kuliah 4. metab-porfirin ugik edited
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7/24/2019 Kuliah 4. Metab-porfirin UGIK Edited
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dr. SUGIYANTA, M.KedLABORATORIUM BIOKIMIA
FKUJ
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Ikterus / Jaundice
Di masyarakat dikenal penyakit kuning
Di klinik dibedakan berdasarkanpenyebab timbulnya ikterus
Diagnosa klinis Anamnese! pemeriksaan "sik!
Laboratorium dalam dara#! $ae%es! urinedan tin&a
Ikterus merupakan bagian darimetabolisme
'or"rin dalam tubu# (
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'ORFIRI)
'or"rin adala# *enya+a siklik gabungan dari ,%in%in pirol dan &embatan metenil - ./0 12
*3)4A5A I)I DA'AT B3RIKATA)D3)6A) LO6AM Fe ATAU Mg
Fe heme
Mg : Kh!r!"i
heme # "r!tein hem!"r!tein
c!nt!h : $%
Ikatan &!r'rin # !gam Meta!"!r'rin
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03MO'ROT3I) TUBU0
03MO6LOBI) - 0b 2 TRA)*'ORTA*I O78 /O7
MIO6LOBI) 'ADA OTOT - MU*/L3 2
*ITOKROM TRA)*'ORTA*I 3L3KTRO) 8'ROTO)
*ITOKROM ',9: U)TUK ;3)OBIOTI/ 8
0IDROK*I LA*I RA/U)(
KATALA*3 3)
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*TRUKTUR 'ORFIRI)
CH
HC
HC
CH
Fe
N
PIROL
PORFIN
( C10H14N4)
I
II
III
IV
N
N
N
N
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STRUKTUR PORFIRIN
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12
3
4
5 6
8
GUGUS SAMPING ( Menentukan Nama Senyawat tsb )
AS!"A" ( A ) # CH$%COOH
PROPIONA" ( P ) # CH$%CH$%COOH
M!"IL ( M ) # CH&
'INIL (' ) # CHCH
7
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A P
A
P
A P
A
P
UROPORFIRIN I
A P
A
P
A P
P
A
UROPORFIRIN III
M P
M
P
M P
M
P
OPROPORFIRIN I
M P
M
M P
P
M
OPROPORFIRIN III
P
P
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*IFAT.*IFAT 'ORFIRI):
=( AB*OR'*I *'3KTRUM 4A)6 K0A*
'ADA 'A)JA)6 63LOMBA)6 ,:: nm
7( *3MUA J3)I* 'ORFIRI) B3R5AR)A!
M3)43RA' *'3/TRUM /A0A4A'ALI)6 TAJAM 'ADA > ,:: nm?( M3MB3RIKA) FLUOR3)*3)*IM3RA0
'ADA *I)AR U(@(
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BIO*I)T3*I* 'ORFIRI) DA) 03M3
"!R*A+I +I S!MUA S!L ( R!S ), "!RU"AMA +I
SUMSUNG "ULANG
PROS!S R!ASI "!R*A+I +I MI"OON +RIA
+AN SI"OPLASMA-AHAN -AUN.A #
. ASAM AMINO GLISIN
. SUSINIL % /A . / enm PIRI+OSAL FOSFA".
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*UK*I)IL.KoA
COOH
CH2
C=O
S-CoA
+
6LI*I)
H
H-C-NH2
COOH
COOH
CH2
C=O
C-NH2
COOH'iridoksal$os$at
ALA-SINTASE
KoA-SH
.AMI)O..K3TO ADI'AT
COOH
CH2
CH
2
C=O
C-NH2
H
.AMI)O L3@ULI)A-ALA2
ALA-SINTASE
CO2
COOH
CH2
CH2
C=O
CH2
NH2
COOH
CH2
CH2
O = C
H-C-H
H
NH
7 MOL( .AMI)O
COOH
CH2
C
C
COOH
CH2
CH2
C
C CH
2NH
NH2
'ORFOBILI)O63) - prekursorpertama
ALA-
DEHIDRATASE
2 H2O
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0OO/ /OO0
A 07/ /07 '
/07
/ /
/ /0
07/ )
)07 0, MOL( 'ORFOBILI)O63)
UROPORFIRINOGEN I
SINTASE
, )0?
