#e" them (e)i'ilit%

Structural characteri"tic" contri'uteit" ga" tran"!ort unction

Biconca#e "ha!e that ha" a huge"urace area relati#e to #olume

Di"counting *ater content$er%throc%te" are more than +,-hemoglo'in

AT& i" generated anaero'icall%$ "the er%throc%te" do not con"umethe o)%genthe% tran"!ort. no

mitochondria/

Erythrocyte Function


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Erythrocyte Function

Er%throc%te" are dedicated to re"!irator% ga"tran"!ort

Hemoglo'in re#er"i'l% 'ind" *ith o)%gen and mo"to)%gen in the 'lood i" 'ound to hemoglo'in

Hb + O2 HbO

2

For*ard reaction occur" in the !ulmonar%ca!illarie"

0e#er"e reaction occur" in the "%"temic ca!illarie"

Hemoglo'in i" com!o"ed o the !rotein glo'in$ madeu! o t*o al!ha and t*o 'eta chain"$ each 'ound toa heme grou!

Each heme grou! 'ear" an atom o iron$ *hich can

Fate and De"truction o


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Fate and De"truction oEr%throc%te"

Hb Conservation and Recycling


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Hb Conservation and Recycling

Iron


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Erythropoiesis


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y p

A hemocytoblast transforms into a committed cell called the proerythro-

blast roerythroblasts develop into early erythroblasts !he developmental path"ay consists of three phases

hase # $ ribosome synthesis in early erythroblasts hase % $ hemoglobin accumulation in late erythroblasts and

normoblasts hase & $ e'ection of the nucleus from normoblasts "hen cell has

&() of the Hb it "ill ultimately have and formation of

reticulocytes Reticulocytes then become mature erythrocytes

Regulation and Reuirements for


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Regulation and Reuirements forErythropoiesis

Hormonal Control o


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Hormonal Control oEr%thro!oie"i"

Erythropoietin +echanism


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y p

Figure 1

&mbalance

'educes 2

leels

in blood

$rthropoietin

stimulates red bone

marrow

$nhanced

erthropoiesisincreases 'BC

count

*ormal blood o+gen leels ,timulus! -po+ia due todecreased 'BC count.

decreased aailabilit of 2to

blood. or increased tissue

demands for 2

&mbalance

,tart

/idne (and lier to a

smaller e+tent) releases

erthropoietin

&ncreases

20carring

abilit of blood

Dietar% 0e1uirement" o


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% 1Er%thro!oie"i"

H lbiG dG P d


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http://www.mun.ca/biology/desmid/brian/BIOL3530/DB_Ch09/fig9_24.jpg

Hemoglobin Genes and Gene Products

Hemoglobin Genes and Gene Products


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http://www.blackwellpublishing.com/korfgenetics/figure.asp?chap=13&fig=Fig13-1http://www.embryology.ch/anglais/qblood/blut03.html

g

HbF: 2and 2 HbA1: 2and 2

HbA2: 2and 2HbE: 2and 2

Umbilical vesicle

liver

spleen

Bone marrow

H lbiS Ch


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Hemoglobin Structure Changes

http://www.mfi.ku.dk/PPaulev/chapter8/images/8-3.jpg


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Depends on pH ([H+]), CO2, BPG (DPG), Temp

Factors Affecting Binding of O2

pH down

BPG or T up; right shift

pH up

BPG or T down; leftshift


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Erythrocyte metabolism


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Erythrocyte metabolism

Red Blood Cell Metabolism


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Metabolism These pathways are essential or o!ygen transport and

maintaining the physical characteristics o the RBC. $mbden0eerhof glcoltic pathwa

"enerates #0$ o energy needed by RBC%s

"lucose is metaboli&ed and generates two molecules o 'T( )energy*.

-e+ose monophosphate shunt Metaboli&es +,10$ o glucose.

-'(/ is end product

(rotects the RBC rom o!idatie inury.

Most common deect is deiciency o the en&yme glucose,,phosphate dehydrogenase (03P4)

3 the pathway is deicient4 intracellular o!idants can%t be neutrali&edand globin denatures then precipitates. The precipitates are reerredto as-ein6 bodies. )Must use supraital stain to isuali&e them.*



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ethemoglobin reductase pathwa Maintains iron in the errous )Fe2* state.

3n the absence o the en&yme )methemoglobin reductase*4

methemoglobin accumulates and it cannot carry o!ygen.

7eubering0'apaport shunt 'llows the RBC to regulate o!ygen transport during

conditions o hypo!ia or acid,base imbalance.

