metabolisme asam amino
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Metabolisme Asam Amino
dr. Subandrate, M.Biomed
Bagian Biokimia dan Kimia MedikFK UNSRI
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PendahuluanMetabolisme:
Anabolisme Pembentukan, energi (+)Katabolisme Pemecahan, energi (-)
Asam AminoGugus Amino dan Karboksil pada atom C-α
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OVERVIEW METABOLISME ASAM AMINO
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A m in o A c id R e q u ir e m e n t s o f H u m a n s - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N u t r i t io n a l ly E s s e n t ia l N u t r i t io n a l ly N o n e s s e n t ia l - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
A r g in in e a A la n i n e H is t id i n e A s p a r a g i n e I s o le u c in e A s p a r ta te L e u c in e C y s te i n e L y s i n e G lu ta m a te M e th io n in e G lu ta m i n e P h e n y la la n i n e G l y c i n e T h r e o n in e P r o l in e T r y p to p h a n S e r in e V a l in e T y r o s in e
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - a “ N u tr i t io n a l l y s e m ie s s e n t ia l .” S y n t h e s iz e d a t r a te s in a d e q u a te to s u p p o r t g r o w t h o f c h i ld r e n .
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Biosintesis Asam Amino Non-EsensialTransaminasi:
Amino acid1 +a-Keto acid2 Amino acid2 +a-Keto acid1
Contoh:
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Prekursor Biosintesis Senyawa
Intermediet pada Glikolisis, Siklus Kreb’s, HMP-Shunt
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Transaminase Penting secara Klinik
Dapat digunakan menilai kerusakan hati dan jantung
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Katabolisme Rangka Karbon Asam AminoPenguraian Protein:
ProteasePeptidaseDalam Lisosom
Tergantung T1/2 (30 menit – 150 jam) T1/2 tiap protein berbeda-beda, tergantung
peranProtein Umum: > 100 jamProtein regulator: 30-120 menit
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Katabolisme Rangka Karbon Asam AminoAsam Amino Glukogenik α -
ketoglutarate, pyruvate, oxaloacetate, fumarate, atau succinyl CoA:Aspartate -AsparagineArginine -FenilalaninTyrosine -IsoleucineMethionine -ValineGlutamine -GlutamateProline -HistidineAlanine -SerineCysteine -GlycineThreonine -Tryptophan
• Asam Amino Ketogenik Acetyl CoA atau Acetoacetate:- Isoleucine- Leucine- Threonine- Tryptophan- Lysine- Phenylalanine- Tyrosine
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Katabolisme Rangka Karbon Asam Amino
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Asam Amino Glukogenik
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Katabolisme Asam Amino Menjadi Produk Khusus
Pembentukan senyawa Poliamin:Prolin glutamat semialdehid ornitin putresin spermidin spermin
Peran Poliamin: Proliferasi dan pertumbuhan sel
Pembentukan SAM:Metionin Homosistein S-adenosilmetionin Sumber donor metil penting untuk berbagai
reaksi dalam tubuhPembentukan Epinefrin
Tirosin DOPA dopamin Norepinefrin epinefrin
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Biosintesis UreaAmonia dihasilkan bakteri usus diabsorpsi oleh usus v porta hati dikonversi menjadi urea
Normal kadar amonia adalah 10 – 20 g/dLAmonia : senyawa toksik utk sistem saraf. Bila terjadi
kegagalan fungsi hati intoksikasi amonia : tremor, slurred speech, pandangan kabur, koma kematian
Mekanisme (Otak): Amonia berikatan dg alfa ketoglutarat glutamat. Akibatnya otak kehabisan alfa-ketoglutarat yg penting pada siklus Krebs. Hal ini menyebabkan kegagalan siklus Krebs/ TCA yg penting untuk memproduksi ekivalen pereduksi (NADH dan FADH2) yg dpt menghasilkan ATP di rantai respirasi mitokondria. kekurangan produksi energi.
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Biosintesis Urea
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Siklus UreaSebagian besar (80%) terjadi di sel hati1. NH3 + CO2 karbamoil fosfat (karbamoil
sintase)2. karbamoil fosfat + ornitin sitrulin (ornitin
transkarbamoilase)3. sitrulin + aspartat argininosuksinat
(argininosuksinat sintase)4. argininosuksinat L-arginin + fumarat
(argininosuksinase)5. L-arginin ornitin + urea (arginase)
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Biosintesis Urea
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Biosintesis Urea
Regulasi sintesis urea:Fungsi: membuang amonia yg toksikSiklus tetap berputar bahkan selama defisien
protein, peningkatan lemak/ KHKecepatan reaksi diatur oleh
Gross control: perubahan jumlah enzimFine control : sintesis karbamoil fosfat / N-Ac
glutamat. Arginin merupakan aktivator N-Ac glutamat sintase
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Vitamin dalam Metabolisme Asam AminoVitamin B-6 (pyridoxal phosphate)Folic acid (tetrahydrofolate)Vitamin B-12
Pada jalur? Asam amino?
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Keterkaitan Antarorgan
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Penyakit Terkait Metab. Asam AminoHomosisteinuria: Defisiensi enzim pembentuk
sistein. Penumpukan homosistein. Defek genetik.
Fenilketonuria: Kegagalan pembentukan tirosin dari fenilalanin karena gangguan enzim Fenilalanin hidroksilase
Maple Syrup Urine Disease: Penumpukan BCAA dan BC alpha-keto acid karena defisiensi branched-chain α-keto acid dehydrogenase
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Homosistein
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Fenilalanin
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valine isoleucine leucine
a-ketoglutarate glutamate (transamination)
a-ketoisovalerate a-keto-b-methylbutyrate a-ketoisokaproate
oxidative decarboxylationDehydrogenase of a-keto acids*
CO2
NAD+
NADH + H+
isobutyryl CoA a-methylbutyryl CoA isovaleryl CoA
Dehydrogenation etc., similar to fatty acid b-oxidation
propionyl CoA acetyl CoA
acetoacetate
acetyl CoA
propionyl CoA+ +
BCAA
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Senyawa NPN
NH3+NH2
H2N=C-HNCH2CH2CH2CHCO 2-
+NH3+
NH2CONHCH2CH2CH2CHCO2-
NO
Nitric oxide synthase (NOS)
Argininsitrulin+
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Nitrat OksidaCell messenger Implicated in a wide range of physiological and pathophysiological events: Vasodilation:
Activates guanylyl cyclase cGMP Nitroglycerin Glycerin + NO Sildenafil (Viagra): in vascular smooth muscle: blocking
fosfodiesterase 5
fosfodiesterase 5 cGMP GMP
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Keseimbangan NitrogenN positif (sintesis > katabolisme) mis. pertumbuhan,
penyembuhan,hamilN seimbang (sintesis =
katabolisme) mis. dewasa normal, sehatN negatif (sintesis < katabolisme) mis. kelaparan, sakit
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TERIMA
KASIH