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Chapter 16 

Hemal Biochemistry

The biochemistry department of SYMC

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Quaternary Structure of hemoglobin

• O transporter in!BC"

• #

subunits， $achsubunit containsone heme group"

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%1 Heme Synthesis

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Sites&

Mitochondria and cytosol

'recursors&

(lycine) succinyl Co*) +e,

ferriion

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1" Synthetic path-ay of heme

.1/ The formation of 0amino leulinic acid.*2*/

+

HSCoA + CO2

  *2* synthase

.pyrido3alphosphate/

4n the mitochondria

COOH

HC

CH

C56SCo*

O

CH7H

COOH

COOH

HC

CH

C

CH7H

O

levulinic=Acetyl propionic acid 乙酰丙

ALA synthase is the key enzyme 

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./ The formation of porphobilinogen .'B(/

*2*dehydratase

2H2O

4n the cytosol

7H

OH

O

OH

O

7H

COOH

CH

CH

C

C

7

O

H H

H H

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.8/ The formation of uroporphyrinogen Ⅲ.9'( / and coproporphyrinogenⅢ Ⅲ.C'( /Ⅲ

#: 'orphobilinogen2inear

tetrapyrrol

9'(ⅢC'(Ⅲ

;eaminase

9'( Ⅲisomerase

9'(Ⅲ

decarbo3ylase

4n the cytosol

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'rotoporphyrinogen Ⅸ

'rotoporphyrin

ⅨHeme

ferrochelatase

.#/ The formation of heme

C'(Ⅲo3idase

C'(Ⅲ

'rotopor0phyrinogen

Ⅸo3idase

4n the mitochondria

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Heme

'rotoporphyrinⅨ

'rotoporphyrinogen

Ⅸ C'(Ⅲ9'(Ⅲ

2ineartetrapyrrol

PBG

(ly

succinyl Co*

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.1/ *2* synthase

•!ate0limiting en

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.8/ $rythropoietin .$'O/ can increase

synthesis of heme and hemoglobins"

./ *2* dehydrase and ferrochelatase

  4nhibited by heme) and heay metals"

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%

Metabolism of Bile

'igment and >aundice

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bile pigment is the main catabolic

product of iron porphyrin compound in

the body) consisting of bilirubin)bilierdin) bilinogen and bilin"

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The source of bilirubin

The compounds inoling iron

prophyrin in the body are

hemoglobin) myoglobin) cytochrome)pero3idase) and catalase) etc"

1" +ormation and transport of

bilirubin

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+ormation of bilirubin

•  site

4n the microsome and cytosol of

mono=aryon0 macrophage system of

the lier) spleen) and bone marro-"

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7   7

77

HOOC

+e,

COOH

O

7*;'H,H,7*;',

CO+e8,

H7

H7

'

7

'

H7O   O

7*;'H,H,

7*;',

H7H7

''

H7O   OHH

heme

bili1erdin

bilirubin

heme o3ygenase

bili1erdin reductase

H7

¦Ä

¢ô   ¢ó

¢ò¢ñ

¦Ã

¦Â

¦Á

•  processKetoform enol form 

Reduce reduction

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The spatial structure of bilirubin

7

7 H

7

7

O

C

O

OO

H

C

O

H

H

OH

H

•  property

  hydrophobic

 

color 

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Transport of Bilirubin

•+orm of Transport

Bilirubin0albumin comple3

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" Bilirubin conersion in lier 

  9pta=e

 

Transport

Smooth $ndoplasmic reticulum

Combine -ith ligandin

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Con?ugation

Bilirubin

monoglucuronide

bilirubin

9;'9;'0glucuronyl

transferase

9;'(*

Bilirubin

diglucuronide

9;'(*

9;'9;'0glucuronyltransferase

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structure of bilirubin diglucuronide

H7

H7

H7

H7O O

HH

HCCH

CH

CO

O

CH

CO

OO

H

HO

H

H

OH

COOH

HH

OH

O

H

OH

HO

H

H

H

OH

H

COOH

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$3cretion

  Con?ugated bilirubin is secreted

into the bile and then e3creted into theintestine"

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Con?ugatedbilirubin

bilinogen

coliform

(lucuronic acid

Bilino3idi

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Bilinogen enterohepatic circulation

  4n the terminal ileum and large

intestine) a small fraction of the

bilinogens is reabsorbed and

ree3creted through the lier to

constitute the enterohepatic cycle ofbilinogen"

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Hb

globin

heme

7*;'H,H,

7*;',

bili1erdin

bilirubin

O

  HO

+e8,

,CO

7*;'H,H,

7*;',

bilirubin0albumincomple3

bilirubin

ligandinbilirubin0ligandin

comple3

bilirubin glucuronide

9;'(*

9;'$!

cytosol

li1er cellmono=aryon0macrophage cell blood

intestine

glucuronicacid

bilirubin

bilinogen

bilinogen .a little/

bilin

feces

=idneya smallfraction

a large fraction

bilinogenOO

bilin

urine

bilirubinglucuronide

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#" Serum bilirubin and ?aundice

•

 Con?ugated bilirubin is also calleddirect reacting bilirubin or

hepatobilirubin"

  Serum bilirubin

1～ 16 mol@l .A"1 ～ 1mg@dl/

• +ree bilirubin is also called indirect

reacting bilirubin or hemobilirubin"

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freebilirubin

 con?ugatedbilirubin

Binding -ith (lucuronicacid

no yes

!eacting -ith the dia

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>aundice

• Hemolytic .prehepatic/ ?aundice

•

Hepatocellular .hepatic/ ?aundice

• Obstructie .posthepatic/ ?aundice

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2aboratory results in patients -ith ?aundice

normal Hemolytic ?aundiceHepatocellular  ?aundice

Obstructie ?aundice

Serum bilirubin

total 1mg@dl 1mg@dl 1mg@dl 1mg@dl

direct AD A"Emg@dl ↑

indirect 1

9rine bile pigments

urobilirubin  F F , , , ,

urobilinogen * fe- ↑ uncertainty

urobilin * fe- ↑ uncertainty

Color of feces normal dar= Simple or normal Clay color 

↑↑ ↑

↑↑

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Hb

globin

heme

7*;'H,H,

7*;',

bili1erdin

bilirubin

O

  HO

+e8,

,CO

7*;'H,H,

7*;',

bilirubin0albumincomple3

bilirubin

ligandinbilirubin0ligandin

comple3

bilirubin glucuronide

9;'(*

9;'$!

cytosol

li1er cellmono=aryon0macrophage cell blood

intestine

glucuronicacid

bilirubin

bilinogen

bilinogen .a little/

bilin

feces

=idneya smallfraction

a large fraction

bilinogenOO

bilin

urine

bilirubinglucuronide