(ermits the accumulation o 245,(" which is essential

or maintaining normal o!ygen tension4 regulating

hemoglobin ainity


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E

rythrocyt

emetabo

lism


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E

rythrocyt

emetabo

lism

(entose phosphate pathway


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p p p y

'naerobic glycolysis and 245,B("


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g y y

245,B(" and hemoglobin,o!ygen binding


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eo!y/b ainity to bind 245,B(" is 100,oldhigher that that o 6!y/b

Binding o 245,B(" to /b decreases /b ainityto bind 627 right shit o the cure

2 mmol8l

9 mmol8l

mmol8l

/bsaturation

p62

tissues

lungs

:ungs

6nly a small decrease

o o!ygen loading

Tissues

;igniicant increase

o o!ygen unloading

/b o!ygen saturation and erythrocyte metabolism


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(hosphoructo


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lucose transporter!

integral membrane protein )12 membrane,spanning helices*

a channel or the glucose transport

insulin,independent transporter

Glycolysis in erythrocytes

1 ,ource of 89P :actate, the end product

Coer #0$ o energy re>uirement

2 enerate 2.:0bisphosphoglcerate (2.:0BP)

a maor reaction pathway or the consumption o glucose in erythrocytes the speciic binding o 245,B(" to deo!yhemoglobin decreases the o!ygen ainity o

hemoglobin and acilites o!ygen release in tissues


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2,3-bisphosphoglycerate


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8llosteric effector of haemoglobin!

binds to deo!yhaemoglobin )a central caity capable o binding 245,B("*

decreases haemoglobin?s 62ainity

Clinical aspects!

3n people with high,altitude adaptation or smo


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Glutathione$limination of -22and organic hdropero+ides


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2 2

1. Coactor or the glutathione pero!idase)remoes /262ormed inerythrocytes*

2. 3noled in ascorbic acid metabolism

5. (reents protein @;/ groups rom o!idi&ing and cross,lin


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"enerates -'(/ , reduction o glutathione )eliminates /262ormed in erythrocytes*

Clinical apect!

lucose030phosphate dehdrogenase deficienc

Causes hemolytic anemia )decreased production o -'(/ , reduced protection

against o!idatie stress , haemoglobin o!idation and /ein& bodies ormation4

membrane lipid pero!idation and hemolysis*

/emolytic crises are eocated by drugs )prima>uine4 sulphonamide antibiotics* and

oods )broad beans*

The most common en&yme deiciency disease in the world )100 million people*


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6!yhaemoglobin62

Superoxide dismutase


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/aemoglobin

MethaemoglobinMethaemoglobin reductase

;upero!ideSuperoxide dismutase

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Catalase

62A/

Glutathione peroxidase

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";/

";;"

Glutathione reductase

-'(/

-'(A(entose phosphate

pathway

";/,reduced orm ";;",o!idi&ed orm o glutathione

Haemoglobin autoxidation 5$ o the haemoglobin undergoes o!idation eery day a constant lu! o 62

D,


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2

-em 0 Fe2;0 2 -em 0 Fe:; 0 2


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a high concentration in erythrocytes

accelerates the dismutation 62D,to /262

H2!2 remo$e

1 Catalase

2 lutathione pero+idase

%& 'atalase

a erric haem group bound to the actie site

catalyses decomposition o /2

62

to water and o!ygen

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2& Glutathione peroxidase

remoes / 6 by coupling its reduction to / 6 with o!idation o reduced glutathione


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remoes /262by coupling its reduction to /26 with o!idation o reduced glutathione)";/*

/262A2";/";;"A2/26

lutathione reductase reduces o!idi&ed glutathione bac< to reduced

";;"A-'(/A/A 2";/A-'(A

-'(/, the pentose phosphate pathway )glucose,,phosphate dehydrogenase*

Cooperation of glutathione pero+idase and catalase

The concentration o /262 is raised, catalase becomes more important )high =m or/262*

(ow-molecular mass antioxidants

= tocopherol (itamin $)


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=0tocopherol (itamin $)

(resent in the erythrocyte membrane

(reents lipid pero!idation )chain,brea


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R6; H molecules4 atoms or ions capable to react aidly with lipids )membranes*4

proteins4 nucleic acids and impair their structure and unctionRadicals R6; with an unpaired electron

3ncreased R6; production and8or decreased degradation H o!idatie stress

3mportant reactions, ;upero!ide generation 62A e

,7 62D,

, Fenton reaction Fe2AA /2 62 7 Fe5AA 6/ A 6/D,

, /aber,Ieiss reaction 62D,A /262 7 6/ A 6/

D,

, ;upero!iddismutase );6* 62D, A62

D, 7 /262 A 62, Catalase )C'T* 2 /262 72 /26 A 62, "lutathionpero!idase )"(J* 2 ";/ A R,6,6/ 7 ";;" A /26 A R6/

2 ";/ A /2627 ";;" A 2 /26

R6; in the erythrocytes


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/igh 62 content

' transition metal Fe )2A75A*4 contained in /b

/b autoo!idation

/emFe2AA 62 K )/em Fe2AL62K /emFe

5AL 62D,* K /emFe5AA K 62

D,

Regeneration o /b methemoglobinreductase

Erythrocytes are rich in antio!idant en&ymes ;64 "(J4 C'T =ey role o glutathione ),glutamyl,cysteinyl,glycin4 ";/*

Reaction o "(J

irect reaction with molecules modiied by R6;

