12/11/2014
METABOLISME PURIN DAN PIRIMIDIN
Ayu Puspitasari, ST, M.Si
Terdiri dari : 1.Basa 1. Basa Nitrogen Nitrogen 2.Gula 3.Fosfat
1
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12/11/2014
Nukleotida Nukleot ida TANP ANPA A fosfat = Nukleosida
Nukleotida
= nukleosida monofosfat/ nukleosida difosfat/
nukleosida trifosfat
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12/11/2014
Basa penyusun :
1. PURIN 2. PIRIMIDIN
Basa Basa Puri Purin n yang yang lain lain : •
Kafein (1,3,7-trimetil xantin)
•
Teobromin (3,7-dimetil (3,7- dimetil xantin )
•
Teofilin ( 1,3-dimetil xantin )
•
Dimetilaminadenin
•
7-metilguanin
Basa Basa Piri Pirimi midi din n yang yang lain lain :
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12/11/2014
Terdiri dari :
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12/11/2014
Jenis : Nama tergantung pada basanya dan jumlah fosfat yang dimiliki Adenin Guanin Sitosin Timin Urasil
AMP, ADP, ATP, dAMP, dADP, dATP GMP, GDP, GTP, dGMP, dGDP, dGTP CMP, CDP, CTP, dCTP, dCDP, dCTP TMP, TDP, TTP, UMP, UDP, UTP, dUMP, dUDP, dUTP
Fungsi Biokimiawi : 1. Reaksi pemindahan fosfat pada ATP dan trifosfat lainnya lainnya seperti UDP-GLUK UDP-GLUKOSA OSA dan UDP-GALAKTOSA 2. Sebagai koenzim koenzim yaitu : NAD, FAD FAD,, dll
3. Senyawa analognya analognya dibuat dibuat secara sintetik sintetik untuk terapi terapi 4. Unsur pembangun pembangun untuk asam nukleat yaitu RNA dan
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12/11/2014
Basa (Purin/Pirimidin) (+ Gula) Nukleosida (Basa Purin / Pirimidin Pirimidin + Gula) (+ Fosfat) Nukleotida
(Basa Purin / Pirimidin + Gula + Fosfat)
(+ nukleotida nukleotida-nukleotida) -nukleotida)
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12/11/2014
1. Kons Konsum umsi si nu nukl kleo eoti tida da manusi manusia a keb kebanya anyaka kan n dalam dalam bentu bentuk k nukleoprotein 2. Manu Manusi sia a mamp mampu u me mens nsin inttesis esis nu nukl kleo eoti tida da seca secara ra de novo novo (Hampir semua organisme mampu mensintesis nukleotida dr prek prekur urso sorr yg lebi lebih h sede sederh rhan ana a ja jalur de novo untuk nukleotida) 3. Nukl Nukleo eottida ida ju juga ga dap dapat disi disin ntesis sis dar dari hasil asil peme pemeca cah han nukleotida yang telah ada melalui salvage pathway (recycle) yaitu dari degradasi pirimidin dan purin, dari sel yang mati (regenerasi regenerasi)) atau dari makanan. dari makanan.
Di dalam usus halus terjadi pemutusan ikatan fosfodiester oleh endonuklease (pankreas) menjadi oligonukleotida menjadi oligonukleotida Dipecah lebih lanjut dg fosfodiesterase (enzim exonuclease non spesifik) menjadi monofosfat menjadi monofosfat
•
•
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12/11/2014
A N A B
Reaksi : 1. Pembe embentu ntukan kan Fosfo Fosforibo ribosil sil Pir Piro o Fosfat (PRPP)
O L I
ATP
AMP
RIBOSA-5-P
5-FOSFORIBOSIL-1-PIRO FOSFAT FOSFAT (PRPP)
PRPP PRP P - SI NTASE
S M E
P U R I N
A N A
2. Pe Pembentukan mbentukan 5-fosfo-b-ribosilamin
B
GLUTAMIN
GLUTAMAT
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12/11/2014
A N A
4. Pembentukan Pembentukan Formil Glisin Glisin Amida Ribosil Fosfat (FGAR)
B
Metenil-tetra hidr hi dro o fol folat at
O L
Tetra hidro fola folatt
I S
GAR GAR FORMI L TRANSFE TRANSFE RAS RASE E
FORMIL GLISIN AMI-DA RIBOSIL FOSFAT ( FGAR FGAR ))
M E
P
5. Pembentukan Pembentukan Formil Glisin Glisin Amidin ribosil fosfat fosfat GLUTAMIN
U
GLUTAMAT
R I N
FGAR
FORMIL GLISIN AMIDIN AM IDIN RIBOSIL RIB OSIL FOSFA FOSFAT ATP
ADP
A N A B
6. Pe Pembentukan mbentukan Amino Imidazolri-Bosil-5-Fosfat
