METABOLISME PROTEIN Prasetyastuti Depart. Of Biochemistry GADJAH MADA UNIVERSITY

BIOSYNTHESIS NON-ESSENTIAL AMINO ACID CATABOLISM N - AMINO ACID CATABOLISM C – AMINO ACID CONVERTION AMINO ACID TO SPECIALIZED PRODUCTS

Naturally amino acids : 300 Amino acids in protein : 20 INTRODUCTION Naturally amino acids : 300 Amino acids in protein : 20 essential non-essential Arg* Ala His* Asp, Asn Ile Glu, Gln Leu Cys(*) Lys Gly Met Hyp Phe HyL(**) Thr Pro Trp Ser Val Tyr(**) (**) from essential AA

Grains : poor essential amino acid Animal : >> essential amino acid Egg = 1 (complete essential amino acids) Kwashiorkor : protein deficient Marasmus : protein & caloric deficients Essential amino acid : number enzyme to synthesize large relative than non-essential amino acids (manufacture “easy” amino acids)

BIOSINTESIS ASAM AMINO NON ESSENSIAL

1. Glutamat

2. Glutamin

3. Alanin

4. Aspartat & Asparagin

5. Serin

6. Glisin a. dari kolin

b. dari serin

7. Prolin

8. Sistein

9. Tyrosin

10. Hidroksi Prolin & Hidroksi Lisin

KATABOLISME PROTEIN & NITROGEN ASAM AMINO Kepentimgan Biomedis - dewasa normal : Intake Nitrogen sesuai dg N yg diekskresikan Balance N (-) : cancer, kwasiorkor,marasmus Balance N (+) : masa pertumbuhan, pregnansi Amonia berasal dr N α NH2 asam amino : toxic Dlm jar : nitrogen amide glutamin : non toxic

Di hepar: glutamin , deaminasi  amonia - urea (non toxic) Fs hepar terganggu(sirosis/hepatitis)- [amonia ]darah meningkat Turn over protein 1-2% /hari dari protein tubuh total Dari 75 -80% digunakan untuk sintesis protein baru 20-25% membentuk urea

Degradasi protein dinyatakan dengan t1/2 : waktu yang diperlukan untuk mereduksi kadarnya menjadi 50% dari nilai awalnya. T1/2 protein hepar < 30 menit- > 150 jam Protein dg t1/2 pendek : prolin, glutamin, serin, treonin T ½ 100 jam : aldolase, laktat Dh, sitokrom Kelebihan asam amino tidak disimpan tp di degradasi Kebutuhan protein orang dewasa : 30-60 g/hari

Ikatan peptid --- melepas peptid---- as. am. Bebas protease peptidase Ik. Internal ----- peptida yang lebih pendek endopeptidase Amino peptidase : mengeluarkan as. am. yg berasal dari amino terminal Karboksi peptidase : mengeluarkan as. am. yg berasal dari karbok sil terminal

Nitrogen diekskresi sebagai amonia, asam urat, urea Ikan (hidup di air) : amonotelik mengekskresi amonia Burung : urikotelik : mengekskresi asam urat Hewan darat, manusia: ureotelik mengekskresi urea [urea] darah , pada penderita peny. Ginjal, suatu akibat bukan penyebab gangguan fs ginjal

Biosintesis Urea 1. transaminasi 2. deaminasi oksidatif glutamat 3. transport amonia 4. siklus urea

Transaminasi

Alanin amino transferase I: & glutamat amino transferase II: mengkatalisis gugus amino ke piruvat membentuk alanin/α- ketoglutarat piruvat α as.amino α- KG α as. Amino I II alanin α as.keto glutamat α as.keto

Oxidative deamination catalyzed by L-amino acid oxidase (L-α-amino acid:O2 oxidoreductase). The α-imino acid

The glutamine synthase reaction strongly favors glutamine synthesis

The glutaminase reaction proceeds essentially irreversibly in the direction of glutamate and NH4+ formation. Note that the amide nitrogen, not the α-amino nitrogen, is removed.

Reaksi dan intermediet biosintesis urea

KATABOLISME CARBON SKELETON ASAM AMINO

Amphibolic intermediates formed from the carbon skeletons of amino acids.

Catabolism of L-asparagine (top) and of L-glutamine (bottom) to amphibolic intermediates

KATABOLISME PROLIN

Katabolisme Histidin & alfa ketoglutarat

Interconversion of serine and glycine catalyzed by serine hydroxymethyltransferase. (H4 folate,tetrahydrofolate.)

Reversible cleavage of glycine by the mitochondrial glycine synthase complex. (PLP, pyridoxalphosphate.)

Reaksi sistin reduktase

Catabolism of L-cysteine via the cysteine sulfinate pathway (top) and by the 3-mercaptopyruvate pathway (bottom).

Mixed disulfide of cysteine and homocysteine

Perubahan treonin menjadi glisin & asetil KoA

Intermediates in L-hydroxyproline catabolism Intermediates in L-hydroxyproline catabolism. (α-KA, α-keto acid; α-AA, α-amino acid.) Numerals identify sites of metabolic defects in 1 hyperhydroxyprolinemia and 2 type II hyperprolinemia.