0IDROK*I M3TIL BILA)
- T3TRA 'IROL LI)3AR2
A ' A '
07
/
/
07
' A ' A
)
)
) )
/07/07
A ' A'
07
/))
)) /
07
/07/07
A ' 'AURO'ORFIRI)O63) I URO'ORFIRI)O63) III
OK*IDA*I*'O)TA)
UROPORFIRINOGENI SINTASE &
UROPORFIRINOGENIII KOSINTASE
I II I
II
I@ III I@
III
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I I
I@ II I@II
III III
I I
I@ II I@
II
III III
URO'ORFIRI)O63)
I KO'RO'ORFIRI)O63)I
UROPORFIRINOG!N III KO'RO'ORFIRI)O63) III
A '
'A
A'
' A
, /O7
UROPORFIRINOGEN
DEKARBOKSILASE
, /O7
A '
A
'
'
M
M
M
M
'
M
MM
M
A
P
AP
P P
P
P
P
P
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A0A'A) *I)T3*I* D3RI@AT 'ORFIRI) dari 'ORFOBILI)O63
'ORFOBILI)O63)
0IDROK*IM3TILBILA)
URO'ORFIRI)O63) I*I)TA*3
UROPORFIRINOGEN
III
UROPORFI
RIN III
6 H
CAHAYA
URO'ORFIRI)O63) III KO*I)TA*3
URO'ORFIRI)O63) I *I)TA*3
SPONTAN
UROPORFIRINOGEN
UROPORFIRIN
CAHAYA
6 H
KOPROPOR KOPROPORFIRINO
FIRIN III GEN III
6 H
CAHAYA
KOPROPORFI- KOPORPOR-
RINOGEN I FIRIN I
6 H4 CO2
4 CO2
UROPORFIRINOGEN
-DEKARBOKSILASE
PROTOPORFIRINOGEN III
PROTOPORFIRIN III
H E M E
Fe++
KOPROPORFIRINO-
GEN OKSIDASE
PROTOPORFIRINOGEN
OKSIDASE
FERROKELATASE
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'OR'04RI) BIO*4)T03*I* -03M32'OR'04RI) BIO*4)T03*I* -03M32
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D3/ARBO;ILATIO) OFURO'OR')4RI)O63)
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R!ASI SIN"!SIS PORFIRIN # /A
1 GLISIN 2 SUSINIL%/A ASAM AMINO %!"O A+IPA"
ALA-Sintase CO$
ASAM AMINO %!"O A+IPA" ASAM %AMINO L!'ULINA"
ALA-Sintase ( AML!' ALA )
$ H$O
2. $ MOL AML!' PORFO-ILINOG!N ( P-G )
Amlev. Dehidrogenase ( P3a at e3tama 5a3 3/6 )
& 4 M/6 PORFO-ILINOG!N HI+ROSI M!"IL -ILAN
- 'B6 2 Uroporfirinogen I sintase
SPONTAN UROPORFIRINOG!N I
4 HI+ROSI M!"IL -ILAN
Uroporfirinogen I sintase & Uroporfirinogen III kosintase
UROPORFIRINOG!N III
7 UROPORFIRINOG!N I UROPORFIRINOG!N III
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7 UROPORFIRINOG!N I UROPORFIRINOG!N III
CO$ Uroporfirinogen dekarboksilase CO$
OPROPORFIRINOG!N I OPROPORFIRINOG!N III
8 Koproporfirinogen oksidase CO2
PRO"OPORFIRINOG!N I9
: Protoporfrinogen oksidse O2
PROTOPORFIRIN III
Fe22
Ferrokelatase H ! M ! ( H!M )
GLO-IN
H!MOGLO-INR!ASI 1 "!R*A+I +I+ALAM MI"OON+RIA
R!ASI $ s;5 7 "!R*A+I +I+ALAM SI"OPLASMA
R!ASI 8 5an : "!R*A+I +I+ALAM MI"OON+RIA
ALA SIN"AS! M!RUPAAN !N
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'3)63)DALIA) *I)T3*I* 03MO6LOBI) SUSINIL%/A 2 GLISIN
1 ALA Sintase
% AMINO L!'ULINA"
2 ALA 5e=53atase
PORFO-ILINOG!N
& Uroporfirinogen I sintase
HI+ROSI M!"IL -ILAN
4 Uroporfirinogen III kosintase
UROPORFIRINOG!N III UROPORFIRINOOG!N I
