Metabolisme Protein & Pengendalian Metabolisme

Pendahuluan Hubungan katabolisme & anabolisme protein, Lipid & Karbohidrat Siklus Nitrogen: Fiksasi Nitrogen Sistem enzim: nitrogenase & nitrogenase reduktase N2 + 8e- + 16ATP + 16H2O -> 2NH3 + H2 + 16ADP + 16 Pi + 8 H+ (Klebsiella pneumoniae) Penggunaan Amonia Fosfatidilserin These include some free-living soil bacteria, such as Klebsiella and Azotobacter, cyanobacteria, and Rhizobium, which is a symbiont on the roots of leguminous plants. The infecting bacterium assumes a modified form, called a bacteroid, inside the cells of infected plants. In root nodules of plants, the anaerobic environment is provided by the protein leghemoglobin, which binds any O2 that makes its way into the nodules.

Katabolisme Protein sumber asam amino dalam mamalia protein dari diet Protein dalam tubuh waktu paruh protein ubiquitinasi

Degradasi asam amino

Hubungan katabolisme protein dengan TCA Metabolisme Ser, Gly, Thr Dikatalisis oleh enzim Serine threonine dehydratase

Pemindahan gugus amin Transaminase: Deaminasi: glutamat dehidrogenase pemindahan gugus amin, biasanya glutamat, kepada asam -Keto. Macamnya: SGPT, SGOT Deaminasi: glutamat dehidrogenase Deaminasi oksidatif: glutamin synthetase asparagin synthetase

Transaminasi SGPT SGOT Memerlukan koenzim Vit B6, piridoksal fosfat (PyP) juga merupakan koenzim untuk enzim2 rasemisasi, dekarboksilasi dan modifikasi rantai samping asam amino. All known reactions of PyP-containing enzymes can be described mechanistically in the same way-formation of a planar Schiff base or aldimine intermediate, followed by formation of a resonance-stabilized carbanion with a quinoid structure, as shown in Figure 20.15. Depending on the bond labilized, formation of the aldimine can lead to a transamination (as shown in Figure 20.15), to decarboxylation, to racemization, or to numerous side chain modifications.

Detoksifikasi amonia Transport amonia: Siklus Urea: Ke hati untuk sintesis urea Siklus Urea: salah satu cara penghilangan amonia hanya dimiliki oleh organisme ureotelik sintesis arginin dari ornitin

Siklus Urea

Biosintesis asam amino Asam amino yang masuk lewat seny. antara pada TCA Konversi terjadi melalui transaminasi, deaminasi, dekarboksilasi dll Asam amino yang mengandung sulfur Diawali dengan terbentuknya PAPS (3’phosphoadenosin-5’-phosphosulfate) Biosintesis sistein dan metionin (tanaman & bakteri) Biosintesis sistein pada hewan Metionin  sistation  sistein defek Asam amino aromatik (phe,…) & his Jalur sikimat : Tahap 1 dan tahap 2 Ames test: His operon  carcinogenic comp. Sintesis a.a aromatik (phe, tyr, trp) & his melalui jalur sikimat The Ames test, which is used to search for mutagens (substances causing mutations) in the environment, is based on the histidine operon. In the test, bacteria with a mutation that disables the operon from making functional histidine pathway enzymes (auxotrophic bacteria) are treated with a suspected mutagen. The mutation rate can be easily assayed by counting the number of bacteria that mutate to being able to make histidine (prototrophs). This is done quite simply by plating the treated bacteria onto a medium lacking histidine. Only bacteria that have mutated and regained the ability to synthesize histidine will grow on the medium without histidine. There is a very high correlation between the compounds known to be carcinogenic in animals and those found to be mutagens in the Ames test. Thus, the Ames test provides a quick and inexpensive way to search for suspectted carcinogens in the environment.

sikimat

Asam amino dan neurotransmitter metabolit Gly, glu GABA His Histamin Tyr Katekolamines (epinefrin, norepinefrin, dopamin) Cholinergic synapses Nicotinic acetylcholine receptor Adrenergic Receptor  katekolamins 1. Choline + Acetyl-CoA <=> Acetylcholine + CoASH (dikatalisis oleh Choline Acetyltransferase) 2. Acetylcholine + H2O <=> Choline + Acetate (dikatalisis oleh Acetylcholinesterase)

PENGENDALIAN METABOLISME Pengendalian aktivitas enzim inhibisi balik (feed back inhibiton) -- enzim allosterik Glutamin synthetase : inh. Allosterik: his, trp, G-6P, karbamoil fosfat, CTP, AMP or Ala, Gly Modifikasi kovalen Kompartementasi Pengendalian konsentrasi enzim: induktif konstitutif Pengendalian oleh kerja Hormon: Contoh: insulin, glukagon - ada hirarkhi jumlah & waktu paruh rendah - lokasi produksi  efek. Glutamin sintetase merupakan enzim kunci untuk metabolisme asam amino. Di E.coli enzim ini merupakan dodekamer (12 subunit identik) dengan MW ~ 600 rb dalton. Gugus amida dari glutamat berguna untuk pembentukan asam-asam amino lain, nukleotida purin dan pirimidin, gula-gula amina. Di hewan, enzim ini berperan dalam detoksifikasi amonia, terutama di otak dan pada ekskresi amonia di ginjal. Jika jumlah glutamat dan glutamin menumpuk, akan mengurangi kadar a-ketoglutarat yang merupakan senyawa antara dalam jalur TCA. Karena itu enzim ini harus sangat dikendalikan. Mekanisme kendalinya: Inhibisi allosterik.  8 inhibitor: oleh metabolic end product (His, trp, G-P, karbamoil fosfat, CTP, AMP) atau indikator keadaan umum metabolisme asam amino (glisin dan alanin) Glutamine + HCO3- + 2ATP + H2O -> Carbamoyl Phosphate + 2 ADP + Pi + Glutamate

Pada tingkat apa expresi gen dikendalikan? Disemua tahap antara DNA & Protein mRNA tak aktif nucleus cytosol 5 Degradasi mRNA Pre- mRNA DNA mRNA mRNA 1 Pengendalian transkripsi 2 Pemrosesan RNA Aktivitas protein 6 3 Transport RNA 4 Pengendalian translasi Protein tak aktif subject to a wide variety of regulatory control protein

Jacob-Monod (1961)

Pengendalian positif & Negatif