";/ regeneration by glutathionreductase

";;" A -'(/ A /A7 2 ";/ A -'(A

(entose phosphate pathway is the source o -'(/ A /A

-'(/ and antio!idant protection


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-'(/ A /A is produced in a reaction cataly&ed by glucose,,

phosphatedehydrogenase )"(*

"( deiciency (robably the most re>uent en&ymopathy )L100 million people4 500 genetic

ariants o the en&yme*

Fre>uent in mediterranean countries4 tropical 'rica4 'sia

Results in hemolytic anemia4 worsened by some oods )broad beans* or drugswhich act as o!idants

/emolysis is caused by o!idatie impairment o membrane lipids )pero!idation*4proteins )o!idation o thiol groups to disulides*

Methemoglobinemia


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'bout 5$ o /b is conerted to met/b and bac< in 29 hours4 but

met/b concentration is normally ery low Causes o increased met/b concentration

3nherited deiciency o methemoglobinreductase 3ncreased susceptibility o abnormal /b ariants to autoo!idation )/bM4

/b; , sic


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The blue people of Troublesome Creek. Science 1982. lustrace !alt Spit"miller.

Erythrocyte ,isorders


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y y

Anemia .nsufficient Erythrocytes


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Anemia2 Decrea"ed Hemoglo'inContent


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Content

Anemia Abnormal Hemoglobin


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Anemia Abnormal Hemoglobin

olycythemia


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/hite Blood Cells


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Neutrophils 0polys12 +31s afterleaving bone marro"2 stay incirculation #4-#% hours then move into


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other tissues5 Become motile2phagocyti6e bacteria2 antigen-antibodycomple7es and other foreign matter5Secrete lyso6yme5 8ast #-% days5 9:-;:) of total /BC

Eosinophils5 8eave circulation and

enter tissues during inflammatoryresponse5 revalent in allergicreactions5 Release chemicals that helpdestroy tape"orms2 flu


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Responsible for antibody production5 Studiede7tensively "ith the immune system5 %4-%:) of

total

Basophils least common5 8eave circulation andmigrate through tissues2 play a role in bothinflammatory response and allergic reactions5roduce histamine and heparin5 45:-#) of total

/BC

Monocytes remain in circulation for & days2 leavecirculation and become macrophages5 hagocyticcells5 Can brea< do"n antigens and present them to

lymphocytes for recognition5 &-9) of total


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*Poduction of L"u.oc(t"s


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*Fo*$tion of L"u.oc(t"

*Fo*$tion of L"u.oc(t"s


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Figure 17


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*L"u.oc(t"s Disod"s/ L"u."*i$s


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*L"u."*i$


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latelets


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*Pl$t"l"ts

Genesis of Platelets


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Figure 17


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*Pl$t"l"t Plu# Fo*$tion


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*Co$#ul$tion


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*Co$#ul$tion

Figure 17.

*D"t$il"dE t f


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E%"nts ofCo$#ul$tion

Figure 17.

* Co$#ul$tion P'$s" 0/ T&o P$t'&$(s toPot'o*!in Acti%$to


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*Co$#ul$tion P'$s" 1/ P$t'&$( toT'o*!in

* Co$#ul$tion P'$s" 2/ Co**on P$t'&$(s to t'"Fi!in M"s'


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*Clot R"t$ction $nd R"+$i


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*F$ctos Li*itin# ClotGo&t' o Fo*$tion

In'i!ition of Clottin# F$ctos


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F$ctos P"%"ntin# Und"si$!l" Clottin#


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* H"*ost$sis Disod"s/T'o*!o"*!ol(tic Conditions


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*P"%"ntion of Und"si$!l" Clots


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*H"*ost$sis Disod"s


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*H"*ost$sis Disod"s/ Bl""din# Disod"s


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Blood =rouping


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AB> Blood =roups


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Agglutination Reaction


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!ransfusion


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Rh Blood =roup


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Erythroblastosis Fetalis


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,iagnostic Blood !ests

ype and Crossmatch: determination of ABO


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and Rh blood types. Red cells tested againstantibodies

Complete Blood Count

Red Blood Count: number of RBCs/ microliter ofblood

Hemoglobin Measurement: grams ofhemoglobin/!! m" of blood. #or a male$ %&'$female (&) g/!! m"

Hematocrit Measurement: percent of blood thatis RBCs

*hite Blood Cell Count: +$!!!&!$!!! /microliterof blood

Hematocrit


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Glycosylated haemoglobin Hb)%#

ormed by hemoglobinNs e!posure to high plasma leels o glucose non,en&ymatic glycolysation )glycation*, sugar bonding to a protein normal leel /b'1, +$ a buildup o /b'1, increased glucose concentration

the /b'1leel is proportional to aerage blood glucose concentration oer preious


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1 g g

weeuantities othese glycated hemoglobins are noted )patients monitoring*

Sugar C/6 A -/2C/2#rotein

Sugar C/ - C/2#rotein

Sugar C/2 -/ C/2 #rotein

Schiff base

Gl$cos$lated protein

%madori reaction


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*Su**$( of Fo*"dEl"*"nts

Table 1


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*Su**$( of Fo*"dEl"*"nts

Table 1

Materi Kul Biokimia Darah.blok 1.5. Des 2014

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