7 Uroporfirinogen dekarboksilase
OPROPORFIRINOG!N III
8 Koproporfirinogen oksidase
PRO"OPORFIRINOG!N I9
: rotoporfirinogen oksidase
PRO"OPORFIRIN III
> Fe Ferrokelatase
H ! M ! H!MOGLO-INA'OR3'R3*OR
GEN OPERATOR
*intesis 0eme di Mitokondria*intesis 0eme di Mitokondria
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*intesis 0eme di Mitokondria*intesis 0eme di Mitokondria
22
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ALA sintase -ALA*2 ALA sintase -ALA*2 Jenis (
A)AS* di i+er A)AS eritr!id
-eguasi sintesis A)AS* di i+er :
Meningkat dere"resi %ia kadar heme turun
&enurunan kadar heme da"at di"icu !ehsen0a1a kimia asing 2en!%i!tics mis.3%atan, %ahan tam%ahan daam makanan,
"!utan !.k meta%!ismen0a memerukansit!kr!m &456 hem!"r!tein
Menurun re"resi "em%erian guk!sa,hematin
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'ORFIRIA*3K3LOM'OK '3)4AKIT K3TURU)A) 8 03R3DIT3R 4A)6B3R0UBU)6A) D3)6A) *I)T3*I* 03M(
*3BAB K3LAI)A) *I)T3*I* - MUTA*I 63)3 2 3)
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G7JA)A &3-FI-IA &3-FI-IA 8IK)ASIFIKASIKAN S79AGAI GANNGUAN
$7&ATIK ATAU 7-IT-3&37TIK, 8IS79A9AKAN&ASI7N T7-&A&A- 39AT, A)K3$3) K7NA A$AYAMATA$A-I 87NGAN G7JA)A :
'ORFIRIA 03'ATIK
N7U-3;IS7-A) S7&7-TI MUA), MUNTA$ ,SAKIT &7-UT, TAKIKA-8I, $I&7-T7NSI , N7U
-3&ATI &7-IF7- 8AN G7JA)A M7NTA) $A)U
SINASI, 7MAS , K7JANG
&3-FI-IA 7-IT-3&37TIK : GANGGUAN F3T3S7NSITI;ITAS. KU)IT &7KA
T7-$A8A& A$AYA
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'OR'04RIAD)A MUTATIO)
-63)3 OF T03 3)
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TAB3L 'ORFIRIA
*!NIS +!FISI!NSI !N
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KATABOLI*M3 03M3S!"IAP 1$0 HARI !RI"ROSI" ; Hb +IP!CAH
!RI"ROSI" H!MOGLO-IN H!M! Fe222 2 GLO-IN 2 -ILI%
RU-IN
P!M!CAHAN "!R*A+I +I S!L%S!L R!S ( H!PAR, LI!N @ SUMSUM
"ULANG ), OL!H S!L%S!L MAROFAG
PA+A ORANG +!ASA, :0 B, S!"IAP HARI 8 GRAM Hb +IP!CAH
1 GRAM Hb M!NGHASILAN &7 MG -ILIRU-IN "IAP HARI +IHA%
SILAN $70 ? &70 MG -ILIRU-IN
DI R 3 *
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DI R 3 * !RI "UA ; RUSA +IMAAN OL!H MAROFAG
!RI Hb H!M! 2 GLO-IN
GLO-IN ASAM AMINO
HAP"OGLO-IN
H!M +I OSI+ASI OL!H SIS"!M H!MOSIG!NAS!, M!NGHASILAN #
> Fe22 Fe++ + ( H!MIN )
> -ILI'!R+IN ( !"!#A I#$L LI%"A# !"#'UKA (
Fe2226eas "RANSF!RIN H!PAR+ARAH
-ILI'!R+IN +I OSI+ASI -ILIRU-IN +ARAH
( Bmen =Dau ) ( Bmen kunnB me3a= )
SIFA" -ILIRU-IN INI # % SANGA" "OSI "A LARU" +ALAM AIR, "!"API
+APA" M!N!M-US *ARINGAN O"A
-ILIRU-IN 2 AL-UMIN -ILIRU-IN AL-UMIN +ARAH H!PAR
DI 03'AR
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DI 03'AR
ALBUMI) DIL3'A*KA)! DI6A)TI D3)6A) LIGANDIN!