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12/11/2014
A N A
8. Pembentukan Pembentukan Amino Imidazol Suksinil Karboksi Ribosil-5 P
B O L
H2O
AMINO IMIDAZOL SUKSINIL KARBOKSI RIBOSIL-5-P
AMINO IMIDAZOL IM IDAZOL
I S
KARBOKSIAMIDA RIBOSIL-5 P ASPARTAT
M E
9. Pembentukan Pembentukan Amino Imidazol Karboksiamida Ribosil-5 P
P U R I
AMINO IMIDAZOL IM IDAZOL SUKSINIL KARBOKSI RIBOSIL5-P
AMINO IMIDAZOL KARBOK SIAMIDA RIBOSIL-5-P FUMARAT
N
A N
10. Pembentuka Pembentukan n Formimido Imidazol Arboksiamida Ribosil-5 Ribosil-5 P
A B
N10Formil tetra
Tetra hidro
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12/11/2014
A N
12. Pembe Pembentukan ntukan AMP dan dan GMP GMP
A B O
ADENI LO SUKSINASE SUKSINASE
L
IMP
I
NAD+
S
ADENILO SUKSINAT ( AMPS )
H2O
M E
AM PS PS-S -SII NTASE
NADH + H+
P
I M PP-DEHI DEHI DRO DROGENAS GENASE E
GLUTAMAT GLUTAMIN
( XMP )
R
MONO PHOSPHAT )
XANTOSIN MONO FOSFAT
U
AMP (ADENOSIN
ATP
GUANOSIN MONO PHOSPHAT PHOSP HAT ( G M P )
I N
A N
Senyawa / Obat yang menghambat sintesis Purin :
A B
•
Anti Folat (Hidro folat)
Reaksi 4 (Tetra (Tetra hidro folat)
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12/11/2014
K A T A
Adenosin deaminase
Purin nukleosida fosforilase
Purin nukleosid nukleosida a oksidase
Guanase
B O L I S M E
P U R I N
Xantin oksidase
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12/11/2014
A N
3. Pe Pembentukan mbentukan Asam dehidro orotat
A B
KARBAMOIL-ASPARTAT
DEH I DRO OROT OROTASE ASE
AS. DEHIDRO OROTAT
( DHOA )
O L I
4. Pem Pembentukan bentukan Asam orotat
S M
AS. DEHIDRO DEHID RO OROTAT + NAD+
DEH I DRO DROGENAS GENASE E
ASAM OROTAT
E
P I R I M I
D I N
5. Pe Pembentukan mbentukan Orotidin Monofo Monofosfat sfat OROTAT ORO TAT FOSFO RI BOS BOSII L TRANSFERASE
ASAM OROTAT OROTAT + PRPP
OROTIDIN MONOFOSFAT( MONOFOSFAT( OMP )
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12/11/2014
K A T
SITOSIN
A
NH3
B O L
TIMIN
URASIL
DIHIDROTIMIN NADPH + H+
I S M
NADP+ DIHIDROURASIL
β-URIDOISOBUTIRAT
E
H2O
P I
ASAM UREIDOPROPIONAT
R I
H2O
ALANIN
M
β- AMINO BUTIRA BUTIRAT T
I D I N
CO2
+ NH3
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12/11/2014
K E
L
Gangguan metabolisme Purin :
A I
•
Gout
•
Hiperurikemia
•
Sindrom Lesch – Nyhan
•
Sindrom Kelley-Seegmiller
•
Penyakit Von Gierke
•
Hipourisemia
N A N
M
E T .
P U R
I N
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12/11/2014
K E
L A I N A N
M
E T .
P U R
I N
Penyakit Gout
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12/11/2014
K E
L A I N A
KELAINA INAN KL KLINIS INIS
ENZI NZIM YANG CACAT
KARAKTERISTIK KELAINAN KLINIS INIS
POLA PEW PEWA ARISA ISAN
GOUT OUT
PRPP PRPP SINT INTASE ASE
OVE OVER PROD PRODU UKSI & OVE OVER SEKRE EKRES SI PURI PURIN N
RES RESESIF - TERK TERKAI AIT TX
GOUT
PRPP SINTASE
OVER PRODUKSI & OVER SEKRESI PURIN
RESESIF - TERKAIT X
GOUT
PRPP SINTASE
OVER PRODUKSI & OVER SEKRESI PURIN
KEMUNGKINAN RESESIF X
GOUT
PRPP SINTASE
OVER PRODUKSI & OVER SEKRESI PURIN
RESESIF - TERKAIT X
SINDROM LESCH NYHAN
HGPR HGPRTT-AS ASE E
OVER OVER PROD PRODUK UKSI SI & OVER OVER SEKR SEKRES ESII PURI PURIN N; SELF MUTA-TION
RESESIF - TERKAIT X
DEFI DEFISI SINS NSII IMUN IMUN
ADEN ADENOS OSIN IN DEDE-
IMUNO DOFISIENSI KOMBINASI ( SEL T & B ) RESESIF -
N
M
E T .
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12/11/2014
•
•
•
•
Purin terdapat pada tubuh kita dan dijumpai di semua makanan dari sel hidup Pria lebih sering terserang asam urat daripada wanita Pemeriksaan asam urat dapat dilakukan pada serum atau plasma heparin, maupun urin. Pengukuran menggunakan alat digital atau metode kolorimetri