Intermediet katabolisme tirosin

Alternative pathways of phenylalanine catabolism in phenylketonuria Alternative pathways of phenylalanine catabolism in phenylketonuria. The reactions also occur in normal liver tissue but are of minor significance

Katabolisme lisin

Katabolisme triptofan

Pembentukan xanturenat pada defisiensi vitamin B6

Formation of S-adenosylmethionine Formation of S-adenosylmethionine. ~CH3 represents the high group transfer potential of “active methionine.”

Perubahan metionin menjadi propionil KoA

The analogous first three reactions in the catabolism of leucine, valine, and soleucine. Note also the analogy of reactions 2 and 3 to reactions of the catabolism of fatty acid

Catabolism of the β-methylcrotonyl- CoA formed from L-leucine Catabolism of the β-methylcrotonyl- CoA formed from L-leucine. Asterisks indicate carbon atoms derived from CO2.

Subsequent catabolism of the tiglyl- CoA formed from L-isoleucine.

Subsequent catabolism of the methacrylyl-CoA formed from L-valine (see Figure 30–19). (α-KA, α-keto acid; α-AA, α-amino acid.)

PERUBAHAN ASAM AMINO MENJADI PRODUK KHUSUS Glisin - metabolit & produk farmasi diekskresi sbg konjugat glisin larut air  asam glikokolat  asam hipurat : dibentuk dr bensoat (bhn mkn aditive) Obat2an, metabolit obat, seny lain dg gugus karboksil - diekskresi dlm urin sbg konjugat glisin PERUBAHAN ASAM AMINO MENJADI PRODUK KHUSUS

Biosintesis hipurat

Β-Alanin - metabolit sistein , terdapat dlm KoA Sebagai - alanil (carnosin) Jar mamalia : membentuk - alanin drv sitosin, karnosin & anserin transaminasi - alanin - malonat semiald Gangguan metab hiperbeta-alaninemia -- [ - alanin, taurin, - NH2 isobutirat ] dlm jaringan & C tubuh meningkat

- alanil dipeptid Carnosin, & anserin mengaktivasi miosin ATPase, mengkelat Cu & meningkatkan ambilan Cu Biosintesis carnosin dikatalisis oleh carnosin sintetase melalui 2 tahap - pembentukan asil –adenilat - alanin terikat enzim - transfer alanil ke histidin

-alanil –AMP ATP + - alanin - -alanil –AMP + PPi -alanil –AMP + histidin  karnosin + AMP Hidrolisis carnosin ke -alanin & histidin dikatalisis oleh carnosinase Carnosinuria : def carnosin & turunannya -alanil –AMP

Homocarnosin Kadarnya dlm otak manusia > [carnosin] Disintesis dlm jar otak oleh carnosin sintetase Dlm serum, tdk menghidrolisis homocarnosin Homocarnosinosis - kelainan genetik - dihub kan dg perkembangan paraplegia spastic & retardasi mental

- fosforilasi & defosforilasi residu seril, treonil & tirosil mengatur aktivitas enzim tertentu metab KH & L

* Metionin: S-adenosil metionin

* Sistein - prekursor bag thioetanolamin CoA & taurin yg berkonjugasi dg asam empedu (as taurokolat)

Histidin dekarboksilasi histidin ----- histamin Dikatalisis oleh dekarboksilase (antihipertensi -aktivitasnya dihambat oleh α CH3 asam amino -mengkatalisis de-CO2 DOPA,5OH trp,phe,tyr,trp Dlm tubuh sbg: - ergothionein - carnosin -anserin

Ornithin & arginin - donor formimidin utk sintesis creatin Melalui ornitin  putresin, spermin & spermidin Arginin -prekursor NO yg bekerja sbg neurotransmiter relaxan otot polos vasodilator Sintesis NO dikatalisis oleh NO sintase , tgt NADPH dr arginin + O2 menghasilkan citrulin +NO

Metabolisme arginin, ornitin & prolin

Poliamin -spermidin & spermin berfungsi dlm: - proliferasi & pertumbuhan - faktor pertumbuhan sel mamalia yg dikultur - menstabilkan sel utuh, organela sub seluler & membran Dosis farmakologis poliamin adalah hipotermik & hipotensif

Triptophan Hidroksilasi trp  5-OH trp, dekarboksilasi --- serotonin (vasokonstriktor, stimulator kontraksi otot polos Katab serotonin - 5-OH indolasetat Mrpk rks deaminasi oxidative oleh monoamin Oksidase Sel tumor  produksi serotonin >>>

Di ginjal, hepar, Trp --- triptamin -- indolasetat Katabolit utama trp dlm urin normal : - indol 3-asetat - 5-OH indolasetat

CATABOLISM CARBON AMINO ACID Glycogenic Ketogenic Glycogenic & Ketogenic Ala Gly His Arg Hyp Met Asp Pro Ser Cys Thr Val Glu Leu Ile Lys Phe Trp Tyr