BILIRUBI).LI6A)DI) MA*UK K3 *3L 0A'ATO*IT! K3MUDIA) DI
KO)JU.6A*I.KA) D3)6A) A*AM 6LUKORO)AT OL30 3)
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-ILIRU-IN +IGLUORONI+A +IS!R!SI ! +ALAM !MP!+U, S!CARA
A"IF +I"!RUSAN ! USUS
DI U*U*
+I IL!UM @ COLON, ON*UGASI +IL!PASAN
-ILIRU-IN +I R!+USI OL!H -A"!RI USUS menDa5
URO-ILINOG!N ; S"!RO-ILINOG!N
UROBILI)O63) 8
*T3RBILI)O63)
*ebagian di *3KR3*I M3LALUIF3*3*
*ebagian di R3AB*OR'*I MA*UK K303'AR
sebaBan 5 OSI+ASI M!N*A+I
-ILIRU-IN LAGI ON*UGASI
6aB +AN S!"!RUSN.A
*ebagian lagi '3R3DARA) DARA0 03'AR'3R3DARA) DARA0 *I*T3MIK K3 6I)JAL
K3 URI)3(
*IKLU* 3)T3RO03'ATIK
F!"#$"%&'KATABOLISME & EKSKRESI HEME
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USUS
MU*/L3
OTAK
03'AR
R 3 *
GINAL
SDM
F!"#$"%&'
HbGLOBULIN
HEME
BILIVERDIN
Fe+++Hee!O"#$%e&'#e
BILIRUBINALBUMIN
BILIRUBIN
LIGANDIN
BILIRUBIN
!GLUKURONAT
UDP!G)*"*+,&$)
T+'-e+'#eBILI!GLUK
ENZ. FLORA USUS
STERKOBLNGSTERKOBLNG
*T3RKOBILI)
UROBILI
STERKOBILIN
-73KSI8ASI
BILI!GLUK
SIRKULASI
ENTERO!HEPATIK
KATABOLISME & EKSKRESI HEME
V. PORTAS'*'
Ee0*
ALUR PIGMEN
KATABOLI*M3 0b DA) 3K*KR3*I
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KATABOLI*M3 0b DA) 3K*KR3*IBILIRUBI)
R 3 *
03'A
R
U*U*
/OLO)
GINAL
0b 03M3 C6LOBI)
BILIVERDIN
A(A
0A'TO6LOBI)
BILIRUBI)
ALB
UMI)
-ILIRU-IN-ILI
+IGLU
)ASAM GLUKORONAT
BILI(DI6LU
K
BILI. UROBILI8*
T3RKOBILI)O6
3)
R3D
URO-ILINOG!N
UROBILI)O63
)
UROBILI)O63)
UROBILI)
-URI)3 2
*T3RKOBILI) - F3*3* 2
6I)JAL
BILIRUBI)UDP GlukoronilTransferase
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0I'3RBILIRUBI)3MIAKA8A- 9I)I-U9IN 8A-A$
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&en0e%a% :
*. &r!duksi %iiru%in ugasi ugasi aa : >aundice / ikterus
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Skema
P3/sesatab/6s
me
-63ubn
-ese3ta-ebe3aa
Penyebab
*aun5Ee
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0I'3RBILIRUBI)3MIA B3RDA*AR J3)I*
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0I'3RBILIRUBI)3MIA B3RDA*AR J3)I*BILIRUBI))4A :I( U)/O)JU6AT3D 04'3RBILIRUBI)3MIA
I.*. A. IK!"#US %"$%A!$#U+ FISI$L$)IKU+ ,
-!RSIFA" S!M!N"ARA
CAUSA # SIS"!M ON*UGASI H!PAR MASIH -!LUM
S!MPURNA, A"I'I"AS !N
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*.1 . SI%D#$+A #I)L"# %A A# !I" II ,
H!R!+I"!R
!N
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II( /O)JU6AT3D 04'3RBILIRUBI)3MIA
CON*UGA"!+ -ILIRU-IN LARU" +ALAM AIR +APA"
+I!LUARAN M!LALUI URIN! ARNA URIN! S! ?
P!R"I !MP!+U CHOLURIC *AUN+IC!
II1 SIN+ROMA +U-IN *OHNSON ( I"!RUS I+IOPA"I ) #
SIS"!M !SR!SI !MP!+U "I+A S!MPURNA
II$ SUM-A"AN SALURAN !MP!+U ( IN"RA @ !S"RA H!PA"AL )
'3MBA6IA) B3RDA*AR K3ADAA) KLI)I*
( N!ONA"ORUM *AUN+IC! I"!RUS N!ONA"ORUM
$ HA!MOL."IC *AUN+IC! I"!RUS H!MOLI"I
& H!PA"IC *AUN+IC! I"!RUS H!PA"I
4 O-S"RUC"I'! *AUN+IC! I"!RUS SUM-A"AN
S79A9 S79A9 9I)I-U9IN 8A-A$ M7NINGKAT
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S79A9@S79A9 9I)I-U9IN 8A-A$ M7NINGKAT:
1 P!M!CAHAN H!MOGLO-IN ; H!M M!NINGA" #
MISAL # MALARIA
!LAINAN S!L +ARAH M!RAH HbF
LA- # -ILIRU-IN AL-UMIN ( FR!! -ILI -ILI IN+IR! )
URO-ILIN URIN! S"!RO-ILIN F!C!S
-ILIRU-IN URIN! (%)
$ !MAMPUAN ON*UGASI H!PAR M!NURUN #
MISALN.A PA+A -A.I PR!MA"UR SIN"!SIS U+P%GLUORONIL
"RANSF!RAS! URANG
LA- # % -ILIRU-IN IN+IR!
% S"!RO-ILIN F!S!S 5an URO-ILIN URIN! IKT3RU* )3O)ATORUM '04*IOLO6I/UM
-. -ILA URANG +ARI 1 MINGGU -ILIRU-INN.A SU+AH HILANG
% -ILA -ILIRU-IN L!-IH +ARI 1 MINGGU - A H A . A #
!NC!PHALOPA"HIA !RN IC"!RUS
& SUM-A"AN SALURAN !MP!+U
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& SUM-A"AN SALURAN !MP!+U #
> AR!NA -A"U, CACING, CIRRHOSIS H!PA"IS
> LA- # -ILI +IR! S"!RO-ILIN F!S!S A"AU (%)
-ILI URIN! (2) URO-ILIN URIN! A"AU (%)
4 !RUSAAN S!L H!PAR #
> "!R*A+I PA+A H!PA"I"IS
> S!L RUSA ; SAI" ISI S!L *A+I -OCOR !LUAR
MASU ! SINUSOI+ H!PAR ! P!R!+ARAN +ARAH
SIS"!MI
LA- # -ILIRU-IN +IR! -ILIRU-IN URIN!
(2)
URO-ILIN URIN! S"!RO-ILIN
A+AR NORMAL -ILIRU-IN +ALAM +ARAH #
-ILIRU-IN +IR! # 0,1 % 0,4 mB;56
-ILIRU-IN IN+IR! # 0,$ % 0,: mB;56
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DATA LABORATORIUM IKT3RU*
J3)I* IKT3RU* DARA0 URI)3 FA3/3*
NEONATORU% FIS BIL( DIR3K ) UROBILI) E *T3RKOBILI) E
BIL( I)DIR3K BILIRUBI) -.2
$E%OLITIKU% BIL( DIR3K ) UROBILI) *T3RKOBILI) BIL( I)DIR3K )8 BILIRUBI) -.2 *T3RKOBILI)
OBSTRUKSI BIL(DIR3K UROBILI) E *T3RKOBILI) E
BIL(I)DIR3K ) BILIRUBI) -C2
$EPATIKU% BIL( DIR3K UROBIL E8 )8 *T3RKOBILI) E
BIL(I)DIR3K BILIRUBI) -C2
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